Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The st...Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.展开更多
Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 d...Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.展开更多
Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and n...Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.展开更多
Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However...Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.展开更多
OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of ...OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of which is lost during the peri-transplantation period. RESULTS: The islet-cell isolation technique is perfected, but improvements are still progressing in two major directions: preservation of islet cells and tolerance induction. Optimum islet cell viability and function depends on appropriate revascularization of the islet graft and blockade of thrombus formation as well as cytokine and free radical release. Conditioning the islet cells in-vitro prior to transplantation to either upregulate VEGF expression or downregulate NF-kappa B transcription factor has proven to improve revascularization and to prevent islet cell apoptosis and cytokine-mediated damage. Tolerance induction is currently being best achieved by selecting and combining immunosuppressive agents such as monoclonal antibodies which target the major signaling molecules during immune activation, but which are least toxic to islet cells. CONCLUSIONS: Patients with insulin-dependent diabetes will greatly benefit from current developments in effective approaches to protect islets during the peritransplant period. Emerging interest in stem cell biology and differentiation may provide the ultimate solution to the problem of organ scarcity and islet cell protection from the peritransplant induced damage.展开更多
AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether th...AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.展开更多
AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by i...AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.展开更多
AIM： To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa （SIS）. METHODS： Pancreatic islets were isolated from Wistar rats by standard sur...AIM： To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa （SIS）. METHODS： Pancreatic islets were isolated from Wistar rats by standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and Euroficoll purification. Purified islets were cultured in plates coated with multilayer SIS （SIS-treated group） or without multilayer SIS （standard cultured group） for 7 and 14 d in standard islet culture media of RPMI 1640. After isolation and culture, islets from both experimental groups were stained with dithizone and counted. Recovery of islets was determined by the ratio of counts after the culture to the yield of islets immediately following islet isolation. Viability of islets after the culture was assessed by the glucose challenge best with low （2.7 mmol/L） and high glucose （16.7 mmol/L） solution supplemented with 50 mmol/L 3-isobutyl-1- methylxanthine （IBMX） solution. Apoptosis of islet cells after the culture was measured by relative quantification of histone-complexed DNA fragments using ELISA. RESULTS： After 7 or 14 d of in vitro tissue culture, the recovery of islets in SIS-treated group was significantly higher than that cultured in plates without SIS coating. The recovery of islets in SIS-treated group was about twice more than that of in the control group. In SIS treated group, there was no significant difference in the recovery of islets between short- and long-term periods of culture （95.8±1.0% vs 90.8±1.5%, P〉0.05）. When incubated with high glucose （16.7 mmol/L） solution, insulin secretion in SIS-treated group showed a higher increase than that in control group after 14 d of culture （20.7±1.1 mU/L vs 11.8±1.1 mU/L, P〈0.05）. When islets were placed in high glucose solution containing IBMX, stimulated insulin secretion was higher in SlS-treated group than in control group. Calculated stimulation index of SlS-treated group was about 23 times of control group. In addition, the stimulation index of SlS-treated group remained constant regardless of short- and long- term periods of culture （9.5±0.2 vs 10.2±1.2, P〉0.05）. Much less apoptosis of islet cells occurred in SlS-treated group than in control group after the culture. CONCLUSION： Co-culture of isolated rat islets with native sheet-like SIS might build an extracellular matrix for islets and provide possible biotrophic and growth factors that promote the recovery and subsequent function of islets.展开更多
Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with typ...Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.展开更多
To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric la...To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.展开更多
