Sodium requirement for insulin release: putative role in regulation of intracellular pH.
The effects on insulin release of Na+ removal, alteration of extracellular pH, and inhibition of acid extrusion processes were examined using freshly isolated and 46-h cultured islets of Langerhans. Na+ removal inhibited the secretory response to 16.7 mM glucose specifically in fresh islets but stimulated the low-glucose response in cultured islets. These divergent effects of Na+ depletion were perfectly mimicked by amiloride, an inhibitor of Na+-H+ exchange, and could be overcome in a raised HCO-3, pH 8.0 medium. Simply raising extracellular pH at constant HCO-3 had no effect. Na+ removal also inhibited the secretory responses to other nutrient secretagogues such as D-glyceraldehyde and L-leucine but not to agents like 3-isobutyl-1-methylxanthine or 12-O-tetradecanoylphorbol-13-acetate. The results show that Na+ is not itself essential for the secretory process but rather suggest that it plays a permissive role in the regulation of intracellular pH via Na+-H+ exchange. Such a regulation appears important mainly for nutrient-stimulated insulin release, which is associated with the generation of acidic metabolites.
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism*; D046508:Culture Techniques; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology*; D013268:Stimulation, Chemical
D001639:Bicarbonates; D007328:Insulin; D000584:Amiloride; D012964:Sodium; D005947:Glucose