The mechanisms by which fatty acids increase insulin release are not known. In this study, mouse islets were used as a model and palmitate as a reference compound to study in vitro how saturated fatty acids influence pancreatic β-cells. Palmitate (625 μM) was bound to albumin. It did not affect basal insulin release (3 mM glucose) but increased the release induced by 10–15 mM glucose. This effect was dependent on the concentration of free rather than total palmitate. It was reversible and abolished by epinephrine, diazoxide, nimodipine, or omission of extracellular Ca. Bromopalmitate and methyl palmoxirate, two inhibitors of fatty acid oxidation, were ineffective alone, and only bromopalmitate partially inhibited the effects of palmitate on insulin release. The increase in insulin release produced by palmitate could not be ascribed to a blockade of ATP-sensitive K+-channels because the fatty acid only barely decreased 86Rb efflux and did not depolarize β-cells in 3 mM glucose. The small effect on 86Rb efflux might be attributed to a slight rise in the ATP/ADP ratio. No such rise occurred when palmitate was tested in 15 mM glucose, and the fatty acid consistently accelerated 86Rb efflux under these conditions. Measurements of β-cell membrane potential (intracellular microelectrodes) and of free cytoplasmic calcium (Cai 2+) in β-cells (Fura 2 technique) showed that palmitate increases Ca2+ influx; it also caused a very small mobilization of intracellular Ca. The persistence of this stimulation of Ca2+ influx in the presence of diazoxide and high K+ suggests that palmitate might act on Ca2+ channels. The rise in Ca12+ produced by palmitate was accompanied by an increase in insulin release only if the concentration of glucose was sufficiently high. The β-cell response to palmitate thus differs from the responses to glucose and other metabolized nutrients in several respects. Saturated fatty acids appear to potentiate insulin release through an increase in Ca12+ and another, yet unidentified, fuel-dependent mechanism.
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May 01 1994
Mechanisms of the Stimulation of Insulin Release by Saturated Fatty Acids: A Study of Palmitate Effects in Mouse β-cells
Catherine Warnotte;
Catherine Warnotte
Endocrinology and Metabolism Unit, University of Louvain, Faculty of Medicine
Brussels, Belgium
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Patrick Gilon;
Patrick Gilon
Endocrinology and Metabolism Unit, University of Louvain, Faculty of Medicine
Brussels, Belgium
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Myriam Nenquin;
Myriam Nenquin
Endocrinology and Metabolism Unit, University of Louvain, Faculty of Medicine
Brussels, Belgium
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Jean-Claude Henquin
Jean-Claude Henquin
Endocrinology and Metabolism Unit, University of Louvain, Faculty of Medicine
Brussels, Belgium
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Address correspondence and reprint requests to Dr. J.C. Henquin, Unité d'Endocrinologie et Métabolisme, UCL 55.30, Avenue Hippocrate 55, B-1200 Brussels, Belgium.
Diabetes 1994;43(5):703–711
Article history
Received:
September 07 1993
Revision Received:
December 09 1993
Accepted:
December 09 1993
PubMed:
8168648
Citation
Catherine Warnotte, Patrick Gilon, Myriam Nenquin, Jean-Claude Henquin; Mechanisms of the Stimulation of Insulin Release by Saturated Fatty Acids: A Study of Palmitate Effects in Mouse β-cells. Diabetes 1 May 1994; 43 (5): 703–711. https://doi.org/10.2337/diab.43.5.703
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