BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hyp...BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment.AIM To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy.METHODS At 24 wk,343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis.On the basis of the reduction in the WHtR,these participants were divided into the following two groups:LowΔWHtR group and highΔWHtR group.Metabolic and related parameters associated with a highΔWHtR were investigated using univariate and multivariate logistic regression analyses.RESULTS A significant decrease in the WHtR was observed in both treatment groups(acarbose:-0.015,95%confidence interval[CI]:-0.018 to-0.012,P<0.001;metformin:-0.013,95%CI:-0.016 to-0.010,P<0.001).In both the acarbose and metformin groups,the WHtR of the women was more likely to be reduced than that of the men.In the acarbose group,a lower baseline area under the curve of glucagon-like peptide 1(AUCGLP-1)was associated with a highΔWHtR(odds ratio[OR]=0.796,P<0.001),while a higher baseline AUCGLP-1 was associated with a highΔWHtR in the patients treated with metformin(OR=1.133,P=0.025).Regarding the changes from baseline,an increase in AUCGLP-1 was associated with a highΔWHtR in the acarbose(OR=1.121,P=0.016)but not metformin group.A higher reduction in high-density lipoprotein cholesterol/non-highdensity lipoprotein cholesterol was also associated with a highΔWHtR in the acarbose arm(OR=20.735,P=0.001).In the metformin arm,a higher reduction in fasting plasma glucose(OR=0.843,P=0.039)and total cholesterol was associated with a highΔWHtR(OR=0.743,P=0.013).CONCLUSION A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.展开更多
Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments ha...Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments have been preferred over the last 10 to 15 years,the use of acarbose is not as common in treating type 2 diabetes as before.Some studies have shown that acarbose also produces a weight-loss effect by increasing glucagon-like peptide 1(GLP-1).The positive effect of acarbose on GLP-1,and increasing evidence that it provides cardiovascular protection,suggests that acarbose may again be considered among the first-choice antidiabetic agents,as it was in the 1990s.展开更多
Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the num...Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the number parity of entry sequence, 100 cases of elder patients with early-onset type 2 Diabetes Mellitus are divided into the control group and the observation group of 50 cases. The control group was treated with novolin and acarbose, the observation group was given subcutaneous injection of levemir and acarbose treatment. Compare the T cell subsets and function of isletβ cells in two group of patients before the treatment (T0), treatment for 4 weeks (T1) ,treatment for 8 weeks (T2).Results:(1) The levels of T0, T1, T2CD3+, CD4+, CD4+/CD8+ were increased in both groups, and CD8+ decreased. Among them, the levels of T1, T2CD3+, CD4+, CD4+/CD8+ of the observation group were obviously higher than the control group, the level of CD8+ was lowly than the control group, the difference was statistically significant;(2) In the stage of T0, T1, T2, the levels of FPG, HbA1c, HOMA-IR were showed a downward trend, the levels of FIns, HOMA-B were increased. In these two groups, the levels of T1, T2FPG, HbA1c, HOMA-IR of the observation group were lower than the control group, and the levels of FIns, HOMA-B were higher than the control group, the difference was statistically significant;(3) In the control group occurred 3 cases of hypoglycemia, and the incidence of adverse reactions was 6%. However, in the observation group no occurred adverse reactions, the difference was statistically significant.Conclusions:The combined therapy of levemir and acarbose in elder patients with early-onset type 2 Diabetes Mellitus, It helps to improve immune function, protect the isletβ-cell function.展开更多
Objectives: To investigate the effects of insulin resistance on serum androgen level and ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic role of acarbose in the treatment of hyperinsulinemi...Objectives: To investigate the effects of insulin resistance on serum androgen level and ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic role of acarbose in the treatment of hyperinsulinemia, postprandial hyperglycemia and anovulation. Methods: 14 women accompanied by postprandial hyperglycemia with PCOS were administrated by acarbose for 12 weeks.14 age-matched individuals who had similar body mass index and normal menstruation were served as controls. Results: Serum T levels declined significantly from 4.09±1.04 nmol/L to 1.71±0.54 nmol/L (P<0.001), after acarbose treatment for 12 weeks. 12 out of 14 cases restored ovulation and menstrual cycles after acarbose treatment, among which 4 got pregnant. Conclusion: Acarbose may play a role on reducing postprandial hyperglycemia and HbAic levels, increase ISI and FSG/FI, indirectly reduce serum androgen levels through reducing plasma insulin level and recover ovarian ovulation in PCOS women with postprandial hyperglycemia.展开更多