BACKGROUND: The ability to maintain isolated human islet preparation in tissue culture has recently been adopted by most islet transplant centers to improve the safety and practicality of islet transplantation. Howeve...BACKGROUND: The ability to maintain isolated human islet preparation in tissue culture has recently been adopted by most islet transplant centers to improve the safety and practicality of islet transplantation. However, maintaining islet viability and recovery remains a challenge in clinical setting. Extracellular matrix (ECM) is one of the most important components of islet microenvironment. The reconstruction of the cell-matrix relationship seems to be effective in improving the loss of differentiated islet structure and function. Small intestinal submucosa ( SIS ) , a naturally occurring ECM, has been investigated to be able to promote wound healing, tissue remodeling, and cell growth. The purpose of this study was to evaluate the recovery and function of isolated rat pancreatic islets after in vitro culture with SIS. METHODS: Pancreatic islets were isolated from Wistar rats by using standard surgical procurement followed by intra-ductal collagenase distension, mechanical dissociation, and EuroFicoll purification. Groups of purified islets were cultured in plates which were coated with multilayer SIS (SIS-treated group) or without ( standard cultured group) for 7 days and 14 days in standard islet culture conditions of RP-MI 1640 tissue culture media in humidified atmosphere containing 95% air and 5% CO2 at 37 ℃. The mean recovery of islets after the culture period was determined by sizing duplicate counts of a known volume and their viability was assessed by static incubation with low glucose (2.7 mmol) , high glucose (16.7 mmol) and high glucose solution supplemented with 50 μm 3-isobutyl-1-methylxanthine (IB-MX) solution. RESULTS: After 7 days and 14 days of in vitro tissue culture, the SIS-treated group showed a significantly higher recovery compared with those cultured under standard conditions. The recovery in the SIS-treated group was about two times of the control group cultured in standard conditions after 14 days culture. In the SIS-treated group, there was no statistically difference between the short and long periods of culture ( 95. 8 ± 1.0% vs. 90. 8±1. 5% , P 】 0.05). During incubation in high glucose (16.7 mmol) solution, there was a 2-3 fold increase in insulin secretion from both groups, but the SIS-treated group showed a higher increase than the standard cultured group after 14-day culture (20.7 ±1.1 mU/L vs. 11. 8 ±1.1 mU/L, P 【 0. 05). When islets were placed in the high glucose solution supplemented with IBMX, the stimulated insulin response in the SIS-treated group was higher than that in the standard cultured group in spite of the duration of the culture. The stimulation index of the SIS-treated group was about 2-3 times of the standard cultured group. In addition , after a long period of culture, the stimulation index of the SIS-treated group was statistically equivalent with that of the short period of culture (9.5 ±0.2 vs. 10.2 ±1.2, P】0.05). CONCLUSIONS: The co-culture of isolated rat islets with native sheet-like SIS can provide an excellent extracellular matrix, possible biotrophic and growth factors that promote the recovery and subsequent function of islets after in vitro tissue culture. In view of results of this study and rapid degradation of SIS in vitro, future studies will investigate the extended duration of culture and the effect of SIS on islets in vitro.展开更多
Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cro...Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cross-sectional study, 100 T2DM patients attending the Diabetic patients care Centre were recruited, thirty five patients were males and sixty five were females, the mean age of the patients was 50.29 ± 0.456 years, and body mass index (BMI) was 26.54 ± 0.437. We estimated β-cell function using fasting C-peptide levels;homeostatic model assessment for β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated from C-peptide and fasting blood glucose (FBG). Results: C-peptide was significantly and positively correlated with HOMA-B and HOMA-IR. FBG also showed significant negative correlation with HOMA-B, but was positively and significantly correlated with HOMA-IR. HbA1c was negatively and significantly correlated with HOMA-B. Patients with low C-peptide levels had increased FBG and HbA1c level, while patients with high C-peptide levels were having high HOMA-IR and HOMA-B. Conclusions: Fasting C-peptide is a useful marker of pancreatic β-cell function, and its circulating levels could be used to evaluate insulin secretion and insulin resistance. Moreover, HOMA-IR is an effective index to achieve glycemic control by appropriate pharmacologic treatment of T2DM.展开更多
β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line ora...β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.展开更多
Objective: To investigate the effect of Sig Leo Dean on serum ceramide, chemerin, islet function and oxidative stress index in type 2 diabetes mellitus (T2DM) rats. Methods: Fifty-four SPF male SD rats aged 4 weeks we...Objective: To investigate the effect of Sig Leo Dean on serum ceramide, chemerin, islet function and oxidative stress index in type 2 diabetes mellitus (T2DM) rats. Methods: Fifty-four SPF male SD rats aged 4 weeks were selected and randomly divided into blank group, model group and treatment group with 18 rats in each group. After feeding with high-fat and high-sugar diet for 6 weeks, the model group and treatment group were given intraperitoneal injection of streptozotocin (STZ) to establish the model of T2DM rats. After successful modeling, the treatment group was given cegliptine 10 mg/kg/d, and the blank group and model group were given the same amount of saline. After 6 weeks, the indicators were tested and compared. Results: Before the intervention, the model group and treatment group rat body weight, FPG, Fins and HOMA-IR were significantly higher than the blank group (P<0.05), model group and HOMA- beta treated rats were significantly lower than that of the control group (P<0.05);after the intervention, FPG, Fins and HOMA-IR were significantly higher than the control group in the treatment group but compared with model group (P<0.05), treatment group, body weight, HOMA- beta is significantly higher than model group but lower than that of the control group (P<0.05);before the intervention, the model group and the serum ceramide, the rats in the treatment group chemerin was significantly higher than that of control group (P<0.05);intervention, serum ceramide, chemerin significantly higher than the control group the treatment group but lower than that of model group (P<0.05);before the intervention, the model group and treatment group rats, the SOD level of GSH-PX was significantly lower than that of the control group (P<0.05);intervention treatment group SOD and GSH-PX Significantly lower than the blank group, but higher than the model group (P<0.05). Conclusion: Western medicine can significantly improve the islet function of T2DM model rats, reduce serum ceramide and chemerin levels, and improve the antioxidant function of rats.展开更多
目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加...目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加甘精胰岛素U300治疗,持续治疗3个月,对比2组血糖及相关指标变化,并监测患者胰岛素功能相关指标改善情况,评估低血糖反应等不良反应情况。结果治疗后,U300组血糖指标、血糖波动指标均显著低于非甘精组,差异有统计学意义(P<0.05)。U300组治疗后胰岛素功能指标均显著优于非甘精组,空腹及餐后2 h C肽均显著高于非甘精组,差异有统计学意义(P<0.05)。U300组低血糖反应发生率(2.50%,1/40)和不良反应总发生率(20.00%,8/40)与非甘精组(2.56,1/39;17.95%,7/39)比较,差异无统计学意义(P>0.05)。结论增加甘精胰岛素U300治疗,可更好地提升患者血糖管理效果,并可改善胰岛功能,有利于稳定控制血糖,有助于提高患者病情控制效果,应用效果安全可靠。展开更多
目的探讨2型糖尿病湿热困脾证合并血脂紊乱患者胰岛功能变化及其影响因素。方法选择2020年1月—2020年12月医院收治的2型糖尿病湿热困脾证患者100例,根据美国ATPIII评估标准将其分为血脂紊乱组62例与血脂正常组38例。比较各组SF-36积分...目的探讨2型糖尿病湿热困脾证合并血脂紊乱患者胰岛功能变化及其影响因素。方法选择2020年1月—2020年12月医院收治的2型糖尿病湿热困脾证患者100例,根据美国ATPIII评估标准将其分为血脂紊乱组62例与血脂正常组38例。比较各组SF-36积分、胰岛素分泌功能(Homeostasis model assessment-β,HOMA-β)、胰岛素抵抗水平(Homeostasis model assessment-IR,HOMA-IR)、胰岛素敏感指数(Insulin sensitivity index,ISI)、空腹C肽和空腹胰岛素。应用单因素和多因素分析法研究血脂异常的相关因素。结果高甘油三酯组与混合型高脂组空腹胰岛素水平显著高于高胆固醇组与血脂正常组,差异有统计学意义(P<0.05)。高甘油三酯组空腹C肽水平显著高于高胆固醇组,差异有统计学意义(P<0.05)。混合型高脂组与高甘油三酯组的ISI水平低于高胆固醇组(P<0.05)。高甘油三酯组HOMA-β水平明显高于高胆固醇组与血脂正常组,差异有统计学意义(P<0.05)。高甘油三酯组及混合型高脂组HOMA-IR水平显著高于高胆固醇组,差异有统计学意义(P<0.05)。两组患者在躯体疼痛、整体健康、活力、社会功能和精神健康维度方面比较,差异有统计学意义(P<0.01)。多因素Logistic分析显示,喜食油腻、吸烟史、腰围和空腹胰岛素是2型糖尿病湿热困脾证患者血脂异常的危险因素,有氧运动是2型糖尿病湿热困脾证患者血脂异常的保护因素(P<0.05)。结论不同血脂紊乱类型对胰岛功能的影响并不相同,应针对相关因素积极预防,降低胰岛分泌负担,促使胰岛功能恢复。展开更多
文摘Objective: The aim of this study is to investigate how individuals with type 2 diabetes mellitus’ pancreatic β-cell function index and insulin resistance index are affected by tuberculosis infection. Methods: The study group consisted of 89 patients with type 2 diabetes mellitus and tuberculosis infection who were admitted to Jingzhou Chest Hospital between March 2019 and March 2021. Gender and duration of diabetes were matching conditions. The control group was made up of 89 patients with type 2 diabetes who were admitted to Jingzhou Central Hospital’s endocrinology department during the same period. The two patient groups provided general information such as gender, age, length of diabetes, and blood biochemical indexes such as glycosylated hemoglobin (HbA1c), fasting glucose (FPG), and fasting C-peptide (FC-P). The HOMA calculator was used to calculate the HOMA-β and the HOMA-IR, and intergroup comparisons and correlation analyses were carried out. Results: Regarding gender, age, disease duration, FC-P, and HbA1c, the differences between the two groups were not statistically significant (P > 0.05). However, BMI, FPG, HOMA-β, and HOMA-IR showed statistically significant differences (P < 0.05). In comparison to the control group, the study group’s HOMA-β was lower and its HOMA-IR was greater. According to Spearman’s correlation analysis, HOMA-β had a negative association (P th FPG, HbA1c, and the length of the disease, and a positive correlation with BMI and FC-P. A positive correlation was found between HOMA-IR and BMI, FPG, and FC-P (P < 0.01), as well as a correlation with the length of the disease (P > 0.05) and HbA1c. Conclusions: In type 2 diabetes mellitus combined with tuberculosis infection, the patients had higher FPG levels and lower FC-P levels, the secretory function of pancreatic β-cells was more severely impaired, and insulin resistance was more obvious.
