Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive K+ channel (K(ATP) channel)-independent manner. In studying the mechanisms underlying this action, we used rat pancreatic islets and examined the effects of exogenous free fatty acids (FFAs), which are precursors of long-chain acyl-CoA (LC-CoA), on KCl-induced Ca2+-stimulated insulin release. Myristate, palmitate, and stearate augmented insulin release induced by 50 mmol/l KCl in the presence of 2.8 mmol/l glucose. Added acutely, their potency was weak compared with that of glucose-induced augmentation. The FFA-induced augmentation became much greater, however, when islets were preincubated with FFAs under stringent Ca2+-free conditions (with 1 mmol/l EGTA) before the KCl stimulation. Under these conditions, 16.7 mmol/l glucose augmented 13-fold insulin release induced by 50 mmol/l KCl, whereas palmitate or myristate (both at a free concentration of 10 micromol/l) produced 5.8- and 5.2-fold augmentations. Effects of FFAs and glucose were concentration-dependent. The temporal profiles of augmentation induced by 11.1 mmol/l glucose and 10 micromol/l palmitate were similar. Glucose and palmitate caused almost identical augmentation patterns for the initial 10 min of stimulation; subsequently, glucose augmentation was better sustained than palmitate augmentation. This suggests the existence of a longer-term glucose-specific signaling moiety that cannot be mimicked by FFAs. Our results provide direct evidence that FFAs can mimic the K(ATP) channel-independent action of glucose. Taking these results together with previous results, we conclude that glucose augments Ca2+-stimulated insulin release, at least in part, by increasing malonyl-CoA and cytosolic LC-CoA. However, one or more other glucose-specific signaling molecules are required for the full expression of augmentation.
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Abstract|
August 01 1999
Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets: free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose.
M Komatsu;
M Komatsu
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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H Yajima;
H Yajima
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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S Yamada;
S Yamada
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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T Kaneko;
T Kaneko
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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Y Sato;
Y Sato
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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K Yamauchi;
K Yamauchi
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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K Hashizume;
K Hashizume
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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T Aizawa
T Aizawa
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, Matsumoto, Japan. [email protected]
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Citation
M Komatsu, H Yajima, S Yamada, T Kaneko, Y Sato, K Yamauchi, K Hashizume, T Aizawa; Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets: free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose.. Diabetes 1 August 1999; 48 (8): 1543–1549. https://doi.org/10.2337/diabetes.48.8.1543
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