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

被引:40
作者
Komatsu, M [1 ]
Yajima, H [1 ]
Yamada, S [1 ]
Kaneko, T [1 ]
Sato, Y [1 ]
Yamauchi, K [1 ]
Hashizume, K [1 ]
Aizawa, T [1 ]
机构
[1] Shinshu Univ, Sch Med, Dept Aging Med & Geriatr, Matsumoto, Nagano 3908621, Japan
关键词
D O I
10.2337/diabetes.48.8.1543
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive KC 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 mu mol/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 mu mol/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.
引用
收藏
页码:1543 / 1549
页数:7
相关论文
共 47 条
[1]   Glucose action 'beyond ionic events' in the pancreatic β cell [J].
Aizawa, T ;
Komatsu, M ;
Asanuma, N ;
Sato, Y ;
Sharp, GWG .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (12) :496-499
[2]   ATP-SENSITIVE K+ CHANNEL-INDEPENDENT GLUCOSE ACTION IN RAT PANCREATIC BETA-CELL [J].
AIZAWA, T ;
SATO, Y ;
ISHIHARA, F ;
TAGUCHI, N ;
KOMATSU, M ;
SUZUKI, N ;
HASHIZUME, K ;
YAMADA, T .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (03) :C622-C627
[3]   Molecular or pharmacologic perturbation of the link between glucose and lipid metabolism is without effect on glucose-stimulated insulin secretion - A re-evaluation of the long-chain acyl-CoA hypothesis [J].
Antinozzi, PA ;
Segall, L ;
Prentki, M ;
McGarry, JD ;
Newgard, CB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (26) :16146-16154
[4]   Two signaling pathways, from the upper glycolytic flux and from the mitochondria, converge to potentiate insulin release [J].
Asanuma, N ;
Aizawa, T ;
Sato, Y ;
Schermerhorn, T ;
Komatsu, M ;
Sharp, GWG ;
Hashizume, K .
ENDOCRINOLOGY, 1997, 138 (02) :751-755
[5]   ESTABLISHMENT OF 2-MERCAPTOETHANOL-DEPENDENT DIFFERENTIATED INSULIN-SECRETING CELL-LINES [J].
ASFARI, M ;
JANJIC, D ;
MEDA, P ;
LI, GD ;
HALBAN, PA ;
WOLLHEIM, CB .
ENDOCRINOLOGY, 1992, 130 (01) :167-178
[6]   GLUCOSE INDUCES CLOSURE OF SINGLE POTASSIUM CHANNELS IN ISOLATED RAT PANCREATIC BETA-CELLS [J].
ASHCROFT, FM ;
HARRISON, DE ;
ASHCROFT, SJH .
NATURE, 1984, 312 (5993) :446-448
[7]   GLUCOSE METABOLISM IN MOUSE PANCREATIC ISLETS [J].
ASHCROFT, SJ ;
HEDESKOV, CJ ;
RANDLE, PJ .
BIOCHEMICAL JOURNAL, 1970, 118 (01) :143-&
[8]   Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects [J].
Boden, G ;
Chen, XH ;
Iqbal, N .
DIABETES, 1998, 47 (10) :1609-1612
[9]  
BORTZ WM, 1963, BIOCHEM Z, V339, P77
[10]   Evidence for an anaplerotic malonyl-CoA pathway in pancreatic beta-cell nutrient signaling [J].
Brun, T ;
Roche, E ;
AssimacopoulosJeannet, F ;
Corkey, BE ;
Kim, KH ;
Prentki, M .
DIABETES, 1996, 45 (02) :190-198