Supramaximal decrease of sulphonylurea-induced accumulation of sodium in pancreatic islets.
Sodium was measured in beta-cell-rich pancreatic islets of mice under steady state conditions or after 6 min of exposure to 1 mM ouabain. The islet content of sodium increased when 100 microM tolbutamide or 1 microM glipizide were added to an albumin-containing (1 mg ml-1) medium, but remained unaffected at 10-fold higher concentrations. Both sulphonylurea compounds promoted the uptake of Na+ in the presence of ouabain. Whereas tolbutamide was stimulatory at 10 microM or above in a medium containing 10 mg ml-1 albumin, only 0.1 microM was required in the absence of albumin. In the latter situation there was a reduction of the stimulatory action with increase of the tolbutamide concentration from 100 to 1000 microM. The inhibitory component in the sulphonylurea action on the Na+ uptake was particularly impressive with glipizide, maximal stimulation being reached at 10 microM in the presence of 1 mg ml-1 albumin. Diazoxide (400 microM) modified the glipizide action on Na+ uptake, making 1000 microM stimulatory instead of 1 microM. The latter concentration of glipizide became inhibitory after removal of K+. Glipizide stimulated the Na+ uptake both at low and high concentrations in a medium deficient in Ca2+ or when the cotransport of Na+, K+ and Cl- was blocked by 20 microM bumetanide. The observation that the sulphonylurea-induced islet accumulation of sodium is diminished at supramaximal concentrations reinforces existing arguments for additional effects of high concentrations of hypoglycemic sulphonylureas.
Saha
S
S
Department of Medical Cell Biology, University of Uppsala, Sweden.
Hellman
B
B
D000818:Animals; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010042:Ouabain / Q000494:pharmacology*; D010783:Photometry; D012964:Sodium / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000494:pharmacology*
D007328:Insulin; D013453:Sulfonylurea Compounds; D010042:Ouabain; D012964:Sodium