Fat cells: model system to investigate molecular mechanism(s) of sulfonylurea-potentiated glucose transport.
The cellular mechanism of action of sulfonylureas may vary depending upon the exact nature of the drug, the tissue or cell type in question, and the status of the subject from which it was obtained. In adipocytes from patients with type II non-insulin-dependent diabetes, there is increasing evidence indicating that sulfonylureas ameliorate a post-receptor defect in insulin action by potentiating the insulin-stimulated glucose transport normally seen in these cells. Studies undertaken to elucidate the molecular mechanism of this potentiation investigated the effects of a 48-hour incubation with glyburide (2 micrograms/ml) on the recruitment of glucose carriers from microsomal storage pools to the plasma membrane. With the use of cytochalasin B, a potent competitive inhibitor of glucose transport, glucose-sensitive cytochalasin B binding was studied in basal and insulin-stimulated adipocytes from control and sulfonylurea-treated tissue. The data indicated that sulfonylurea treatment did not affect the total glucose-sensitive cytochalasin B binding capacity of adipocyte membranes. It did, however, increase the insulin-induced recruitment of the glucose carrier from the microsome to the plasma membrane by 27 to 31 percent. This suggests that the molecular mechanism of sulfonylurea-enhanced insulin-stimulated glucose transport is the recruitment of glucose transporters from an intracellular microsomal storage pool to the plasma membrane.
D000273:Adipose Tissue / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D002462:Cell Membrane; D003571:Cytochalasin B / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008861:Microsomes
D001786:Blood Glucose; D007328:Insulin; D003571:Cytochalasin B; D005905:Glyburide