The Effect Of M871and M1145on Transportation Of GLUT4on DM Rats’ Skeletal Muscle

Objective:In order to explore the relationship between GALR2and GLUT4quantity and transposition in cell membranes of skeletal muscles; Use GALR2antagonist M871and GALR2speculate agonist M1145to explore relationship between GALR2, insulin sensitivity and Diabetes metabolism. In order to explore the relationship among galanin, GLUT4and diabetes.Methods:Selected Healthy Wistar rats were fed with standards diets for2weeks.,then selected rats that weight is higher then200g become the esperimental objects. Selected10rats randomly as a healthy control group to keep on feeding with the standards diet, and the remainswere injected with STZ STZ)35+15+10mg/kg(i.p.). After the model of diabetes was established successfully, the model rats were randomly divided into3groups, one for diabetic control group and the others for diabetic drug group. Each group contain10rats, male and female, half of each. Rats in control group were injected (i.p.) with Liquid of Cerebro-spinal (5μL/d), and the diabetic drug group with M817and M1145(5μL/d) for15days 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 GLUT4contents in skeletal muscle were detected by ELISA method. Insulin sensitivity was got through high insulin-euglycemic clamp texsts. The total protein of GLUT4expressed in muscle homogenate was measured by Western Blot method and GLUT4mRNA quantity in skeletal muscle was detected through Real time PCR.Results:The central administration of M1145significantly enhanced GLUT4mRNA expression level, GLUT4contents (p<0.05) and translocation quantity (p<0.05), infusing speed rates in euglycemic clamp tests (P<0.05), but reduced body weight and blood sugar level in the diabetic agonist group as compared with diabetic control. There were not significant differences in the serum insulin level of animals. Contrarily, M817in brain pronouncedly attenuated GLUT4mRNA expression level, infusing speed rates (P<0.05), GLUT4contents (p<0.05) and translocation quantity (p<0.05), whereas elevated the serum insulin level (p<0.05) in the diabetic agonist group as compared with diabetic control. There were similar trends observed in diabetic control groups compared with healthy control (P<0.05&P<0.01).Conclusions:GALR2agonist M1145injected intracerebroventricularly increased insulin sensitivity and GLUT4translocation to plasma membrane of myocytes to accelerate glucose uptake. Whereas, central administration of GALR2antagonist M871decreased insulin sensitivity and GLUT4trafficking to plasma membrane of myocytes to impede glucose uptake. The STZ-induced diabetic models showed an enhanced insulin resistance, but reduced GLUT4content and GLUT4translocation in myocytes of rats. These suggest that central GALR2plays an important role in regulating glucose metabolism and glucose homeostasis in vivo and the GALR2specific agonist may be a novel drug for reducing insulin resistance.