The Chinese patent medicine, Jin-tang-ning, ameliorates hyperglycemia through improving β cell function in pre-diabetic KKAy mice  

作　　者：LIU Shuai-Nan LIU Quan LEI Lei SUN Su-Juan LI Cai-Na HUAN Yi HOU Shao-Cong SHEN Zhu-Fang 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Key laboratory of Polymorphic Drugs of Bejing,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Bejing 100050,China

出　　处：《Chinese Journal of Natural Medicines》2020年第11期827-836,共10页中国天然药物（英文版）

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)。

摘　　要：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 relie

关 键 词：Jin-tang-ning(JTN) PRE-DIABETES βCell function Type 2 diabetes ER stress 

分 类 号：R965[医药卫生—药理学]