Theα-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp.and used as a potent drug in the treatment of type-2 diabetes.In order to improve the yield of acarbose,an efficient genetic manipulatio...Theα-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp.and used as a potent drug in the treatment of type-2 diabetes.In order to improve the yield of acarbose,an efficient genetic manipulation system for Actinoplanes sp.was established.The conjugation system between E.coli carryingØC31-derived integrative plasmids and the mycelia of Actinoplanes sp.SE50/110 was optimized by adjusting the parameters of incubation time of mixed culture(mycelia and E.coli),quantity of recipient cells,donor-to-recipient ratio and the concentration of MgCl2,which resulted in a high conjugation efficiency of 29.4%.Using this integrative system,a cloned acarbose biosynthetic gene cluster was introduced into SE50/110,resulting in a 35%increase of acarbose titer from 2.35 to 3.18 g/L.Alternatively,a pIJ101-derived replicating plasmid combined with the counter-selection system CodA(sm)was constructed for gene inactivation,which has a conjugation frequency as high as 0.52%.Meanwhile,almost all 5-flucytosine-resistant colonies were sensitive to apramycin,among which 75%harbored the successful deletion of targeted genes.Using this replicating vector,the maltooligosyltrehalose synthase gene treY responsible for the accumulation of component C was inactivated,and component C was eliminated as detected by LC-MS.Based on an efficient genetic manipulation system,improved acarbose production and the elimination of component C in our work paved a way for future rational engineering of the acarbose-producing strains.展开更多
Theα-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp.SE50 and used widely for the treatment of type-2 diabetes.Compared with the wild-type SE50,a high-yield derivativ...Theα-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp.SE50 and used widely for the treatment of type-2 diabetes.Compared with the wild-type SE50,a high-yield derivative Actinoplanes sp.SE50/110 shows 2-fold and 3–7-fold improvement of acarbose yield and acb cluster transcription,respectively.The genome of SE50 was fully sequenced and compared with that of SE50/110,and 11 SNVs and 4 InDels,affecting 8 CDSs,were identified in SE50/110.The 8 CDSs were individually inactivated in SE50.Deletions of ACWT_4325(encoding alcohol dehydrogenase)resulted in increases of acarbose yield by 25%from 1.87 to 2.34 g/L,acetyl-CoA concentration by 52.7%,and PEP concentration by 22.7%.Meanwhile,deletion of ACWT_7629(encoding elongation factor G)caused improvements of acarbose yield by 36%from 1.87 to 2.54 g/L,transcription of acb cluster,and ppGpp concentration to 2.2 folds.Combined deletions of ACWT_4325 and ACWT_7629 resulted in further improvement of acarbose to 2.83 g/L(i.e.76%of SE50/110),suggesting that the metabolic perturbation and improved transcription of acb cluster caused by these two mutations contribute substantially to the acarbose overproduction.Enforced application of similar strategies was performed to manipulate SE50/110,resulting in a further increase of acarbose titer from 3.73 to 4.21 g/L.Therefore,the comparative genomics approach combined with functional verification not only revealed the acarbose overproduction mechanisms,but also guided further engineering of its high-yield producers.展开更多
Objective To evaluate the effects of Acarbose on incretin level(glucagon-like peptide 1(GLP-1)and gastric inhibitory polypeptide(GIP)of type 2 diabetes mellitus(T2DM)patients after different kinds of glucose load.Meth...Objective To evaluate the effects of Acarbose on incretin level(glucagon-like peptide 1(GLP-1)and gastric inhibitory polypeptide(GIP)of type 2 diabetes mellitus(T2DM)patients after different kinds of glucose load.Methods A total of 32 newly diagnosed T2DM patients were enrolled in this study and randomly divided into展开更多
Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from ...Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.展开更多
