monensin and Hyperglycemia

Vascular endothelial cells, which are polyfunctional, play an important role in the pathogenesis of diabetic complications. The increase in vascular permeability, ie, regulated by vascular endothelial cells, has been reported in patients with diabetes mellitus complicated by angiopathy. To determine the role of hyperglycemia in endothelial cell permeability, we examined the effect of high concentrations of glucose on the permeability of cultured bovine aortic endothelial cells. The permeations of albumin and fluorescein-labeled dextran (FD) across endothelial cell monolayers were increased when cultured with a high concentration of glucose (400 mg/dL). This increased permeation of albumin but not FD was temperature-dependent and was partially reduced by adding 100 mumol/L ponalrestat (ICI 128,436, Statil; ICI, Cheshire, UK), which is an aldose reductase inhibitor. Stimulation or inhibition of Na,K-adenosine triphosphatase (ATPase) in bovine aortic endothelial cells failed to alter their permeability. These findings suggest that high concentrations of glucose enhance transendothelial permeability of albumin in part by activating the polyol pathway, but independently of Na,K-ATPase activity.

Topics: Animals; Capillary Permeability; Cattle; Dextrans; Endothelium, Vascular; Fluorescein; Fluoresceins; Glucose; Hyperglycemia; Mannitol; Monensin; Osmolar Concentration; Ouabain; Serum Albumin; Sorbitol; Temperature

Glibenclamide, a second generation sulfonylurea, is an oral hypoglycemic drug. It seems to act mainly on the ATP-driven K(+)- channels of the beta-cells of pancreas determining insulin secretion. Because monensin, a Na+/H+ antiport, is able when administered to rats in vivo to inhibit insulin secretion, the action of glibenclamide is studied on glycemia and insulinemia to verify if it can antagonize the action of monensin. The results show that glibenclamide is able to partly reverse ionophore induced hyperglycemia and the inhibition of insulin secretion. These results might be interpreted as if glibenclamide only reverses the ATP-driven K(+)- channel dependent insulin secretion. Moreover the antagonist action of glibenclamide is slightly delayed when both drugs are administered together. The role of Na+/H+ antiport in basal insulin secretion is discussed.

Topics: Animals; Blood Glucose; Female; Glyburide; Hyperglycemia; Insulin; Insulin Secretion; Monensin; Rats; Rats, Sprague-Dawley