The Effect Of M871 On Transportation Of GLUT4 In Skeletal Muscles Of T2DM Rats

Objective: To explore the effect of type 2 galanin receptor (GALR2) antagonist M871 on the glucose transporter 4(GLUT4) membrane transportation in skeletal muscle cells, in order to understand the the relationship between GALR2 and insulin sensitivity in type 2 diabetic rats.Method: From 6-week-old male SD rats, twenty rats were randomly selected as normal sedentary and trained control groups and were fed with normal standard diet. The remains were fed with high-fat and high-carbohydrate diet for 6 weeks and then were injected with streptozotocin(35mg/kg)though abdominal cavity to establish animal models of type 2 diabetes. The model rats were randomly divided into four groups: model sedentary control, model trained control, model sedentary drug and model trained drug groups. The modle rats were continued to be fed with high-fat and high-charbohydrate diet. Rats from model sedentary and model trained drug groups were injected by M871(3μmol/kg/d),a type 2 galanin receptor antagonist for 20 days,rats from all control groups by 0.3 mL/d sodium chloride. Rats from the tree exercise groups swam 1h/d after each injection. During the experiment, the body weights of all animals were measured by an electronic scale per week. Blood glucose levels of all rats were determined by using One Touch Sure Step Blood Glucose Meter. GLUT4 contents in skeletal muscles, serum insulin and galanin levels were detected by ELISA method. Insulin sensitivity was got through high insulin- euglycemic clamp texsts. The GLUT4 contents in plasma membranes and in homogenate of muscles were measured by Western Blot method,and GLUT4 mRNA quantity in skeletal muscles was detected by Real-time PCR. Result: The results showed that M871 reduced glucose infusing rate in euglycemic-hyperinsulinemic clamp tests and GLUT4 content at plasma membranes, but elevated the blood glucose levels in both diabetic drug groups compared with each diabetic control group. And blood glucose and serum insulin levels were significantly reduced in the exercises groups compared with each sedentary controls. Meanwhile, swimming enhanced serum galanin levels and glucose infusing rate, increased GLUT4 mRNA expression, elevated GLUT4 contents in homogenate and at plasma membranes of skeletal muscle cells.Conclusion: GALR2 antagonist M871 decreases glucose uptake capacity and insulin sensitivity of type 2 diabetic animals. It does not significantly change total GLUT4 contents in skeletal muscle cells, but reduces GLUT4 transportation quantity to plasma membranes. This result implicates that endogenous galanin may accelerate GLUT4 translocation from intracellular membranes to cell surfaces and elevate insulin sensitivity via GALR2. GALR2 may become a new target to treat type 2 diabetes.