The Effect Of M617 On The Translocation Of GLUT4 In T2DM Rats' Skeletal Muscle

Objects: To explore the relationship between GALR1 and insulin sensitivity, and between GALR1 and the translocation of GLUT4 in cell membranes of skeletal muscles and among GALR1, GLUT4 and type 2 diabetes by using M617, a type 1 galanin receptor agonist.Methods: 3-4 week old SD rats were fed with standards diets for 2 weeks. Then selected 10 rats randomly as a healthy control group to keep on feeding with the standards diet, and the remains changed to high-fat diet. Eight weeks later, the laters were injected with STZ 40mg/kg (i.p.). After the model of type 2 diabetes was established successfully, the model rats were randomly divided into 2 groups, one for diabetic control group and the other for diabetic drug group. Each group contain 10 rats, male and female,half of each. Rats in both control groups were injected (i.p.) with saline (0.3 mL/d), and the diabetic drug group with M617 for 20 days consecutively. Body weight of all rats was measured by electronic scale. Blood sugar level was determined using One touch Sure Step Blood Glucose meter. Serum insulin levels, galanin levels and GLUT4 contents in skeletal muscle were detected by ELISA method. Insulin sensitivity was got through high insulin- euglycemic clamp texsts. The total protein of GLUT4 expressed in muscle homogenate was measured by Western Blot method and GLUT4 mRNA quantity in skeletal muscle was detected through Real time PCR.Results: The results showed that serum insulin and galanin levels increased significantly in both diabetic groups contrasted to the healthy control group. However, insulin sensitivity, GLUT4 mRNA expression, GLUT4 total protein levels in skeletal muscles and the quantity of GLUT4 translocation onto plasma membranes of muscle cells decreased significantly. M617 treatment decreased the serum insulin levels significantly, but elevated blood glucose levels, glucose infusing rates in insulin- euglycemic clamp texsts and the quantity of GLUT4 translocation onto plasma membrane of the cells significantly, While the serum galanin content, GLUT4 mRNA expression and GLUT4 protein levels in skeletal muscles were no significant different in the diabetic drug group compared with the diabetic control group.Conclusions: T2DM models, established by feeding high-fat diet and an intraperitoneal injection of low doze of STZ, showed enhanced insulin resistance and reduced levels of the GLUT4 protein in skeletal muscle and GLUT4 translocation onto plasma membranes of muscle cells. M617 promoted insulin sensitivity and increased GLUT4 translocation onto plasma membranes of the cells. Thus it improved the ability of glucose intake in muscle cells. These results suggested that galanin may elevate the insulin sensitivity by promoting GLUT4 translocation from intracellular membranes to plasma membranes in muscle cells through GALR1. GALR1 specific agonists may be taken as a new kind of drugs to treat T2DM.