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- Title
Augmentation of insulin release by glucose in the absence of extracellular Ca2+: new insights into stimulus-secretion coupling.
- Authors
Komatsu, Mitsuhisa; Schermerhorn, Thomas; Noda, Mitsuhiko; Straub, Susanne G.; Aizawa, Toru; Sharp, Geoffrey W. G.; Komatsu, M; Schermerhorn, T; Noda, M; Straub, S G; Aizawa, T; Sharp, G W
- Abstract
Glucose stimulates insulin secretion in the pancreatic beta-cell by means of a synergistic interaction between at least two signaling pathways. One, the K(ATP) channel-dependent pathway, increases the entry of Ca2+ through voltage-gated channels by closure of the K(ATP) channels and depolarization of the beta-cell membrane. The resulting increase in [Ca2+]i stimulates insulin exocytosis. The other, a K(ATP) channel-independent pathway, requires that [Ca2+]i be elevated and augments the Ca2+-stimulated release. These mechanisms are in accord with the belief that glucose-stimulated insulin secretion has an essential requirement for extracellular Ca2+ and increased [Ca2+]i. However, when protein kinases A and C are activated simultaneously, a large effect of glucose to augment insulin release can be seen in the absence of extracellular Ca2+, under conditions in which [Ca2+]i is not increased, and even when [Ca2+]i is decreased to low levels by intracellular chelation with BAPTA. In the presence or absence of Ca2+, there are similarities in the characteristics of augmentation of insulin release that suggest that only one augmentation mechanism may be involved. These similarities include time course, glucose dose-responses, augmentation by nutrients other than glucose such as alpha-ketoisocaproate (alpha-KIC), and augmentation by the fatty acids palmitate and myristate. However, augmentation in the presence and absence of Ca2+ is distinctly different in GTP dependency. Therefore, exocytosis under these two conditions appears to be triggered differently-one by Ca2+ and the other by GTP or a GTP-dependent mechanism. The augmentation pathways are likely responsible for time-dependent potentiation of secretion and for the second phase of glucose-stimulated insulin release.
- Publication
Diabetes, 1997, Vol 46, Issue 12, p1928
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diab.46.12.1928