Effect of GLP-1 treatment on GLUT2 and GLUT4 expression in type 1 and type2 rat diabetic models

Glucagon-like peptide-1 (GLP-1) is an incretin with glucose-dependent insul inotropic and insulin-independent antidiabetic properties that exerts insul in-like effects on glucose metabolism in rat liver, skeletal muscle, and fa t. This study aimed to search for the effect of a prolonged treatment, 3 ds , with GLP-1 on glucotransporter GLUT2 expression in liver, and on that of GLUT4 in skeletal muscle and fat, in rats. Normal rats and streptozotocin-i nduced type 1 and type 2 diabetic models were used; diabetic rats were also treated with insulin for comparison. In normal rats, GLP-1 treatment reduc ed in the three tissues the corresponding glucotransporter protein level, w ithout modifying their mRNA. In the type 2 diabetic model, GLP-1, like insu lin, stimulated in liver and fat only the glucotransporter translational pr ocess, while in the muscle an effect at the GLUT4 transcriptional level was also observed. In the type 1 diabetic model, GLP-1 apparently exerted in t he liver only a posttranslational effect on GLUT2 expression; in muscle and fat, while insulin was shown to have an action on GLUT4 at both transcript ional and translational levels, the effect of GLP-1 was restricted to gluco transporter translation. In normal and diabetic rats, exogenous GLP-1 contr olled the glucotransporter expression in extrapancreatic tissues participat ing in the overall glucose homeostasis-liver, muscle, and fat-where the eff ect of the peptide seems to be exerted only at the translational and/or pos ttranslational level; in muscle and fat, the presence of insulin seems to b e required for GLP-1 to activate the transcriptional process. The stimulati ng action of GLP-1 on GLUT2 and GLUT4 expression, mRNA or protein, could be a mechanism by which, at least in part, the peptide exerts its lowering ef fect on blood glucose.