Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recen...Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate(MSG)-induced obese mice,suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance(IGT) to T2 DM. In this study, we evaluated the effect of JTN on the progression of T2 DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment,blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp.Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones(insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase(GCK), pyruvate carboxylase(PCB) and pancreas duodenum homeobox-1(PDX-1), while down-regulating C/EBP homologous protein(Chop)expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum(ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2 DM.展开更多
Objective:To assess the efficacy and safety of mulberry twig alkaloids(Sangzhi alkaloids,SZ-A)for treatment of type 2 diabetes in a randomized,double-blind,placebo-controlled multicenter clinical trial.Methods:A total...Objective:To assess the efficacy and safety of mulberry twig alkaloids(Sangzhi alkaloids,SZ-A)for treatment of type 2 diabetes in a randomized,double-blind,placebo-controlled multicenter clinical trial.Methods:A total of 200 patients were randomized to receive SZ-A(n=100)or placebo(n=100)for 16 weeks.The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs.The primary outcome was the change in glycosylated hemoglobin(Hb A1c)level.The secondary outcome included the proportions of cases with Hb A1c<7.0%and Hb A1c<6.5%,fasting blood glucose(FBG),postprandial blood glucose(PBG),area under curve for the PBG(AUC_(0-2h)),body weight,and body mass index(BMI).Adverse events(AEs),severe adverse events(SAEs),treatment-related adverse events(TAEs),gastrointestinal disorders(GDs),blood pressure,routine blood tests,and liver and kidney function were monitored.Results:Compared with baseline,the change of Hb A1c at week 16 was-0.80%(95%CI:-0.98%to-0.62%)and-0.09%(95%CI:-0.27%to 0.09%)in SZ-A group and placebo group,respectively.The proportion of patients with Hb A1c<7%and<6.5%was higher in the SZ-A group than in the placebo group(46.8%vs.21.6%and 29.9%vs.10.8%).The observed values and changes in FBG,1 h-PBG,2 h-PBG,and AUC_(0-2h) differed significantly between groups(P<0.001),but differences were not significant in body weight and BMI(P>0.05).The incidence rates of AEs,TAEs,and GDs differed significantly between groups(P=0.010,P=0.005,and P=0.006,respectively),whereas the incidence rates of SAEs showed no significant differences between groups(P=1.000).Conclusion:SZ-A are effective and safe for treatment of type 2 diabetes.展开更多
基金supported by the Drug Innovation Major Project in China (Nos. 2018ZX09711001-003-011 and 2018ZX09711-001-009-014)the National Natural Science Foundation of China (No. 81973379)the Natural Science Foundation of Beijing Municipality (No. 7202137)。
文摘Jin-tang-ning(JTN), a Chinese patent medicine, mainly comprised of Bombyx mori L., has been proved to show α-glucosidase inhibitory efficacy and clinically effective for the treatment of type 2 diabetes(T2 DM). Recently, we have reported that JTN could ameliorate postprandial hyperglycemia and improved β cell function in monosodium glutamate(MSG)-induced obese mice,suggesting that JTN might play a potential role in preventing the conversion of impaired glucose tolerance(IGT) to T2 DM. In this study, we evaluated the effect of JTN on the progression of T2 DM in the pre-diabetic KKAy mice. During the 10 weeks of treatment,blood biochemical analysis and oral glucose tolerance tests were performed to evaluate glucose and lipid profiles. The β cell function was quantified using hyperglycemic clamp at the end of the study. JTN-treated groups exhibited slowly raised fasting and postprandial blood glucose levels, and also ameliorated lipid profile. JTN improved glucose intolerance after 8 weeks of treatment. Meanwhile, JTN restored glucose-stimulated first-phase of insulin secretion and induced higher maximum insulin levels in the hyperglycemic clamp.Thus, to investigate the underlying mechanisms of JTN in protecting β cell function, the morphologic changes of the pancreatic islets were observed by optical microscope and immunofluorescence of hormones(insulin and glucagon). Pancreatic protein expression levels of key factors involving in insulin secretion-related pathway and ER stress were also detected by Western blot. Pre-diabetic KKAy mice exhibited a compensatory augment in β cell mass and abnormal α cell distribution. Long-term treatment of JTN recovered islet morphology accompanied by reducing α cell area in KKAy mice. JTN upregulated expression levels of glucokinase(GCK), pyruvate carboxylase(PCB) and pancreas duodenum homeobox-1(PDX-1), while down-regulating C/EBP homologous protein(Chop)expression in pancreas of the hyperglycemic clamp, which indicated the improvement of mitochondrial metabolism and relief of endoplasmic reticulum(ER) stress of β cells after JTN treatment. These results will provide a new insight into exploring a novel strategy of JTN for protecting β cell function and preventing the onset of pre-diabetes to T2 DM.
基金Supported by the National Major Science and Technology Projects of China(No.2013ZX09101005)。
文摘Objective:To assess the efficacy and safety of mulberry twig alkaloids(Sangzhi alkaloids,SZ-A)for treatment of type 2 diabetes in a randomized,double-blind,placebo-controlled multicenter clinical trial.Methods:A total of 200 patients were randomized to receive SZ-A(n=100)or placebo(n=100)for 16 weeks.The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs.The primary outcome was the change in glycosylated hemoglobin(Hb A1c)level.The secondary outcome included the proportions of cases with Hb A1c<7.0%and Hb A1c<6.5%,fasting blood glucose(FBG),postprandial blood glucose(PBG),area under curve for the PBG(AUC_(0-2h)),body weight,and body mass index(BMI).Adverse events(AEs),severe adverse events(SAEs),treatment-related adverse events(TAEs),gastrointestinal disorders(GDs),blood pressure,routine blood tests,and liver and kidney function were monitored.Results:Compared with baseline,the change of Hb A1c at week 16 was-0.80%(95%CI:-0.98%to-0.62%)and-0.09%(95%CI:-0.27%to 0.09%)in SZ-A group and placebo group,respectively.The proportion of patients with Hb A1c<7%and<6.5%was higher in the SZ-A group than in the placebo group(46.8%vs.21.6%and 29.9%vs.10.8%).The observed values and changes in FBG,1 h-PBG,2 h-PBG,and AUC_(0-2h) differed significantly between groups(P<0.001),but differences were not significant in body weight and BMI(P>0.05).The incidence rates of AEs,TAEs,and GDs differed significantly between groups(P=0.010,P=0.005,and P=0.006,respectively),whereas the incidence rates of SAEs showed no significant differences between groups(P=1.000).Conclusion:SZ-A are effective and safe for treatment of type 2 diabetes.