文摘Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
文摘Background and Objective:Self-monitoring of blood glucose(SMBG)is crucial for achieving a glycemic target and upholding blood glucose stability,both of which are the primary purpose of anti-diabetic treatments.However,the association between time in range(TIR),as assessed by SMBG,andβ-cell insulin secretion as well as insulin sensitivity remains unexplored.Therefore,this study aims to investigate the connections between TIR,derived from SMBG,and indices representingβ-cell functionality and insulin sensitivity.The primary objective of this study was to elucidate the relationship between short-term glycemic control(measured as points in range[PIR])and bothβ-cell function and insulin sensitivity.Methods:This cross-sectional study enrolled 472 hospitalized patients with type 2 diabetes mellitus(T2DM).To assessβ-cell secretion capacity,we employed the insulin secretion-sensitivity index-2(ISSI-2)and(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,while insulin sensitivity was evaluated using the Matsuda index and HOMA-IR.Since SMBG offers glucose data at specific point-in-time,we substituted TIR with PIR.According to clinical guidelines,values falling within the range of 3.9-10 mmol were considered"in range,"and the corresponding percentage was calculated as PIR.Results:We observed significant associations between higher PIR quartiles and increased ISSI-2,(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,Matsuda index(increased)and HOMA-IR(decreased)(all P<0.001).PIR exhibited positive correlations with log ISSI-2(r=0.361,P<0.001),log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index(r=0.482,P<0.001),and log Matsuda index(r=0.178,P<0.001)and negative correlations with log HOMA-IR(r=-0.288,P<0.001).Furthermore,PIR emerged as an independent risk factor for log ISSI-2,log(ΔC-peptide_(0-120)/Δglucose_(0-120))×Matsuda index,log Matsuda index,and log HOMA-IR.Conclusion:PIR can serve as a valuable tool for assessingβ-cell function and insulin sensitivity.
文摘OBJECTIVE: To review the current progress of islet cell transplantation in patients with insulin-dependent diabetes, emphasizing on the difficulties with recovering and preserving islet cell mass and function, 30% of which is lost during the peri-transplantation period. RESULTS: The islet-cell isolation technique is perfected, but improvements are still progressing in two major directions: preservation of islet cells and tolerance induction. Optimum islet cell viability and function depends on appropriate revascularization of the islet graft and blockade of thrombus formation as well as cytokine and free radical release. Conditioning the islet cells in-vitro prior to transplantation to either upregulate VEGF expression or downregulate NF-kappa B transcription factor has proven to improve revascularization and to prevent islet cell apoptosis and cytokine-mediated damage. Tolerance induction is currently being best achieved by selecting and combining immunosuppressive agents such as monoclonal antibodies which target the major signaling molecules during immune activation, but which are least toxic to islet cells. CONCLUSIONS: Patients with insulin-dependent diabetes will greatly benefit from current developments in effective approaches to protect islets during the peritransplant period. Emerging interest in stem cell biology and differentiation may provide the ultimate solution to the problem of organ scarcity and islet cell protection from the peritransplant induced damage.
