The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bio...The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.展开更多
上世纪50年代,减肥手术开始用于治疗肥胖症,最初的临床观察发现,肥胖患者术后不仅体重显著下降,而且其并发的非胰岛素依赖型糖尿病得到意想不到的治愈或改善。但这一现象并未引起关注,至1998年,East Carolina大学Brody医学院的Pories等...上世纪50年代,减肥手术开始用于治疗肥胖症,最初的临床观察发现,肥胖患者术后不仅体重显著下降,而且其并发的非胰岛素依赖型糖尿病得到意想不到的治愈或改善。但这一现象并未引起关注,至1998年,East Carolina大学Brody医学院的Pories等在Annals of Surgery杂志报道了减肥手术后的随访研究结果,才引起了学术界的高度重视。展开更多
An efficient stereoselective synthesis of the rigid aza-bicyclo[3.2.0]heptane scaffold has been developed to provide 2-cyano-pyrrolidine alpha-amino amide 1 as DPP-4 inhibitor.
SGLT-2 inhibitors(SGLT-2Is)have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases,heart failure,and diabetic kidney disease.Similarly,GLP-1 receptor agonists(...SGLT-2 inhibitors(SGLT-2Is)have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases,heart failure,and diabetic kidney disease.Similarly,GLP-1 receptor agonists(GLP-1RAs)have significantly improved atherosclerotic cardiovascular outcomes.To this end,DPP-4 inhibitors(DPP-4Is)are cardiac-neutral drugs.While long-acting GLP-1RAs have shown a favorable HbA1c lowering compared to DPP-4Is,there is no clinically meaningful HbA1c lowering difference between SGLT-2Is vs DPP-4Is.Moreover,the glucose-lowering potential of SGLT-2Is gets compromised with a progressive decline in renal functions,unlike DPP-4Is.Furthermore,the HbA1c lowering potential of DPP-4Is is favorable in people with T2DM having a modest baseline HbA1c(8.0%-8.5%)compared with SGLT-2Is which lowers HbA1c larger in a background of higher baseline HbA1c(>8.5%-9.0%).These findings suggest that the role of DPP-4Is in the management of type 2 diabetes mellitus cannot be completely ignored even in the era of SGLT-2Is.展开更多
Objective: To investigate the effects of DPP-4 inhibitor combined with metformin on blood glucose control, oxidative stress and inflammatory response in patients with type 2 diabetes mellitus (T2DM). Methods: A total ...Objective: To investigate the effects of DPP-4 inhibitor combined with metformin on blood glucose control, oxidative stress and inflammatory response in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 138 patients with newly diagnosed T2DM who were treated in the hospital between March 2016 and April 2017 were divided into routine group (n=69) and combined treatment group (n=69) by random number table method. Routine group were treated with metformin alone and combined treatment group received DPP-4 inhibitor combined with metformin therapy. The differences in blood glucose control as well as oxidative stress-related indicator and inflammatory factor contents were compared between the two groups before and after treatment. Results: Before treatment, the differences in blood glucose index levels in peripheral blood as well as the oxidative stress index and inflammatory mediator contents in serum were not statistically significant between the two groups. After 4 weeks of treatment, blood glucose indexes FBG and HOMA-IR levels in peripheral blood of combined treatment group were lower than those of routine group;oxidative stress indexes MDA and LHP contents in serum were lower than those of routine group whereas GSH-Px and T-AOC contents were higher than those of routine group;inflammatory mediators hs-CRP, IL-1 and IL-6 contents in serum were lower than those of routine group. Conclusion: DPP-4 inhibitor combined with metformin therapy can effectively control the blood glucose and suppress the systemic oxidative stress and inflammatory response in T2DM paients.展开更多
Objective: To study the effect of DPP-4 inhibitor combined with metformin on glucose and lipid metabolism and micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome. Metho...Objective: To study the effect of DPP-4 inhibitor combined with metformin on glucose and lipid metabolism and micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome. Methods: A total of 60 patients with type 2 diabetes mellitus complicated by metabolic syndrome who were treated in the hospital between February 2015 and December 2016 were divided into control group (n=30) and observation group (n=30) according to the random number table method. Control group received metformin therapy alone, observation group received DPP-4 inhibitor combined with metformin therapy, and the differences in levels of glucose and lipid metabolism indexes and inflammatory factors were compared between the two groups of patients before and after treatment. Results: Before treatment, the differences in glucose and lipid metabolism index levels in peripheral blood as well as inflammatory factor contents in serum were not statistically significant between the two groups. After treatment, the levels of glucose metabolism indexes FPG, FPI and HOMA-IR as well as lipid metabolism indexes TG and TC in peripheral blood of observation group were lower than those of control group while HDL-C level was higher than that of control group;the contents of inflammatory factors IL-6, CRP and TNF-α in serum were lower than those of control group. Conclusion: DPP-4 inhibitor combined with metformin therapy is more effective in controlling the glucose and lipid metabolism process and inhibiting the micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome.展开更多