BACKGROUND Previous studies have shown that diabetes mellitus is a common comorbidity of coronavirus disease 2019(COVID-19),but the effects of diabetes or anti-diabetic medication on the mortality of COVID-19 have not...BACKGROUND Previous studies have shown that diabetes mellitus is a common comorbidity of coronavirus disease 2019(COVID-19),but the effects of diabetes or anti-diabetic medication on the mortality of COVID-19 have not been well described.AIM To investigate the outcome of different statuses(with or without comorbidity)and anti-diabetic medication use before admission of diabetic after COVID-19.METHODS In this multicenter and retrospective study,we enrolled 1422 consecutive hospitalized patients from January 21,2020,to March 25,2020,at six hospitals in Hubei Province,China.The primary endpoint was in-hospital mortality.Epidemiological material,demographic information,clinical data,laboratory parameters,radiographic characteristics,treatment and outcome were extracted from electronic medical records using a standardized data collection form.Most of the laboratory data except fasting plasma glucose(FPG)were obtained in first hospitalization,and FPG was collected in the next day morning.Major clinical symptoms,vital signs at admission and comorbidities were collected.The treatment data included not only COVID-19 but also diabetes mellitus.The duration from the onset of symptoms to admission,illness severity,intensive care unit(ICU)admission,and length of hospital stay were also recorded.All data were checked by a team of sophisticated physicians.RESULTS Patients with diabetes were 10 years older than non-diabetic patients[(39-64)vs(56-70),P<0.001]and had a higher prevalence of comorbidities such as hypertension(55.5%vs 21.4%,P<0.001),coronary heart disease(CHD)(9.9%vs 3.5%,P<0.001),cerebrovascular disease(CVD)(3%vs 2.2%,P<0.001),and chronic kidney disease(CKD)(4.7%vs 1.5%,P=0.007).Mortality(13.6%vs 7.2%,P=0.003)was more prevalent among the diabetes group.Further analysis revealed that patients with diabetes who took acarbose had a lower mortality rate(2.2%vs 26.1,P<0.01).Multivariable Cox regression showed that male sex[hazard ratio(HR)2.59(1.68-3.99),P<0.001],hypertension[HR 1.75(1.18-2.60),P=0.006),CKD[HR 4.55(2.52-8.20),P<0.001],CVD[HR 2.35(1.27-4.33),P=0.006],and age were risk factors for the COVID-19 mortality.Higher HRs were noted in those aged≥65(HR 11.8[4.6-30.2],P<0.001)vs 50-64 years(HR 5.86[2.27-15.12],P<0.001).The survival curve revealed that,compared with the diabetes only group,the mortality was increased in the diabetes with comorbidities group(P=0.009)but was not significantly different from the noncomorbidity group(P=0.59).CONCLUSION Patients with diabetes had worse outcomes when suffering from COVID-19;however,the outcome was not associated with diabetes itself but with comorbidities.Furthermore,acarbose could reduce the mortality in diabetic.展开更多
Differences between the inhibitory activities of specific compounds on analogous enzymes isolated from different animal species are one of the critical issues to evaluate when exploring structure-activity relationship...Differences between the inhibitory activities of specific compounds on analogous enzymes isolated from different animal species are one of the critical issues to evaluate when exploring structure-activity relationships. The activity of acarbose is about ten times stronger in rat than in human, and that of neosalacinol is similar in both species. Binding affinities of acarbose and neosalacinol to four catalytic domains of alpha-glucosidases in human and rat were compared to investigate the cause of activity differences among species. Species difference was brought about complicatedly by the balance of interaction with four domains, and the result was indicated that larger ligand would show larger species difference in activity.展开更多
Human maltase-glucoamylase(MGAM)hydrolyzes linear alpha-1,4-linked oligosaccharide substrates,playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 di...Human maltase-glucoamylase(MGAM)hydrolyzes linear alpha-1,4-linked oligosaccharide substrates,playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity.The amino-and carboxyl-terminal portions of MGAM(MGAM-N and MGAM-C)carry out the same catalytic reaction but have different substrate specificities.In this study,we report crystal structures of MGAM-C alone at a resolution of 3.1Å,and in complex with its inhibitor acarbose at a resolution of 2.9Å.Structural studies,combined with biochemical analysis,revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites(+2 and+3 subsites),accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N.Moreover,we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides.These results provide important information for understanding the substrate specificity of alphaglucosidases during the process of terminal starch digestion,and for designing more efficient drugs to control type 2 diabetes or obesity.展开更多
基金This study is registered at Chinese Clinical Trial Registry Center.The registration number is ChiCTRTRC-08000231.
