Do hypoglycemic sulfonylureas inhibit Na+,K+-ATPase activity in pancreatic islets?
The view that the insulinotropic response to hypoglycemic sulfonylureas is somehow related to an inhibitory action of these drugs on either the Ca2+-activated K+ permeability or the Na+,K+-ATPase activity in pancreatic islet cells was investigated by measuring the effect of tolbutamide on 86Rb outflow and uptake, 45Ca outflow, and insulin release in rat pancreatic islets. Although tolbutamide inhibited 86Rb efflux from glucose-deprived islets, whether in the absence or presence of extracellular Ca2+ or ouabain, a primary action of the sulfonylurea on the Ca2+-responsive K+ channels appeared unlikely, because tolbutamide failed to suppress the increase in 86Rb outflow evoked by either the ionophore A23187 or ouabain. Glibenclamide also failed to suppress the increase in 86Rb outflow evoked by the ionophore. Moreover, tolbutamide itself stimulated quinine-sensitive 86Rb outflow from glucose-stimulated islets. Likewise, although tolbutamide inhibited an ouabain-resistant modality of 86Rb inflow into the islet cells, an inhibitory action of the sulfonylurea on the Na+,K+-ATPase appeared improbable, because tolbutamide failed to minimize and instead favored the cationic and secretory response to ouabain. It is concluded, therefore, that the capacity of tolbutamide to cause under suitable conditions continuous electrical activity in islet cells cannot be attributed to inhibition of either the Ca2+-sensitive K+ permeability or ouabain-sensitive Na+,K+-ATPase.
Lebrun
P
P
Malaisse
W J
WJ
Herchuelz
A
A
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D007515:Islets of Langerhans / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology; D051381:Rats; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014044:Tolbutamide / Q000494:pharmacology*
D007328:Insulin; D007473:Ion Channels; D000001:Calcimycin; D010042:Ouabain; D014044:Tolbutamide; D011803:Quinine; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D012413:Rubidium; D011188:Potassium; D005905:Glyburide; D002118:Calcium