葡萄糖激酶
内科学
内分泌学
餐后
脂肪变性
葡萄糖稳态
兴奋剂
2型糖尿病
胰岛素
医学
糖尿病
化学
受体
胰岛素抵抗
作者
Nirav Dhanesha,Amit Joharapurkar,Gaurang Shah,Samadhan Kshirsagar,Vishal Patel,Kuldip R. Patel,Rajesh Bahekar,Mukul Jain
标识
DOI:10.1016/j.ejphar.2013.06.015
摘要
The glucokinase activators improve the fasting as well as postprandial glucose control and are important investigational drugs for the treatment of diabetes. However, recent studies have implicated that continuous activation of glucokinase with a small molecule activator can increase hepatic triglycerides and the long term glucose control is not achieved. In this study, we investigated the effect of combination of glucokinase activator (GKA, Piragliatin) with GLP-1 receptor agonist exendin-4 (Ex-4) in male db/db mice. Twelve weeks combination treatment in the db/db mice resulted in a significant decrease in body weight gain, food consumption, random glucose and %HbA1c. The decrease in serum glucose and %HbA1c in combination group was more profound and significantly different than that of individual treatment (GKA or Ex-4) group. GKA treatment increased hepatic triglycerides, whereas combination of Ex-4 with GKA attenuated hepatic steatosis. The combination of GKA with Ex-4 reduced the hepatic lipid accumulation, improved the insulin sensitivity, and reduced hepatic glucose production in db/db mice. Overall, our data indicate that combination of GKA and GLP-1 receptor agonist Ex-4 improves glucose homeostasis, shows antiobesity activity, without causing harmful side effects like fatty liver.
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