Stimulation of insulin release by D-glucose in depolarized pancreatic islets.
This study reevaluates the relevance of plasma membrane depolarization in the pancreatic islet B-cell to the stimulation of insulin release by D-glucose. In rat pancreatic islets exposed to increasing concentrations of D-glucose, a sigmoidal relationship is observed between the output of insulin and concentration of the hexose. The release of insulin recorded in the absence of D-glucose or at a non-stimulatory concentration (2.5 mM) of the hexose is significantly enhanced when the islets are incubated in the presence of the meglitinide analogue A-4166 (20 microM) or at a high concentration (30 microM) of extracellular K+. Nevertheless, even in the presence of A-4166 or at the high K+ concentration, increasing concentrations of D-glucose, up to 20 microM, still enhance, in a sigmoidal manner, the secretion of insulin, with a 15-fold or greater increment in insulin output relative to the value found in the absence of the hexose. These findings indicate that D-glucose provides a concentration-related signal for insulin release, that cannot be attributed solely to either the closing of ATP-sensitive K+ channels, the depolarization of the plasma membrane, or the role of D-glucose as a nutrient to cover the energy expenditure in the islet cells.
Malaisse
W J
WJ
Laboratory of Experimental Medicine, Erasmus School of Medicine, Brussels Free University, Belgium.
D000818:Animals; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats
D003510:Cyclohexanes; D007328:Insulin; D015221:Potassium Channels; D000077715:Nateglinide; D010649:Phenylalanine; D005947:Glucose