文摘BACKGROUND The waist-to-height ratio(WHtR)is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients.The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment.AIM To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy.METHODS At 24 wk,343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis.On the basis of the reduction in the WHtR,these participants were divided into the following two groups:LowΔWHtR group and highΔWHtR group.Metabolic and related parameters associated with a highΔWHtR were investigated using univariate and multivariate logistic regression analyses.RESULTS A significant decrease in the WHtR was observed in both treatment groups(acarbose:-0.015,95%confidence interval[CI]:-0.018 to-0.012,P<0.001;metformin:-0.013,95%CI:-0.016 to-0.010,P<0.001).In both the acarbose and metformin groups,the WHtR of the women was more likely to be reduced than that of the men.In the acarbose group,a lower baseline area under the curve of glucagon-like peptide 1(AUCGLP-1)was associated with a highΔWHtR(odds ratio[OR]=0.796,P<0.001),while a higher baseline AUCGLP-1 was associated with a highΔWHtR in the patients treated with metformin(OR=1.133,P=0.025).Regarding the changes from baseline,an increase in AUCGLP-1 was associated with a highΔWHtR in the acarbose(OR=1.121,P=0.016)but not metformin group.A higher reduction in high-density lipoprotein cholesterol/non-highdensity lipoprotein cholesterol was also associated with a highΔWHtR in the acarbose arm(OR=20.735,P=0.001).In the metformin arm,a higher reduction in fasting plasma glucose(OR=0.843,P=0.039)and total cholesterol was associated with a highΔWHtR(OR=0.743,P=0.013).CONCLUSION A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.
文摘Acarbose is an agent that has been used to treat type 2 diabetes for about 30 years;it prevents postprandial hyperglycemia by inhibiting carbohydrate digestion in the small intestine.Since incretin-based treatments have been preferred over the last 10 to 15 years,the use of acarbose is not as common in treating type 2 diabetes as before.Some studies have shown that acarbose also produces a weight-loss effect by increasing glucagon-like peptide 1(GLP-1).The positive effect of acarbose on GLP-1,and increasing evidence that it provides cardiovascular protection,suggests that acarbose may again be considered among the first-choice antidiabetic agents,as it was in the 1990s.
文摘Objective:To discuss the effect of the combined therapy of levemir and acarbose on T cell subsets and function of isletβ cells in elder patients with early-onset type 2 Diabetes Mellitus. Methods:According to the number parity of entry sequence, 100 cases of elder patients with early-onset type 2 Diabetes Mellitus are divided into the control group and the observation group of 50 cases. The control group was treated with novolin and acarbose, the observation group was given subcutaneous injection of levemir and acarbose treatment. Compare the T cell subsets and function of isletβ cells in two group of patients before the treatment (T0), treatment for 4 weeks (T1) ,treatment for 8 weeks (T2).Results:(1) The levels of T0, T1, T2CD3+, CD4+, CD4+/CD8+ were increased in both groups, and CD8+ decreased. Among them, the levels of T1, T2CD3+, CD4+, CD4+/CD8+ of the observation group were obviously higher than the control group, the level of CD8+ was lowly than the control group, the difference was statistically significant;(2) In the stage of T0, T1, T2, the levels of FPG, HbA1c, HOMA-IR were showed a downward trend, the levels of FIns, HOMA-B were increased. In these two groups, the levels of T1, T2FPG, HbA1c, HOMA-IR of the observation group were lower than the control group, and the levels of FIns, HOMA-B were higher than the control group, the difference was statistically significant;(3) In the control group occurred 3 cases of hypoglycemia, and the incidence of adverse reactions was 6%. However, in the observation group no occurred adverse reactions, the difference was statistically significant.Conclusions:The combined therapy of levemir and acarbose in elder patients with early-onset type 2 Diabetes Mellitus, It helps to improve immune function, protect the isletβ-cell function.