AIM: The purpose of this research was to determine the changes of the inflammatory parameters in the long term with the use of dipeptidyl peptidase-4 inhibitors. Material and Methods: In this research we have retrospe...AIM: The purpose of this research was to determine the changes of the inflammatory parameters in the long term with the use of dipeptidyl peptidase-4 inhibitors. Material and Methods: In this research we have retrospectively reviewed the records of 80 patients who had added dipeptidyl peptidase-4 inhibitors (40 sitagliptin and 40 vildagliptin) to their ongoing therapies. Patients’ values of inflammation at the beginning of this process were taken as initial values, while values at the end of this process were considered as final values. Results: A total of 80 patients [38.8% (n = 31) of the patients were male, while 61.3% (n = 49) were female] enrolled in the study. When the whole group was evaluated, the mean age was 56.1 ± 9.7 years. The median follow-up time of the patients with DPP-4 inhibitors was 18 (2 - 64) months. The mean MPV value was measured as 8.79 ± 1.71 fL before DPP-4 inhibitors and it was 10.06 ± 1.42 fL after the follow-up period (p < 0.001). The median value serum GGT was 30.5 (13 - 194) U/L before DPP-4 inhibitor and 29.5 (12 - 112) U/L at the end (p = 0.048). The mean uric acid level before the use of di-peptidyl peptidase-4 inhibitors was 4.7 ± 1.6 mg/dL, and this level was 5.0 ± 1.5 mg/dL after the follow-up period (p = 0.048). Conclusion: In this study, it was observed that MPV and GGT levels were improved by dipeptidyl peptidase-4 inhibitors in long-term.展开更多
Objective: To investigate the effect of metformin combined with DPP-4 inhibitor on the micro-inflammatory status and insulin sensitivity of T2DM patients with metabolic syndrome. Methods: A total of 78 T2DM patients w...Objective: To investigate the effect of metformin combined with DPP-4 inhibitor on the micro-inflammatory status and insulin sensitivity of T2DM patients with metabolic syndrome. Methods: A total of 78 T2DM patients with metabolic syndrome who were treated in the hospital were retrospectively analyzed and divided into the control group (n=41) who received metformin therapy and the combined group (n=37) who received metformin combined with DPP-4 inhibitor therapy, and both groups were treated for 12 weeks. The differences in micro-inflammatory state and insulin sensitivity were compared between the two groups before and after treatment. Results: There was no statistically significant difference in serum inflammatory factor contents and peripheral blood insulin sensitivity-related index levels between the two groups before treatment. After 12 weeks of treatment, serum inflammatory factors IL-1, hs-CRP and TNF-α contents of combined group were lower than those of control group;insulin sensitivity indexes FGP, FINS, ISI and HOMA-IR levels were lower than those of control group. Conclusion: metformin combined with DPP-4 inhibitor Sitagliptin can more effectively inhibit the micro-inflammatory state and improve the insulin sensitivity in T2DM patients with metabolic syndrome.展开更多
文摘The objective of this study was to isolate and identify the intracellular bioactive peptides from mouse lymphocytes before and after lipopolysaccharide(LPS)stimulation,to explore novel peptides and to research the bioactive function.Mouse spleen lymphocytes were isolated and cultured with LPS stimulation(experimental group)or not(control group)to collect intracellular peptides.Totally 385 peptides were analyzed by nanoliter liquid phase-Q Exactive quadrupole ultra-high resolution orbitrap mass spectrometer(Nano LC-Q Exactive Plus)and identifi ed by PEAKS X software.After compared with peptides reported,131 novel peptides were discovered,which then were predicted bioactivity by Peptide Ranker and 6 peptides with high bioactivity were predicted function by BIOPEP-UMW database.Prediction data showed that they may have dipeptidyl peptidase IV(DPP-IV)inhibitory activity.Finally,two peptides showed better potent inhibition were verifi ed with competitive and noncompetitive modes.
