A fatty acid-dependent step is critically important for both glucose- and non-glucose-stimulated insulin secretion

被引:128
作者
Dobbins, RL
Chester, MW
Stevenson, BE
Daniels, MB
Stein, DT
McGarry, JD
机构
[1] Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 USA
[2] Univ Texas, SW Med Ctr, Dept Biochem, Ctr Diabet Res, Dallas, TX 75235 USA
关键词
fatty acids; insulin secretion; insulin secretagogues;
D O I
10.1172/JCI1813
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Lowering of the plasma FFA level in intact fasted rats by infusion of nicotinic acid (NA) caused essentially complete ablation of insulin secretion (IS) in response to a subsequent intravenous bolus of arginine, leucine, or glibenclamide (as previously found using glucose as the beta-cell stimulus). However, in all cases, IS became supranormal when a high FFA level was maintained by co-infusion of lard oil plus heparin, Each of these secretagogues elicited little, if any, IS from the isolated, perfused "fasted" pancreas when tested simply on the background of 3 mM glucose, but all became extremely potent when 0.5 mM palmitate was also included in the medium. Similarly, IS from the perfused pancreas, in response to depolarizing concentrations of KCl, was markedly potentiated by palmitate, As was the case with intravenous glucose administration, fed animals produced an equally robust insulin response to glibenclamide regardless of whether their low basal FFA concentration was further reduced by NA. In the fasted state, arginine-induced glucagon secretion appeared to be independent of the prevailing FFA concentration, The findings establish that the essential role of circulating FFA for glucose-stimulated IS after food deprivation also applies in the case of nonglucose secretagogues, In addition, they imply that (i) a fatty acid-derived lipid moiety, which plays a pivotal role in IS, is lost from the pancreatic beta-cell during fasting; (ii) in the fasted state, the elevated level of plasma FFA compensates for this deficit; and (iii) the lipid factor acts at a late step in the insulin secretory pathway that is common to the action of a wide variety of secretagogues.
引用
收藏
页码:2370 / 2376
页数:7
相关论文
共 15 条
  • [1] CLONING OF THE BETA-CELL HIGH-AFFINITY SULFONYLUREA RECEPTOR - A REGULATOR OF INSULIN-SECRETION
    AGUILARBRYAN, L
    NICHOLS, CG
    WECHSLER, SW
    CLEMENT, JP
    BOYD, AE
    GONZALEZ, G
    HERRERASOSA, H
    NGUY, K
    BRYAN, J
    NELSON, DA
    [J]. SCIENCE, 1995, 268 (5209) : 423 - 426
  • [2] ROLE OF PLASMA FREE FATTY-ACIDS IN CONTROL OF INSULIN-SECRETION IN MAN
    BALASSE, EO
    OOMS, HA
    [J]. DIABETOLOGIA, 1973, 9 (02) : 145 - 151
  • [3] MORE DIRECT EVIDENCE FOR A MALONYL-COA-CARNITINE PALMITOYLTRANSFERASE-I INTERACTION AS A KEY EVENT IN PANCREATIC BETA-CELL SIGNALING
    CHEN, SY
    OGAWA, A
    OHNEDA, M
    UNGER, RH
    FOSTER, DW
    MCGARRY, JD
    [J]. DIABETES, 1994, 43 (07) : 878 - 883
  • [4] STIMULATION OF INSULIN-SECRETION BY LONG-CHAIN FREE FATTY-ACIDS - DIRECT PANCREATIC EFFECT
    CRESPIN, SR
    GREENOUGH, WB
    STEINBERG, D
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1973, 52 (08) : 1979 - 1984
  • [5] DOBBINS R, 1997, DIABETES S1, V46, pA50
  • [6] GREENOUGH WB, 1967, LANCET, V2, P1334
  • [7] INSULIN RELEASE IN RATS 1 AND 5 DAYS AFTER HYPOPHYSECTOMY
    HEINZE, E
    KLEINERT, W
    VOIGT, KH
    [J]. HORMONE RESEARCH, 1981, 14 (04) : 243 - 249
  • [8] Augmentation of insulin release by glucose in the absence of extracellular Ca2+ - New insights into stimulus-secretion coupling
    Komatsu, M
    Schermerhorn, T
    Noda, M
    Straub, SG
    Aizawa, T
    Sharp, GWG
    [J]. DIABETES, 1997, 46 (12) : 1928 - 1938
  • [9] beta-cell function in normal rats made chronically hyperleptinemic by adenovirus-leptin gene therapy
    Koyama, K
    Chen, GX
    Wang, MY
    Lee, Y
    Shimabukuro, M
    Newgard, CB
    Unger, RH
    [J]. DIABETES, 1997, 46 (08) : 1276 - 1280
  • [10] PRENTKI M, 1992, J BIOL CHEM, V267, P5802