title: Recruitment of GLUT-4 glucose transporters by insulin in diabetic rat skeletal muscle.
abstract: The cause of reduced insulin-stimulated glucose transport in skeletal muscle of diabetic rats was investigated. Basal and insulin-stimulated glucose uptake into hindquarter muscles of 7-day diabetic rats were 70% and 50% lower, respectively, than in nondiabetic controls. Subcellular fractionation of hindquarter muscles yielded total crude membranes, plasma membranes and intracellular membranes. The number of GLUT-4 glucose transporters was lower in crude membranes, plasma membranes and intracellular membranes, relative to non-diabetic rat muscles. These results were paralleled by reductions in D-glucose-protectable binding of cytochalasin B. Insulin caused a redistribution of GLUT-4 transporters from intracellular membranes to plasma membranes, in both control and diabetic rat muscles. This redistribution was also recorded using binding of cytochalasin B. The insulin-dependent decrement in glucose transporters in intracellular membranes was similar for both animal groups, but the gain and final amount of transporters in the plasma membrane were 50% lower in the diabetic group. The results suggest that insulin signalling and recruitment of GLUT-4 glucose transporters occur in diabetic rat muscle, and that the diminished insulin response may be due to fewer glucose transporters operating in the muscle plasma membrane.
authors.affiliation: Division of Cell Biology, Hospital for Sick Children, Toronto, Ont., Canada.
authors.forename: A
authors.initials: A
authors.lastname: Klip
authors.forename: T
authors.initials: T
authors.lastname: Ramlal
authors.forename: P J
authors.initials: PJ
authors.lastname: Bilan
authors.forename: G D
authors.initials: GD
authors.lastname: Cartee
authors.forename: E A
authors.initials: EA
authors.lastname: Gulve
authors.forename: J O
authors.initials: JO
authors.lastname: Holloszy
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D003571:Cytochalasin B / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
chemical_list: D007328:Insulin; D009004:Monosaccharide Transport Proteins; D003571:Cytochalasin B