文摘上世纪50年代,减肥手术开始用于治疗肥胖症,最初的临床观察发现,肥胖患者术后不仅体重显著下降,而且其并发的非胰岛素依赖型糖尿病得到意想不到的治愈或改善。但这一现象并未引起关注,至1998年,East Carolina大学Brody医学院的Pories等在Annals of Surgery杂志报道了减肥手术后的随访研究结果,才引起了学术界的高度重视。
文摘An efficient stereoselective synthesis of the rigid aza-bicyclo[3.2.0]heptane scaffold has been developed to provide 2-cyano-pyrrolidine alpha-amino amide 1 as DPP-4 inhibitor.
文摘SGLT-2 inhibitors(SGLT-2Is)have significantly improved cardio-renal outcomes and are preferred agents in people with cardiovascular diseases,heart failure,and diabetic kidney disease.Similarly,GLP-1 receptor agonists(GLP-1RAs)have significantly improved atherosclerotic cardiovascular outcomes.To this end,DPP-4 inhibitors(DPP-4Is)are cardiac-neutral drugs.While long-acting GLP-1RAs have shown a favorable HbA1c lowering compared to DPP-4Is,there is no clinically meaningful HbA1c lowering difference between SGLT-2Is vs DPP-4Is.Moreover,the glucose-lowering potential of SGLT-2Is gets compromised with a progressive decline in renal functions,unlike DPP-4Is.Furthermore,the HbA1c lowering potential of DPP-4Is is favorable in people with T2DM having a modest baseline HbA1c(8.0%-8.5%)compared with SGLT-2Is which lowers HbA1c larger in a background of higher baseline HbA1c(>8.5%-9.0%).These findings suggest that the role of DPP-4Is in the management of type 2 diabetes mellitus cannot be completely ignored even in the era of SGLT-2Is.
文摘Objective: To investigate the effects of DPP-4 inhibitor combined with metformin on blood glucose control, oxidative stress and inflammatory response in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 138 patients with newly diagnosed T2DM who were treated in the hospital between March 2016 and April 2017 were divided into routine group (n=69) and combined treatment group (n=69) by random number table method. Routine group were treated with metformin alone and combined treatment group received DPP-4 inhibitor combined with metformin therapy. The differences in blood glucose control as well as oxidative stress-related indicator and inflammatory factor contents were compared between the two groups before and after treatment. Results: Before treatment, the differences in blood glucose index levels in peripheral blood as well as the oxidative stress index and inflammatory mediator contents in serum were not statistically significant between the two groups. After 4 weeks of treatment, blood glucose indexes FBG and HOMA-IR levels in peripheral blood of combined treatment group were lower than those of routine group;oxidative stress indexes MDA and LHP contents in serum were lower than those of routine group whereas GSH-Px and T-AOC contents were higher than those of routine group;inflammatory mediators hs-CRP, IL-1 and IL-6 contents in serum were lower than those of routine group. Conclusion: DPP-4 inhibitor combined with metformin therapy can effectively control the blood glucose and suppress the systemic oxidative stress and inflammatory response in T2DM paients.
