The Effect Of M871 On Translocation Of GLUT4 In Adipocytes Of T2DM Rats

Objective: To explore the effect of type 2 galanin receptor (GALR2) antagonist M871 on the glucose transporter 4(GLUT4) membrane translocation in adipocytes of type 2 diabetic rats in the conditions of blocking the role of endogenous GALR2,in order to understand the relationship between GALR2 and lipid metabolic disorder and insulin sensitivity.Methods: Sprague-Dawley rats were fed with the high fat diet for eight weeks. The rats over 200g were treated by one injection of streptozotocin (40mg/kg,i.p.) to establish type 2 diabetic models. The model rats were randomly divided into control and drug groups. Rats from diabetic control group (n=10) and healthy control group (n=10) were injected by saline vehicle (0.3mL/d,i.p.) for twenty days. Rats from the diabetic drug group (n=10) by M871 (3μmol/kg/d). The insulin sensitivity of the three group rats was investigated by the euglycemic clamp tests, blood glucose levels by a plasma glucose instrumental, fasting serum insulin, galanin, RBP4, PPARγlevels and GLUT4 content in adipose tissue homogenate by ELASA kits, GLUT4 contents in adipocyte membranes by Western blot method, GLUT4 mRNA levels of adipose tissue by Real-time PCR.Results: Relative to diabetic controls, diabetic drug group animals displayed enhensed glucose infusing rates in the euglycemic clamp tests (P<0.05), blood glucose (P<0.05) and RBP4 levels (P<0.01). But PPAR-γlevels (P<0.05) and GLUT4 contents (P<0.05) at plasma membranes were reduced. Meanwhile, there was not significant difference in animal weight, serum insulin and GAL levels, GLUT4 mRNA expression and total GLUT4 contents of adipocytes.Conclusions: M871,a special GALR2 antagonist,elevated blood glucose and RBP4 levels, reduced PPARγsecretion and GLUT4 translocation onto the plasma membranes. Thus it induced lipid metabolic disorder and insulin resistance. These findings provided evidences to support that GALR2 mediates the effect of galanin on regulation of lipid metabolism and improvement over lipid metabolic disorder and insulin resistance. GALR2 may become a new focus of treatment for type 2 diabetes.