Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion.
Malonyl-CoA and long chain acyl-CoA esters as metabolic coupling factors in nutrient-induced insulin secretion.
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DOI：
10.1016/s0021-9258(18)42624-5
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发表时间：
1992-03
期刊：
影响因子：
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通讯作者：
Marc PrentkiSg;Solange VischerS;M. C. GlennonS;Romano RegazziS;Jude T. Deeneyll;Bárbara;Corkeyll
中科院分区：
文献类型：
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作者：
Marc PrentkiSg;Solange VischerS;M. C. GlennonS;Romano RegazziS;Jude T. Deeneyll;Bárbara;Corkeyll
几种方法被用来检验这一假说，该假说提出了酰基辅酶A酯在营养诱导的胰岛素释放中的作用(Prentki，M.和Matschinsky，F.M.(1987)Physiol)。Corkey，B.E.，Glennon，M.C.，Chen，K.S.，Deeney，J.T.，Matschinsky，F.M.和Prentki，M.()J.Biol。化学。21608-21612)。外源饱和长链脂肪酸显著增强葡萄糖诱导的胰岛素释放，并增加克隆β细胞系(HIT)中长链酰辅酶A酯的含量。这种分泌作用依赖于脂肪酸链的长度，发生在3-20微米(棕榈酸酯的游离浓度)范围内，并可被神经调节剂生长抑素逆转和抑制。肉碱棕榈酰转移酶I的抑制剂2-溴棕榈酸酯可抑制内源性脂肪酸的氧化，促进胰岛素的释放。只有引起分泌物的营养素或营养素的组合才会升高丙二酰辅酶A。在非刺激性燃料谷氨酰胺存在的情况下，测定了不同营养素刺激的HIT细胞的短链酰辅酶A谱。葡萄糖和亮氨酸各自在酰基-辅酶A化合物中引起类似的变化。两种促分泌剂均可使丙二酰辅酶A升高3~6倍，而琥珀酰辅酶A、游离辅酶A、乙酰辅酶A和游离辅酶A与乙酰辅酶A的比值保持不变。此外，只有当脂肪酸氧化的抑制与丙二酰辅酶A的增加相关时，长链酰辅酶A酯的总含量(线粒体+细胞质)才与各种营养物质促进的胰岛素释放负相关。结果与燃料刺激引起丙二酰辅酶A升高的概念是一致的，丙二酰辅酶A通过抑制脂肪酸氧化而增加胞内长链酰辅酶A酯。这些数据进一步支持了一个模型，在该模型中，当葡萄糖和其他营养促分泌剂刺激胰岛β细胞时，丙二酰辅酶A和长链酰辅酶A酯作为代谢偶联因子。
Several approaches were used to test the hypothesis proposing a role for acyl-CoA esters in nutrient-induced insulin release (Prentki, M., and Matschinsky, F. M. (1987) Physiol. Rev. 67, 1185-1248; Corkey, B. E., Glennon, M. C., Chen, K. S., Deeney, J. T., Matschinsky, F. M., and Prentki, M. (1989) J. Biol. Chem. 264, 21608-21612). Exogenous saturated long chain fatty acids markedly potentiated glucose-induced insulin release and elevated long chain acyl-CoA esters in the clonal beta-cell line (HIT). The secretory action depended on the fatty acid chain length, occurred in the range 3-20 microM (free concentration of palmitate), and was reversible and inhibitable by the neuromodulator somatostatin. 2-Bromopalmitate, an inhibitor of carnitine palmitoyl transferase I, suppressed the oxidation of endogenous fatty acids and promoted release of insulin. Only the nutrients or the combination of nutrients that caused secretion elevated malonyl-CoA. The short-chain acyl-CoA profile of HIT cells stimulated by various nutrients was determined in the presence of the nonstimulatory fuel glutamine. Glucose and leucine each provoked similar changes in acyl-CoA compounds. Both secretagogues elevated malonyl-CoA 3-6-fold, whereas succinyl-CoA, free CoASH, acetyl-CoA, and the free CoASH to acetyl-CoA ratio remained unaltered. Furthermore, only when inhibition of fatty acid oxidation was associated with a rise in malonyl-CoA did the total (mitochondrial plus cytoplasmic) content of long chain acyl-CoA esters correlate inversely with insulin release promoted by various nutrients. The results are consistent with the concept that fuel stimuli cause a rise in malonyl-CoA which by inhibiting fatty acid oxidation increase cytosolic long chain acyl-CoA esters. These data provide further support for a model in which malonyl-CoA and long chain acyl-CoAs esters serve as metabolic coupling factors when pancreatic beta-cells are stimulated with glucose and other nutrient secretagogues.