INTERPLAY OF GLUCOSE-STIMULATED CA2+ SEQUESTRATION AND ACETYLCHOLINE-INDUCED CA2+ RELEASE AT THE ENDOPLASMIC-RETICULUM IN RAT PANCREATIC BETA-CELLS

被引:23
作者
HAMAKAWA, N [1 ]
YADA, T [1 ]
机构
[1] KAGOSHIMA UNIV,SCH MED,DEPT PHYSIOL,KAGOSHIMA 890,JAPAN
关键词
D O I
10.1016/0143-4160(95)90099-3
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
It is known that the stimulation with high glucose initially decreases as well as subsequently increases the cytosolic free Ca2+ concentration ([Ca2+](i)) in pancreatic beta-cells. In the present study, we aimed at exploring the ionic mechanism and physiological role of the glucose-induced decrease in [Ca2+](i) by measuring [Ca2+](i) in single pancreatic beta-cells from normal rats. The glucose-induced decrease in [Ca2+](i) in beta-cells was completely inhibited by thapsigargin (Tg), a specific inhibitor of the endoplasmic reticulum (ER) Ca2+ pump (Ca2+-ATPase). On the other hand, neither a Ca2+-free nor a low-Na+ condition significantly altered the glucose-induced decrease in [Ca2+](i). At basal glucose concentrations (1-4.5 mM), an insulin secretagogue acetylcholine (ACh) evoked a rather transient increase in [Ca2+](i) in the presence and absence of extracellular Ca2+. A rise in glucose concentration from 1 to 4.5 mM produced a sustained decrease in [Ca2+](i) and concomitantly augmented the ACh-evoked increase in [Ca2+](i). The resting [Ca2+](i) level determined by glucose was tightly and reciprocally correlated with the peak of the [Ca2+](i) response to ACh. Successive ACh pulses elicited repeated [Ca2+](i) responses, which were progressively inhibited by Tg, suggesting that Ca2+ released by ACh was taken up by the ER Ca2+ pump and thus cycled. The results demonstrate that glucose decreases [Ca2+](i) in pancreatic beta-cells mainly by activating the Ca2+ pump in ER from which ACh mobilizes Ca2+ Furthermore, the glucose-stimulated sequestration of Ca2+ by ER results in an augmented [Ca2+](i) response to ACh, providing a mechanistic basis for the glucose-dependent action of ACh to initiate insulin secretion.
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页码:21 / 31
页数:11
相关论文
共 39 条
[1]   EXOCYTOSIS ELICITED BY ACTION-POTENTIALS AND VOLTAGE-CLAMP CALCIUM CURRENTS IN INDIVIDUAL MOUSE PANCREATIC B-CELLS [J].
AMMALA, C ;
ELIASSON, L ;
BOKVIST, K ;
LARSSON, O ;
ASHCROFT, FM ;
RORSMAN, P .
JOURNAL OF PHYSIOLOGY-LONDON, 1993, 472 :665-688
[2]   DIAZOXIDE UNMASKS GLUCOSE INHIBITION OF INSULIN RELEASE BY COUNTERACTING ENTRY OF CA-2+ [J].
BERGSTEN, P ;
GYLFE, E ;
WESSLEN, N ;
HELLMAN, B .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (04) :E422-E427
[3]   MECHANISMS OF ACTIVATED CA2+ ENTRY IN THE RAT PANCREATOMA CELL-LINE, AR4-2J [J].
BIRD, GS ;
TAKEMURA, H ;
THASTRUP, O ;
PUTNEY, JW ;
MENNITI, FS .
CELL CALCIUM, 1992, 13 (01) :49-58
[4]  
BLONDEL O, 1993, J BIOL CHEM, V268, P11356
[5]   INSULIN RELEASE, CGMP, CAMP, AND MEMBRANE-POTENTIAL IN ACETYLCHOLINE-STIMULATED ISLETS [J].
GAGERMAN, E ;
IDAHL, LA ;
MEISSNER, HP ;
TALJEDAL, IB .
AMERICAN JOURNAL OF PHYSIOLOGY, 1978, 235 (05) :E493-E500
[6]  
GILON P, 1992, J BIOL CHEM, V267, P20713
[7]   ACTIVATION OF MUSCARINIC RECEPTORS INCREASES THE CONCENTRATION OF FREE NA+ IN MOUSE PANCREATIC B-CELLS [J].
GILON, P ;
HENQUIN, JC .
FEBS LETTERS, 1993, 315 (03) :353-356
[8]  
GOBBE P, 1989, RES COMMUN CHEM PATH, V63, P231
[9]   DUAL EFFECT OF GLUCOSE ON CYTOPLASMIC CA-2+ IN SINGLE PANCREATIC BETA-CELLS [J].
GRAPENGIESSER, E ;
GYLFE, E ;
HELLMAN, B .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 150 (01) :419-425
[10]  
GRYNKIEWICZ G, 1985, J BIOL CHEM, V260, P3440