文摘Objectives: To investigate the effects of insulin resistance on serum androgen level and ovulation of women with polycystic ovary syndrome (PCOS) and observe clinic role of acarbose in the treatment of hyperinsulinemia, postprandial hyperglycemia and anovulation. Methods: 14 women accompanied by postprandial hyperglycemia with PCOS were administrated by acarbose for 12 weeks.14 age-matched individuals who had similar body mass index and normal menstruation were served as controls. Results: Serum T levels declined significantly from 4.09±1.04 nmol/L to 1.71±0.54 nmol/L (P<0.001), after acarbose treatment for 12 weeks. 12 out of 14 cases restored ovulation and menstrual cycles after acarbose treatment, among which 4 got pregnant. Conclusion: Acarbose may play a role on reducing postprandial hyperglycemia and HbAic levels, increase ISI and FSG/FI, indirectly reduce serum androgen levels through reducing plasma insulin level and recover ovarian ovulation in PCOS women with postprandial hyperglycemia.
基金We are grateful to Prof.Yuhui Sun from Wuhan university,China,and the late Prof.Keqian Yang from Institute of Microbiology,Chinese Academy of Sciences,for providing plasmids pWHU2653 and pDR-4-K^*,respectively.This work was supported by grants from the National Natural Science Foundation of China(No.31470157,21661140002)the Ministry of Science and Technology of China(No.2012AA02A706).
文摘Theα-glucosidase inhibitor acarbose is commercially produced by Actinoplanes sp.and used as a potent drug in the treatment of type-2 diabetes.In order to improve the yield of acarbose,an efficient genetic manipulation system for Actinoplanes sp.was established.The conjugation system between E.coli carryingØC31-derived integrative plasmids and the mycelia of Actinoplanes sp.SE50/110 was optimized by adjusting the parameters of incubation time of mixed culture(mycelia and E.coli),quantity of recipient cells,donor-to-recipient ratio and the concentration of MgCl2,which resulted in a high conjugation efficiency of 29.4%.Using this integrative system,a cloned acarbose biosynthetic gene cluster was introduced into SE50/110,resulting in a 35%increase of acarbose titer from 2.35 to 3.18 g/L.Alternatively,a pIJ101-derived replicating plasmid combined with the counter-selection system CodA(sm)was constructed for gene inactivation,which has a conjugation frequency as high as 0.52%.Meanwhile,almost all 5-flucytosine-resistant colonies were sensitive to apramycin,among which 75%harbored the successful deletion of targeted genes.Using this replicating vector,the maltooligosyltrehalose synthase gene treY responsible for the accumulation of component C was inactivated,and component C was eliminated as detected by LC-MS.Based on an efficient genetic manipulation system,improved acarbose production and the elimination of component C in our work paved a way for future rational engineering of the acarbose-producing strains.
基金the National Natural Science Foundation of China(No.31470157,21661140002,31830104,U1703236)the Shanghai Science and Technology Committee(No.17JC1403600)。
文摘Theα-glucosidase inhibitor acarbose is produced in large-scale by strains derived from Actinoplanes sp.SE50 and used widely for the treatment of type-2 diabetes.Compared with the wild-type SE50,a high-yield derivative Actinoplanes sp.SE50/110 shows 2-fold and 3–7-fold improvement of acarbose yield and acb cluster transcription,respectively.The genome of SE50 was fully sequenced and compared with that of SE50/110,and 11 SNVs and 4 InDels,affecting 8 CDSs,were identified in SE50/110.The 8 CDSs were individually inactivated in SE50.Deletions of ACWT_4325(encoding alcohol dehydrogenase)resulted in increases of acarbose yield by 25%from 1.87 to 2.34 g/L,acetyl-CoA concentration by 52.7%,and PEP concentration by 22.7%.Meanwhile,deletion of ACWT_7629(encoding elongation factor G)caused improvements of acarbose yield by 36%from 1.87 to 2.54 g/L,transcription of acb cluster,and ppGpp concentration to 2.2 folds.Combined deletions of ACWT_4325 and ACWT_7629 resulted in further improvement of acarbose to 2.83 g/L(i.e.76%of SE50/110),suggesting that the metabolic perturbation and improved transcription of acb cluster caused by these two mutations contribute substantially to the acarbose overproduction.Enforced application of similar strategies was performed to manipulate SE50/110,resulting in a further increase of acarbose titer from 3.73 to 4.21 g/L.Therefore,the comparative genomics approach combined with functional verification not only revealed the acarbose overproduction mechanisms,but also guided further engineering of its high-yield producers.
文摘Objective To evaluate the effects of Acarbose on incretin level(glucagon-like peptide 1(GLP-1)and gastric inhibitory polypeptide(GIP)of type 2 diabetes mellitus(T2DM)patients after different kinds of glucose load.Methods A total of 32 newly diagnosed T2DM patients were enrolled in this study and randomly divided into
文摘Non-alcoholic fatty liver disease (NAFLD) encompasses a histological spectrum ranging from simple steatosis to steatohepatitis,advanced fibrosis and inflammatory changes.Ezetimibe inhibits cholesterol absorption from the intestinal lumen into enterocytes.The molecular target of ezetimibe is the sterol transporter Niemann-Pick C1-like 1 protein (NPC1L1).Human NPC1L1 is abundantly expressed in the liver and may facilitate the hepatic accumulation of cholesterol.Ezetimibe ex-erts beneficial effects on several metabolic variables.Ezetimibe treatment attenuates hepatic steatosis and is beneficial in terms of NAFLD biochemical markers.The combination of ezetimibe with other interventions may also be beneficial in NAFLD patients.Our group inves-tigated the ezetimibe-orlistat combination treatment in overweight and obese patients with hypercholeste-rolemia,with beneficial effects on NAFLD biochemical markers.These results are promising for patients with NAFLD,who usually have increased cardiovascular disease risk and need a multifactorial treatment.How-ever,it should be mentioned that most results are from animal studies and,although modest elevation of liver function tests may raise the suspicion of NAFLD,none of these tests are sensitive to establish the diagnosis of NAFLD with great accuracy.