文摘Objective: To study the effect of DPP-4 inhibitor combined with metformin on glucose and lipid metabolism and micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome. Methods: A total of 60 patients with type 2 diabetes mellitus complicated by metabolic syndrome who were treated in the hospital between February 2015 and December 2016 were divided into control group (n=30) and observation group (n=30) according to the random number table method. Control group received metformin therapy alone, observation group received DPP-4 inhibitor combined with metformin therapy, and the differences in levels of glucose and lipid metabolism indexes and inflammatory factors were compared between the two groups of patients before and after treatment. Results: Before treatment, the differences in glucose and lipid metabolism index levels in peripheral blood as well as inflammatory factor contents in serum were not statistically significant between the two groups. After treatment, the levels of glucose metabolism indexes FPG, FPI and HOMA-IR as well as lipid metabolism indexes TG and TC in peripheral blood of observation group were lower than those of control group while HDL-C level was higher than that of control group;the contents of inflammatory factors IL-6, CRP and TNF-α in serum were lower than those of control group. Conclusion: DPP-4 inhibitor combined with metformin therapy is more effective in controlling the glucose and lipid metabolism process and inhibiting the micro-inflammatory state in patients with type 2 diabetes mellitus complicated by metabolic syndrome.
文摘AIM: The purpose of this research was to determine the changes of the inflammatory parameters in the long term with the use of dipeptidyl peptidase-4 inhibitors. Material and Methods: In this research we have retrospectively reviewed the records of 80 patients who had added dipeptidyl peptidase-4 inhibitors (40 sitagliptin and 40 vildagliptin) to their ongoing therapies. Patients’ values of inflammation at the beginning of this process were taken as initial values, while values at the end of this process were considered as final values. Results: A total of 80 patients [38.8% (n = 31) of the patients were male, while 61.3% (n = 49) were female] enrolled in the study. When the whole group was evaluated, the mean age was 56.1 ± 9.7 years. The median follow-up time of the patients with DPP-4 inhibitors was 18 (2 - 64) months. The mean MPV value was measured as 8.79 ± 1.71 fL before DPP-4 inhibitors and it was 10.06 ± 1.42 fL after the follow-up period (p < 0.001). The median value serum GGT was 30.5 (13 - 194) U/L before DPP-4 inhibitor and 29.5 (12 - 112) U/L at the end (p = 0.048). The mean uric acid level before the use of di-peptidyl peptidase-4 inhibitors was 4.7 ± 1.6 mg/dL, and this level was 5.0 ± 1.5 mg/dL after the follow-up period (p = 0.048). Conclusion: In this study, it was observed that MPV and GGT levels were improved by dipeptidyl peptidase-4 inhibitors in long-term.
文摘Objective: To investigate the effect of metformin combined with DPP-4 inhibitor on the micro-inflammatory status and insulin sensitivity of T2DM patients with metabolic syndrome. Methods: A total of 78 T2DM patients with metabolic syndrome who were treated in the hospital were retrospectively analyzed and divided into the control group (n=41) who received metformin therapy and the combined group (n=37) who received metformin combined with DPP-4 inhibitor therapy, and both groups were treated for 12 weeks. The differences in micro-inflammatory state and insulin sensitivity were compared between the two groups before and after treatment. Results: There was no statistically significant difference in serum inflammatory factor contents and peripheral blood insulin sensitivity-related index levels between the two groups before treatment. After 12 weeks of treatment, serum inflammatory factors IL-1, hs-CRP and TNF-α contents of combined group were lower than those of control group;insulin sensitivity indexes FGP, FINS, ISI and HOMA-IR levels were lower than those of control group. Conclusion: metformin combined with DPP-4 inhibitor Sitagliptin can more effectively inhibit the micro-inflammatory state and improve the insulin sensitivity in T2DM patients with metabolic syndrome.
