Preserved GLP-I Effects on Glycogen Synthase a Activity and Glucose Metabolism in Isolated Hepatocytes and Skeletal Muscle From Diabetic Rats

To search if biological effects of GLP-I on glucose metabolism in extrapancreatic tissue are present in diabetic states, we have studied the action of GLP-I and insulin on glycogen-enzyme activity, glycogen synthesis, and glucose metabolism in isolated hepatocytes and soleus muscle from adult streptozotocin (STZ)- and neonatal STZ- treated diabetic rats. This work confirms the previously reported insulin-like effects of GLP-I on glucose metabolism in both muscle and liver tissue from normal rats (control). The present study extends those observations to the muscle and liver tissue of diabetic animals. In both muscle and liver tissue, the metabolism of d-glucose, in the absence of added peptides, was more severely affected in adult STZ (IDDM model) than in neonatal STZ (nSTZ; NIDDM model) rats, and the magnitude of hormonal effect on metabolic variables was lower in diabetic rats than in control rats, as a rule. Nevertheless, in liver and muscle tissue of diabetic rats, GLP-I was able to increase glycogen synthase activity, augment the net rate of d-[U-¹⁴C]glucose incorporation into glycogen, and increase d-[5-³H]glucose utilization, d-[U-¹⁴C]glucose oxidation, and lactate production. In conclusion, GLP-I exerts insulin-like effects on d-glucose metabolism in both muscle and liver tissue in IDDM or NIDDM animal models, and present observations reinforce the view that GLP-I may represent a most promising tool in the treatment of diabetic patients.