Glucose-stimulated insulin secretion: A newer perspective

摘要: Existing concepts and models for glucose-stimulated insulin secretion (GSIS) are overviewed a newer perspective has been formulated toward the physiological understanding of GSIS. A conventional model created on basis in vitro data application square wave high glucose absence any other stimulatory inputs. Glucose elicits rapid release through an adenosine triphosphate-sensitive K(+) channel (KATP channel)-dependent mechanism, which is gradually augmented KATP channel-independent manner. Biphasic GSIS thus occurs. In body, β-cells constantly exposed to signals, such as glucagon-like peptide 1 (GLP-1), parasympathetic inputs, free fatty acid (FFA), amino acids slightly suprathreshold levels glucose, even at fasting. GLP-1 increases cellular cyclic monophosphate, stimulation activates protein kinase C, FFA, generate metabolic amplification factors. Plasma concentration rises postprandially under tonic stimulation. We hypothesize that these inputs together make responsive independently from its action channels. Robust patients with loss function mutation sulfonylurea receptor, subunit channels, compatible this hypothesis. Furthermore, pre-exposure islets activator kinase A and/or C makes channel- Ca(2+)-independent occurs islet without regulation channels vivo, priming kinase C non-glucose nutrients required. To understand physiology GSIS, comprehensive integration accumulated knowledge