Hierarchy of control mechanisms of insulin secretion by glucose
Henquin, J.C.
Bulletin et Memoires de l'Academie Royale de Medecine de Belgique 150(3-4) 156-161; Discussion: 161-163
1995
ISSN/ISBN: 0377-8231 PMID: 8845794 Document Number: 443208
Insulin secretion from pancreatic B-cells is tightly controlled by variations in the plasma concentration of nutrients, in particular glucose. Glucose does not bind to a receptor, but must be metabolized by B-cells to influence the function of the latter. A rise of the ATP/ADP ratio in the cytoplasm closes K(+)-ATP channels in the plasma membrane. This causes depolarization with intermittent opening of Ca2+ channels and generation of a triggering signal: oscillations in the concentration of free cytoplasmic Ca2+. Glucose metabolism also generates a yet unidentified amplifying signal, that augments the efficacy of Ca2+ on the machinery releasing insulin granules. The regulation of insulin secretion may thus be achieved through variations in the amplitude of the indispensable triggering signal or of the important, but insufficient, amplifying signal.