Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus

作     者：Vishal J Patel Amit A Joharapurkar Samadhan G Kshirsagar Brijesh K Sutariya Maulik S Patel Hiren M Patel Dheerendra K Pandey Rajesh H Bahekar Mukul R Jain 

作者机构：Department of Pharmacology and ToxicologyZydus Research CentreCadila Healthcare Limited 

出 版 物：《World Journal of Diabetes》 (世界糖尿病杂志（英文版）（电子版）)

年 卷 期：2018年第9卷第6期

页      面：80-91页

核心收录：

学科分类：10[医学] 

主　　题：Coagonist Glucagon Renal dysfunction Glucagon-like peptide-1 Insulin sensitivity 

摘      要：AIM To investigate the role of glucagon-like peptide-1(GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS Chronic high-fat diet fed C57 BL/6 J mice, streptozotocintreated high-fat diet fed C57 BL/6 J mice and diabeticC57 BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocintreated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist(Aib2 C24 Chimera2, 150 μg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes(SREBP-1 C, FAS, and SCD-1) was decreased, and expression of genes involved in β-oxidation(CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-?. Coagonist treatment reduced expression of inflammatory(TNF-α, MCP-1, and MMP-9) and pro-fibrotic(TGF-β, COL1 A1, and α-SMA) genes and also improved histological derangement in renal *** Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia.