Effect of GLP-1 treatment on GLUT2 and GLUT4 expression in type 1 and type 2 rat diabetic models

• Published in: Endocrine Vol. 15; no. 2; pp. 241 - 248
• Main Authors: Villanueva-Peñacarrillo, M L, Puente, J, Redondo, A, Clemente, F, Valverde, I
• Format: Journal Article
• Language: English
• Published: United States 01.07.2001
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Blotting, Northern; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - metabolism; Gene Expression - drug effects; Glucagon - pharmacology; Glucagon-Like Peptide 1; Glucose - metabolism; Glucose Transporter Type 2; Glucose Transporter Type 4; Liver - drug effects; Liver - metabolism; Male; Monosaccharide Transport Proteins - genetics; Muscle Proteins; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Peptide Fragments - pharmacology; Protein Precursors - pharmacology; Rats; Rats, Wistar; RNA, Messenger - analysis
• ISSN: 1355-008X
• DOI: 10.1385/ENDO:15:2:241

Glucagon-like peptide-1 (G LP-1) is an incretin with glucose-dependent insulinotropic and insulin-independent antidiabetic properties that exerts insulin-like effects on glucose metabolism in rat liver, skeletal muscle, and fat. 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-induced type 1 and type 2 diabetic models were used; diabetic rats were also treated with insulin for comparison. In normal rats, GLP-1 treatment reduced in the three tissues the corresponding glucotransporter protein level, without modifying their mRNA. In the type 2 diabetic model, GLP-1, like insulin, stimulated in liver and fat only the glucotransporter translational process, 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 the liver only a posttranslational effect on GLUT2 expression; in muscle and fat, while insulin was shown to have an action on GLUT4 at both transcriptional and translational levels, the effect of GLP-1 was restricted to glucotransporter translation. In normal and diabetic rats, exogenous GLP-1 controlled the glucotransporter expression in extrapancreatic tissues participating in the overall glucose homeostasis-liver, muscle, and fat-where the effect of the peptide seems to be exerted only at the translational and/or posttranslational level; in muscle and fat, the presence of insulin seems to be required for GLP-1 to activate the transcriptional process. The stimulating 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 effect on blood glucose.