基金Supported by National Natural Science Foundation of China(General Program)No.81670815+1 种基金Guangdong Basic and Applied Basic Research Foundation,No.2020A1515010124,No.2021A1515010695Special Fund for Innovation Strategy of Science and Technology plan of Guangdong Province,No.2019A030317011。
文摘BACKGROUND Previous studies have shown that diabetes mellitus is a common comorbidity of coronavirus disease 2019(COVID-19),but the effects of diabetes or anti-diabetic medication on the mortality of COVID-19 have not been well described.AIM To investigate the outcome of different statuses(with or without comorbidity)and anti-diabetic medication use before admission of diabetic after COVID-19.METHODS In this multicenter and retrospective study,we enrolled 1422 consecutive hospitalized patients from January 21,2020,to March 25,2020,at six hospitals in Hubei Province,China.The primary endpoint was in-hospital mortality.Epidemiological material,demographic information,clinical data,laboratory parameters,radiographic characteristics,treatment and outcome were extracted from electronic medical records using a standardized data collection form.Most of the laboratory data except fasting plasma glucose(FPG)were obtained in first hospitalization,and FPG was collected in the next day morning.Major clinical symptoms,vital signs at admission and comorbidities were collected.The treatment data included not only COVID-19 but also diabetes mellitus.The duration from the onset of symptoms to admission,illness severity,intensive care unit(ICU)admission,and length of hospital stay were also recorded.All data were checked by a team of sophisticated physicians.RESULTS Patients with diabetes were 10 years older than non-diabetic patients[(39-64)vs(56-70),P<0.001]and had a higher prevalence of comorbidities such as hypertension(55.5%vs 21.4%,P<0.001),coronary heart disease(CHD)(9.9%vs 3.5%,P<0.001),cerebrovascular disease(CVD)(3%vs 2.2%,P<0.001),and chronic kidney disease(CKD)(4.7%vs 1.5%,P=0.007).Mortality(13.6%vs 7.2%,P=0.003)was more prevalent among the diabetes group.Further analysis revealed that patients with diabetes who took acarbose had a lower mortality rate(2.2%vs 26.1,P<0.01).Multivariable Cox regression showed that male sex[hazard ratio(HR)2.59(1.68-3.99),P<0.001],hypertension[HR 1.75(1.18-2.60),P=0.006),CKD[HR 4.55(2.52-8.20),P<0.001],CVD[HR 2.35(1.27-4.33),P=0.006],and age were risk factors for the COVID-19 mortality.Higher HRs were noted in those aged≥65(HR 11.8[4.6-30.2],P<0.001)vs 50-64 years(HR 5.86[2.27-15.12],P<0.001).The survival curve revealed that,compared with the diabetes only group,the mortality was increased in the diabetes with comorbidities group(P=0.009)but was not significantly different from the noncomorbidity group(P=0.59).CONCLUSION Patients with diabetes had worse outcomes when suffering from COVID-19;however,the outcome was not associated with diabetes itself but with comorbidities.Furthermore,acarbose could reduce the mortality in diabetic.
文摘Differences between the inhibitory activities of specific compounds on analogous enzymes isolated from different animal species are one of the critical issues to evaluate when exploring structure-activity relationships. The activity of acarbose is about ten times stronger in rat than in human, and that of neosalacinol is similar in both species. Binding affinities of acarbose and neosalacinol to four catalytic domains of alpha-glucosidases in human and rat were compared to investigate the cause of activity differences among species. Species difference was brought about complicatedly by the balance of interaction with four domains, and the result was indicated that larger ligand would show larger species difference in activity.
基金by the National Basic Research Program of China(973 Program)(Grant Nos.2007CB914301 and 2007CB 914803)the Natural Science Foundation of China(Grant Nos.30940015,30770428,21002052 and 31170684)the TBR Program(No.08QTPTJC 28200,08SYSYTC00200 and 10JCYB JC14300).
文摘Human maltase-glucoamylase(MGAM)hydrolyzes linear alpha-1,4-linked oligosaccharide substrates,playing a crucial role in the production of glucose in the human lumen and acting as an efficient drug target for type 2 diabetes and obesity.The amino-and carboxyl-terminal portions of MGAM(MGAM-N and MGAM-C)carry out the same catalytic reaction but have different substrate specificities.In this study,we report crystal structures of MGAM-C alone at a resolution of 3.1Å,and in complex with its inhibitor acarbose at a resolution of 2.9Å.Structural studies,combined with biochemical analysis,revealed that a segment of 21 amino acids in the active site of MGAM-C forms additional sugar subsites(+2 and+3 subsites),accounting for the preference for longer substrates of MAGM-C compared with that of MGAM-N.Moreover,we discovered that a single mutation of Trp1251 to tyrosine in MGAM-C imparts a novel catalytic ability to digest branched alpha-1,6-linked oligosaccharides.These results provide important information for understanding the substrate specificity of alphaglucosidases during the process of terminal starch digestion,and for designing more efficient drugs to control type 2 diabetes or obesity.
