Effect of exendin-4 treatment upon glucose uptake parameters in rat liver and muscle, in normal and type 2 diabetic state.
Exendin-4, like GLP-1, is insulinotropic, antidiabetic and glucoregulatory among other properties, which are thought to be exerted through the pancreatic GLP-1 receptor; exendin-4 is also an agonist of the GLP-1 stimulatory action upon liver and muscle glucose metabolism, where GLP-1 receptor is distinct from that in the pancreas. We investigated the action of prolonged treatment with exendin-4 upon glucose transport parameters in skeletal muscle and liver of normal rats and streptozotocin-induced type 2 diabetic rats (T2D). Muscle of T2D showed lower than normal glucose transport; exendin-4 did not modify the value in normal but normalized that in the T2D; unlike previously detected with GLP-1, no apparent modification was observed in GLUT-4 expression in either group after exendin-4, except for an increased GLUT-4 protein in normal rats. Yet, exendin-4 significantly stimulated liver GLUT-2-mRNA and -protein in T2D and normal rats, the effect upon GLUT-2-protein in T2D being higher than that in normal animals; this was accompanied by a normalizing action of exendin-4 upon the lower than normal liver glycogen in T2D rats. These data suggest that the liver may represent at least one of the major target organs for exendin-4 to exert its plasma lowering effect in diabetic state.
Arnés
Luis
L
Department of Metabolism, Nutrition and Hormones, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040-Madrid, Spain.
Moreno
Paola
P
Nuche-Berenguer
Bernardo
B
Valverde
Isabel
I
Villanueva-Peñacarrillo
Maria L
ML
D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology*
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D006003:Glycogen; D000077270:Exenatide; D005947:Glucose