ABSTRACT
The Goto-Kakizaki (GK) rat is a spontaneous type 2 diabetic animal model, which is characterized by a progressive loss of beta islet cells with fibrosis. In the present study, the hypoglycemic effect of asiatic acid (AA) in GK rats was examined. GK rats receiving AA at a daily dose of 25 mg·kg(-1) for four weeks showed a significant reduction in blood glucose levels. Age-matched normal Wistar rats were given 0.5% sodium carboxymethyl cellulose (CMC-Na) solution for the same periods and used as control. Compared to the normal Wistar rats, GK rats treated with AA showed improvement in insulin resistance partially through decreasing glucose level (P < 0.01) and insulin level (P < 0.05). Furthermore, the results of immunohistochemistry indicate that AA treatment reduced islet fibrosis in GK rats. Fibronectin, a key protein related to islet fibrosis, was over-expressed in GK rats, which was reversed significantly by AA treatment (P < 0.05). These findings suggest that AA has a beneficial effect on lowering blood glucose levels in GK rats and improves fibrosis of islets in diabetes, which may play a role in the prevention of islets dysfunction.
Subject(s)
Animals , Male , Blood Glucose , Metabolism , Centella , Chemistry , Diabetes Mellitus, Type 2 , Drug Therapy , Pathology , Disease Models, Animal , Fibronectins , Metabolism , Fibrosis , Glucose Tolerance Test , Hyperglycemia , Drug Therapy , Pathology , Insulin , Blood , Insulin Resistance , Islets of Langerhans , Pathology , Pancreatic Diseases , Metabolism , Pathology , Pentacyclic Triterpenes , Pharmacology , Therapeutic Uses , Phytotherapy , Plant Extracts , Pharmacology , Therapeutic Uses , Rats, Inbred StrainsABSTRACT
Pancreatic stellate cell (PSC) activation in islet fibrosis of insulin-resistant rats induced by high-fat diet was investigated. After 20 weeks, the glucose infusion rate and glucose-stimulated insulin secretion in high-fat group were significantly decreased while fasting plasma glucose, fasting serum insulin, free fatty acid and the basal glucagon secretion were significantly increased compared with those parameters of the control rats (P< 0.05 or P<0.01). Activated PSC and collagen fiber ( type Ⅰ and Ⅲ) were found in islets of rats fed with high-fat. The result suggests that PSC activation, proliferation and migration to islet may contribute to islet fibrosis in insulin-resistant rats.