基金Supported by the Beijing Natural Science Foundation(No.7131007)National Basic Research Program of China(973 ProgramNo.2007CB512201)
文摘AIM： To investigate the relationship between insulin resistance （IR）/β-cell dysfunction and diabetic retinopathy （DR） in Chinese patients with type 2 diabetes mellitus （T2DM）, and to explore further whether there were differences in the relationship among diabetic patients with higher and lower body mass index （BMI）. METHODS： Cross-sectional study. A total of 1466 subjects with T2DM were recruited in a local Desheng Community of urban Beijing from November 2009 to June 2012 for the cohort of Beijing Desheng Diabetic Eye Study. Standardized evaluation was carried out for each participant, including questionnaire, ocular and anthropometric examinations, and laboratory tests. Seven fields 30° color fundus photographs were used for DR grading according to the Early Treatment Diabetic Retinopathy Study protocols. Homeostatis Model Assessment （HOMA） method was employed for IR and β-cell function assessment. RESULTS： After excluding those participants who were treated with insulin （n=352） or had missing data of fasting insulin （n=96）, and further excluding those with poor quality of retinal photographs （n=10）, a total of 1008 subjects were included for the final analysis, 406 （40.3%） were men and 602 （59.7%） were women, age ranging fiom 34 to 86 （64.87±8.28）y. Any DR （levels 14 and above） was present in 278 （27.6%） subjects. After adjusting for possible covariates, the presence of any DR did not correlate with HOMA IR [odds ratio （OR） 1.51, 95% confidence interval （Cl） 0.87-2.61, P=0.14] or HOMA β-cell （OR 0.71, 95%CI 0.40-1.26, P=0.25）. After stratification by BMI, the presence of any DR was associated positively with HOMA IR （OR 2.46, 95%CI： 1.18-5.12, P=0.016）, and negatively with HOMA β-cell （OR 0.40, 95%CI： 0.19-0.87, P=0.021） in the group of patients with higher BMI （225 kg/m2）. In the group of patients with lower BMI （〈25 kg/m2）, the presence of any DR was not associated with HOMA IR （OR 1.00, 95%C1： 0.43-2.33, P=I.00） or HOMA β-cell （OR 1.41, 95%CI： 0.60-3.32, P=0.43）. CONCLUSION： The data suggest that higher IR and lower 13-cell function are associated with the presence of DR in the subgroup of diabetic patients with higher BMI. However, this association is not statistically significant in diabetic patients with lower BMI.
基金Supported by the National Natural Science Foundation of China, No. 30571759Social Development Foundation of Shanghai, No. 200253
文摘AIM. To investigate the influence of heme oxygenase-1 （HO-1） gene transfer on the viability and function of cultured rat islets in vitro. METHODS： Islets were isolated from the pancreata of Sprague-Dawley rats by intraductal collagenase digestion, and purified by discontinuous Ficoll density gradient centrifugation. Purified rat islets were transfected with adenoviral vectors containing human HO-1 gene （Ad- HO-1） or enhanced green fluorescent protein gene （Ad- EGFP）, and then cultured for seven days. Transfection was confirmed by fluorescence microscopy and Western blot. Islet viability was evaluated by acridine orange/ propidium iodide fluorescent staining. Glucose-stimulated insulin release was detected using insulin radioimmunoassay kits and was used to assess the function of islets. Stimulation index （SI） was calculated by dividing the insulin release upon high glucose stimulation by the insulin release upon low glucose stimulation. RESULTS： After seven days culture, the viability of cultured rat islets decreased significantly （92% ± 6% vs 52% ± 13%, P 〈 0.05）, and glucose-stimulated insulin release also decreased significantly （6.47 ± 0.55 mIU/ L/30IEO vs 4.57 ± 0.40 mIU/L/3OIEO., 14.93 ± 1.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. Transfection of rat islets with adenoviral vectors at an 1±10 of 20 was efficient, and did not impair islet function. At 7 d post-transfection, the viability of Ad-HO-1 transfected islets was higher than that of control islets（71% ± 15% vs 52% ± 13%, P 〈 0.05）. There was no significant difference in insulin release upon low glucose stimulation （2.8 mmol/L） among Ad-HO-1 transfected group, Ad-EGFP transfected group, and control group （P 〉 0.05）, while when stimulated by high glucose （16.7 mmol/L） solution, insulin release in Ad-HO-1 transfected group was significantly higher than that in Ad-EGFP transfected group and control group, respectively （12.50 ±2.17 mIU/L/30IEQ vs 8.87 ± 0.65 mIU/L/30IEQ, 12.50 ± 2.17 mIU/L/30IEQ vs 9.63 ± 0.71 mIU/L/30IEQ, P 〈 0.05）. The SI of Ad-HO-1 transfected group was also significantly higher than that of Ad-EGFP transfected group and control group, respectively （2.21 ± 0.02 vs 2.08 ± 0.05; 2.21 ± 0.02 vs 2.11 ± 0.03, P 〈 0.05）. CONCLUSION： The viability and function of rat islets decrease over time in in vitro culture, and heine oxygenase-1 gene transfer could improve the viability and function of cultured rat islets.
基金Supported by the Key Program of Science and Technique of Ministry of Education of the People's Republic of China, No.104169
文摘AIM： To evaluate the recovery and function of isolated rat pancreatic islets during in vitro culture with small intestinal submucosa （SIS）. METHODS： Pancreatic islets were isolated from Wistar rats by standard surgical procurement followed by intraductal collagenase distension, mechanical dissociation and Euroficoll purification. Purified islets were cultured in plates coated with multilayer SIS （SIS-treated group） or without multilayer SIS （standard cultured group） for 7 and 14 d in standard islet culture media of RPMI 1640. After isolation and culture, islets from both experimental groups were stained with dithizone and counted. Recovery of islets was determined by the ratio of counts after the culture to the yield of islets immediately following islet isolation. Viability of islets after the culture was assessed by the glucose challenge best with low （2.7 mmol/L） and high glucose （16.7 mmol/L） solution supplemented with 50 mmol/L 3-isobutyl-1- methylxanthine （IBMX） solution. Apoptosis of islet cells after the culture was measured by relative quantification of histone-complexed DNA fragments using ELISA. RESULTS： After 7 or 14 d of in vitro tissue culture, the recovery of islets in SIS-treated group was significantly higher than that cultured in plates without SIS coating. The recovery of islets in SIS-treated group was about twice more than that of in the control group. In SIS treated group, there was no significant difference in the recovery of islets between short- and long-term periods of culture （95.8±1.0% vs 90.8±1.5%, P〉0.05）. When incubated with high glucose （16.7 mmol/L） solution, insulin secretion in SIS-treated group showed a higher increase than that in control group after 14 d of culture （20.7±1.1 mU/L vs 11.8±1.1 mU/L, P〈0.05）. When islets were placed in high glucose solution containing IBMX, stimulated insulin secretion was higher in SlS-treated group than in control group. Calculated stimulation index of SlS-treated group was about 23 times of control group. In addition, the stimulation index of SlS-treated group remained constant regardless of short- and long- term periods of culture （9.5±0.2 vs 10.2±1.2, P〉0.05）. Much less apoptosis of islet cells occurred in SlS-treated group than in control group after the culture. CONCLUSION： Co-culture of isolated rat islets with native sheet-like SIS might build an extracellular matrix for islets and provide possible biotrophic and growth factors that promote the recovery and subsequent function of islets.
文摘Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.
基金supported by a grant from the Provincial Natural Sciences Foundation of Hubei, China (No 2005ABA158)
文摘To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.
文摘BACKGROUND: The ability to maintain isolated human islet preparation in tissue culture has recently been adopted by most islet transplant centers to improve the safety and practicality of islet transplantation. However, maintaining islet viability and recovery remains a challenge in clinical setting. Extracellular matrix (ECM) is one of the most important components of islet microenvironment. The reconstruction of the cell-matrix relationship seems to be effective in improving the loss of differentiated islet structure and function. Small intestinal submucosa ( SIS ) , a naturally occurring ECM, has been investigated to be able to promote wound healing, tissue remodeling, and cell growth. The purpose of this study was to evaluate the recovery and function of isolated rat pancreatic islets after in vitro culture with SIS. METHODS: Pancreatic islets were isolated from Wistar rats by using standard surgical procurement followed by intra-ductal collagenase distension, mechanical dissociation, and EuroFicoll purification. Groups of purified islets were cultured in plates which were coated with multilayer SIS (SIS-treated group) or without ( standard cultured group) for 7 days and 14 days in standard islet culture conditions of RP-MI 1640 tissue culture media in humidified atmosphere containing 95% air and 5% CO2 at 37 ℃. The mean recovery of islets after the culture period was determined by sizing duplicate counts of a known volume and their viability was assessed by static incubation with low glucose (2.7 mmol) , high glucose (16.7 mmol) and high glucose solution supplemented with 50 μm 3-isobutyl-1-methylxanthine (IB-MX) solution. RESULTS: After 7 days and 14 days of in vitro tissue culture, the SIS-treated group showed a significantly higher recovery compared with those cultured under standard conditions. The recovery in the SIS-treated group was about two times of the control group cultured in standard conditions after 14 days culture. In the SIS-treated group, there was no statistically difference between the short and long periods of culture ( 95. 