Sulfonylureas mimic glucose in stimulating the uptake of Na+ in pancreatic islets exposed to ouabain.
The increase of sodium in response to ouabain inhibition of the Na+/K+ pump was measured in beta-cell-rich pancreatic islets from ob/ob mice using integrating flame photometry. D-Glucose promoted the uptake of sodium when added at a concentration of 6 mM or above. The hypoglycemic sulfonylurea compound, tolbutamide, mimicked the action of D-glucose in stimulating the sodium uptake at concentrations of 10 microM or above. There was no stimulation beyond that obtained with 20 mM glucose during exposure to 100 microM tolbutamide. Other test substances also affected sodium uptake in a way reflecting known effects on insulin release. Accordingly, the sodium uptake was stimulated with glibenclamide, glipizide, HB 699 (4-[2-(5-chloro-2-methoxybenzamido)ethyl]benzoic acid) and high K+. Sulphonamides (sulfamethazole, sulfadiazine and sulfadoxine) had practically no effect when added at a concentration of 1 mM. Sodium uptake in response to glucose and tolbutamide was antagonized by 400 microM diazoxide or 4 microM tetrodotoxin. It is concluded that both glucose and hypoglycemic sulfonylureas stimulate Na+ entry into the pancreatic beta-cells, a process presumably involving depolarization.
Saha
S
S
Department of Medical Cell Biology, University of Uppsala, Sweden.
Hellman
B
B
D000818:Animals; D005947:Glucose / Q000494:pharmacology*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010042:Ouabain / Q000494:pharmacology*; D010783:Photometry; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013424:Sulfanilamides / Q000494:pharmacology; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D013424:Sulfanilamides; D013453:Sulfonylurea Compounds; D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose