Insulinotropic effects of hypoglycaemic and hyperglycaemic sulphonamides: the ionophoretic hypothesis.
Hypoglycaemic sulphonamides stimulate net uptake of 45Ca++ and insulin release in isolated pancreatic islets. These effects are antagonized by organic calcium-antagonists (e.g. suloctidil). In an artificial system, hypoglycaemic sulphonamides, such as gliclazide, stimulate the translocation of calcium into or across a hydrophobic immiscible domain, a process enhanced by the antibiotic ionophore A 23187 and antagonized by suloctidil. In this artificial system, the A 23187-mediated process of calcium countertransport is stimulated by gliclazide and inhibited by diazoxide. It is postulated that the insulinotropic action of hypoglycaemic and hyperglycaemic sulphonamides is primarily attributable to the ionophoretic action of these drugs.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005907:Gliclazide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007476:Ionophores; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D013468:Suloctidil / Q000494:pharmacology*
D007328:Insulin; D007476:Ionophores; D011412:Propanolamines; D013453:Sulfonylurea Compounds; D000001:Calcimycin; D005907:Gliclazide; D002118:Calcium; D013468:Suloctidil