8 ± 1.0% vs. 90. 8±1. 5% , P 】 0.05). During incubation in high glucose (16.7 mmol) solution, there was a 2-3 fold increase in insulin secretion from both groups, but the SIS-treated group showed a higher increase than the standard cultured group after 14-day culture (20.7 ±1.1 mU/L vs. 11. 8 ±1.1 mU/L, P 【 0. 05). When islets were placed in the high glucose solution supplemented with IBMX, the stimulated insulin response in the SIS-treated group was higher than that in the standard cultured group in spite of the duration of the culture. The stimulation index of the SIS-treated group was about 2-3 times of the standard cultured group. In addition , after a long period of culture, the stimulation index of the SIS-treated group was statistically equivalent with that of the short period of culture (9.5 ±0.2 vs. 10.2 ±1.2, P】0.05). CONCLUSIONS: The co-culture of isolated rat islets with native sheet-like SIS can provide an excellent extracellular matrix, possible biotrophic and growth factors that promote the recovery and subsequent function of islets after in vitro tissue culture. In view of results of this study and rapid degradation of SIS in vitro, future studies will investigate the extended duration of culture and the effect of SIS on islets in vitro.
文摘Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cross-sectional study, 100 T2DM patients attending the Diabetic patients care Centre were recruited, thirty five patients were males and sixty five were females, the mean age of the patients was 50.29 ± 0.456 years, and body mass index (BMI) was 26.54 ± 0.437. We estimated β-cell function using fasting C-peptide levels;homeostatic model assessment for β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated from C-peptide and fasting blood glucose (FBG). Results: C-peptide was significantly and positively correlated with HOMA-B and HOMA-IR. FBG also showed significant negative correlation with HOMA-B, but was positively and significantly correlated with HOMA-IR. HbA1c was negatively and significantly correlated with HOMA-B. Patients with low C-peptide levels had increased FBG and HbA1c level, while patients with high C-peptide levels were having high HOMA-IR and HOMA-B. Conclusions: Fasting C-peptide is a useful marker of pancreatic β-cell function, and its circulating levels could be used to evaluate insulin secretion and insulin resistance. Moreover, HOMA-IR is an effective index to achieve glycemic control by appropriate pharmacologic treatment of T2DM.
文摘β-cell dysfunction and decreased insulin sensitivity are believed to be two chief mechanisms that participate in deterioration of glycemic control in Type 2 diabetes. Meformin is widely accepted as the first-line oral agent in the treatment of Type 2 diabetes. However, the relative contributions of improved β-cell function and increased insulin sensitivity to reduction in hemoglobin A1c (HbA1c) are unclear in newly diagnosed Type 2 diabetic patients treated with metformin. We investigated β-cell function and insulin sensitivity in relation to reduction in HbA1c in 20 newly diagnosed Type 2 diabetic patients (17 men and 3 women, mean age 49.1 ± 10.1 years, mean body mass index 26.4 ± 5.2 kg/m2) treated with metformin for 16 weeks. We used homeostasis model assessment (HOMA) 2%B and HOMA2%S as estimates of β-cell function and insulin sensitivity, respectively. Median HOMA2%B and HOMA2%S significantly increased from 38.8 to 68.8 (p p = 0.004), respectively. In univariate regression analysis, reduction in HbA1c was highly correlated with change in HOMA2%B (r = -0.866, p < 0.001), but not with that in HOMA2%S (r = -0.264, p = 0.260). Furthermore, multivariate regression analysis with reduction in HbA1c as a dependent variable showed that increase in HOMA2%B but not that in HOMA2%S was a significant dependent variable (β = -0.847, p β-cell function rather than increased insulin sensitivity is associated with reduction in HbA1c. These results suggest that metformin reduces HbA1c chiefly through improved β-cell function rather than increased insulin sensitivity in patients with newly diagnosed Type 2 diabetes.
基金National Natural Science Foundation of China(8157040265).
文摘Objective: To investigate the effect of Sig Leo Dean on serum ceramide, chemerin, islet function and oxidative stress index in type 2 diabetes mellitus (T2DM) rats. Methods: Fifty-four SPF male SD rats aged 4 weeks were selected and randomly divided into blank group, model group and treatment group with 18 rats in each group. After feeding with high-fat and high-sugar diet for 6 weeks, the model group and treatment group were given intraperitoneal injection of streptozotocin (STZ) to establish the model of T2DM rats. After successful modeling, the treatment group was given cegliptine 10 mg/kg/d, and the blank group and model group were given the same amount of saline. After 6 weeks, the indicators were tested and compared. Results: Before the intervention, the model group and treatment group rat body weight, FPG, Fins and HOMA-IR were significantly higher than the blank group (P<0.05), model group and HOMA- beta treated rats were significantly lower than that of the control group (P<0.05);after the intervention, FPG, Fins and HOMA-IR were significantly higher than the control group in the treatment group but compared with model group (P<0.05), treatment group, body weight, HOMA- beta is significantly higher than model group but lower than that of the control group (P<0.05);before the intervention, the model group and the serum ceramide, the rats in the treatment group chemerin was significantly higher than that of control group (P<0.05);intervention, serum ceramide, chemerin significantly higher than the control group the treatment group but lower than that of model group (P<0.05);before the intervention, the model group and treatment group rats, the SOD level of GSH-PX was significantly lower than that of the control group (P<0.05);intervention treatment group SOD and GSH-PX Significantly lower than the blank group, but higher than the model group (P<0.05). Conclusion: Western medicine can significantly improve the islet function of T2DM model rats, reduce serum ceramide and chemerin levels, and improve the antioxidant function of rats.
文摘目的探讨甘精胰岛素U300联合口服降糖药治疗2型糖尿病的临床效果。方法选择2021年10月—2023年1月广东省吴川市人民医院收治的79例2型糖尿病患者,随机分为非甘精组(39例)和U300组(40例)。非甘精组口服降糖药物治疗,在此之上,U300组增加甘精胰岛素U300治疗,持续治疗3个月,对比2组血糖及相关指标变化,并监测患者胰岛素功能相关指标改善情况,评估低血糖反应等不良反应情况。结果治疗后,U300组血糖指标、血糖波动指标均显著低于非甘精组,差异有统计学意义(P<0.05)。U300组治疗后胰岛素功能指标均显著优于非甘精组,空腹及餐后2 h C肽均显著高于非甘精组,差异有统计学意义(P<0.05)。U300组低血糖反应发生率(2.50%,1/40)和不良反应总发生率(20.00%,8/40)与非甘精组(2.56,1/39;17.95%,7/39)比较,差异无统计学意义(P>0.05)。结论增加甘精胰岛素U300治疗,可更好地提升患者血糖管理效果,并可改善胰岛功能,有利于稳定控制血糖,有助于提高患者病情控制效果,应用效果安全可靠。
文摘目的探讨2型糖尿病湿热困脾证合并血脂紊乱患者胰岛功能变化及其影响因素。方法选择2020年1月—2020年12月医院收治的2型糖尿病湿热困脾证患者100例,根据美国ATPIII评估标准将其分为血脂紊乱组62例与血脂正常组38例。比较各组SF-36积分、胰岛素分泌功能(Homeostasis model assessment-β,HOMA-β)、胰岛素抵抗水平(Homeostasis model assessment-IR,HOMA-IR)、胰岛素敏感指数(Insulin sensitivity index,ISI)、空腹C肽和空腹胰岛素。应用单因素和多因素分析法研究血脂异常的相关因素。结果高甘油三酯组与混合型高脂组空腹胰岛素水平显著高于高胆固醇组与血脂正常组,差异有统计学意义(P<0.05)。高甘油三酯组空腹C肽水平显著高于高胆固醇组,差异有统计学意义(P<0.05)。混合型高脂组与高甘油三酯组的ISI水平低于高胆固醇组(P<0.05)。高甘油三酯组HOMA-β水平明显高于高胆固醇组与血脂正常组,差异有统计学意义(P<0.05)。高甘油三酯组及混合型高脂组HOMA-IR水平显著高于高胆固醇组,差异有统计学意义(P<0.05)。两组患者在躯体疼痛、整体健康、活力、社会功能和精神健康维度方面比较,差异有统计学意义(P<0.01)。多因素Logistic分析显示,喜食油腻、吸烟史、腰围和空腹胰岛素是2型糖尿病湿热困脾证患者血脂异常的危险因素,有氧运动是2型糖尿病湿热困脾证患者血脂异常的保护因素(P<0.05)。结论不同血脂紊乱类型对胰岛功能的影响并不相同,应针对相关因素积极预防,降低胰岛分泌负担,促使胰岛功能恢复。
