| Objective:As a secretin, the glucagon-like peptide 1 (GLP-1) can increases tissue glucose uptake and causes vasodilation independent of insulin. The current study show that GLP-1 also can increase muscle sensitivity by improve muscle micro vascular. But there’s no report showed that GLP-1 do the same improving effect on type 2 diabetic rat with insulin resistance. To investigate the mechanism of Glucagon-like peptide 1 (GLP-1) acted with insulin sensitivity in obese type 2 diabetic rats.Methods:The rats were randomized into type 2 diabetes mellitus group(T2DM group), type 2 diabetes mellitus with GLP-1 intervention group(T2DM+GLP-1 group) and normal control group(NC group). Rats of T2DM group and T2DM+GLP-1 group fed high fat diet and NC group normal diet for four weeks. The two groups of which fed high fat diet were induced by intraperitoneal injection of streptozotocin(STZ, 30mg/kg) to established type 2 diabetes mellitus model. Every subjects were recieved hyperinsulinemic-euglycemic clamps after overnight fasting. The T2DM+GLP-1 group were infusioned GLP-1(30pmol/Kg/min) for 30min first before the hyperinsulinemic-euglycemic clamps experiment started. The glucose infusion rate in 120min and pick up blood sample for insulin concentration every 30min rial were measured in Hyperinsulinemic-euglycemic clamps. The mean arterial pressure was measured during the clamps every ten minutes. The Gastrocnemius Serine/threonine protein kinase(Akt) phosphorylation was measured by Western blot.Results:Compared with that of NC group, the glucose infusion rate in 120min of T2DM group was lowered (P<0.05), the skeletal muscle Akt phosphorylation levels of T2DM group were decreased(P<0.01). Compared with T2DM group, the glucose infusion rate in 120min of T2DM+GLP-1 group was raised (P<0.05), so do the Akt phosphorylation levels of skeletal muscle in T2DM+GLP-1 group (P<0.01). After GLP-1 infusion for 30min, the mean arterial pressure T2DM+GLP-1 group was lowered (P<0.01). There’s no difference of insulin concentration among three groups (P>0.05).Conclusions:GLP-1 increases glucose uptake and improves insulin sensitivity of skeletal muscle in tranquility status of type 2 diabetes rats by the skeletal muscle Akt phosphorylation levels. This action of GLP-1 is not with an increase of blood insulin concentration. GLP-1 can also effect the mean arterial pressure on obese type 2 diabetic rats... |
