Are metabolic oscillations responsible for normal oscillatory insulin secretion?

被引:169
作者
Tornheim, K [1 ]
机构
[1] BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118
关键词
D O I
10.2337/diabetes.46.9.1375
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Normal insulin secretion is oscillatory in vivo and in vitro, with a period of similar to 5-10 min. The mechanism of generating these oscillations is not yet established, but a metabolic basis seems most likely for glucose-stimulated secretion. The rationale is that I)spontaneous oscillatory operation of glycolysis is a well-established phenomenon; 2) oscillatory behavior of glycolysis involves oscillations in the ATP/ADP ratio, which can cause alternating opening and closing of ATP-sensitive K+ channels, leading to the observed oscillations in membrane potential and Ca2+ influx in pancreatic beta-cells, and may also have downstream effects on exocytosis; 3) spontaneous Ca2+ oscillations are an unlikely basis in this case, since intracellular stores are not of primary importance in the stimulus-secretion coupling, and furthermore, insulin oscillations occur under conditions when intracellular Ca2+ levels are not changing; 4) a neural basis cannot account for insulin oscillations from perifused islets and clonal beta-cells or from transplanted islets or pancreas in vivo; 5) observed oscillations in metabolite levels and fluxes further support a metabolic basis, as does the presence in beta-cells of the oscillatory isoform of phosphofructokinase (PFK-M). The fact that normal oscillatory secretion is impaired in patients with NIDDM: and in their near relatives suggests that such derangement may be involved in the development of the disease; furthermore, this probably reflects an early defect in the regulation and operation of the fuel metabolizing/sensing pathways of the pancreatic beta-cell.
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页码:1375 / 1380
页数:6
相关论文
共 79 条
  • [1] ATP-SENSITIVE K+ CHANNEL-INDEPENDENT GLUCOSE ACTION IN RAT PANCREATIC BETA-CELL
    AIZAWA, T
    SATO, Y
    ISHIHARA, F
    TAGUCHI, N
    KOMATSU, M
    SUZUKI, N
    HASHIZUME, K
    YAMADA, T
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (03): : C622 - C627
  • [2] ANDRES V, 1990, J BIOL CHEM, V265, P21441
  • [3] GLUCOSE INDUCES CLOSURE OF SINGLE POTASSIUM CHANNELS IN ISOLATED RAT PANCREATIC BETA-CELLS
    ASHCROFT, FM
    HARRISON, DE
    ASHCROFT, SJH
    [J]. NATURE, 1984, 312 (5993) : 446 - 448
  • [4] BERGSTEN P, 1994, J BIOL CHEM, V269, P8749
  • [5] SLOW AND FAST OSCILLATIONS OF CYTOPLASMIC CA2+ IN PANCREATIC-ISLETS CORRESPOND TO PULSATILE INSULIN RELEASE
    BERGSTEN, P
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1995, 268 (02): : E282 - E287
  • [6] OSCILLATORY INSULIN-SECRETION IN PERIFUSED ISOLATED RAT ISLETS
    BERGSTROM, RW
    FUJIMOTO, WY
    TELLER, DC
    DEHAEN, C
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 257 (04): : E479 - E485
  • [7] BERRIDGE MJ, 1990, J BIOL CHEM, V265, P9583
  • [8] CYTOSOLIC CALCIUM OSCILLATORS
    BERRIDGE, MJ
    GALIONE, A
    [J]. FASEB JOURNAL, 1988, 2 (15) : 3074 - 3082
  • [9] PHASE RELATIONSHIP OF GLYCOLYTIC INTERMEDIATES IN YEAST CELLS WITH OSCILLATORY METABOLIC CONTROL
    BETZ, A
    CHANCE, B
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1965, 109 (03) : 585 - &
  • [10] EFFICACY OF PULSATILE VERSUS CONTINUOUS INSULIN ADMINISTRATION ON HEPATIC GLUCOSE-PRODUCTION AND GLUCOSE-UTILIZATION IN TYPE-I DIABETIC HUMANS
    BRATUSCHMARRAIN, PR
    KOMJATI, M
    WALDHAUSL, WK
    [J]. DIABETES, 1986, 35 (08) : 922 - 926