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葡萄糖诱导胰岛素释放的刺激-分泌偶联。XLVI. L-谷氨酰胺作为胰岛燃料的生理作用。

The stimulus-secretion coupling of glucose-induced insulin release. XLVI. Physiological role of L-glutamine as a fuel for pancreatic islets.

作者信息

Malaisse W J, Sener A, Carpinelli A R, Anjaneyulu K, Lebrun P, Herchuelz A, Christophe J

出版信息

Mol Cell Endocrinol. 1980 Nov;20(2):171-89. doi: 10.1016/0303-7207(80)90080-5.

DOI:10.1016/0303-7207(80)90080-5
PMID:7002657
Abstract

Exogenous L-glutamine is actively metabolized in rat pancreatic islets. The rate of L-glutamine deamidation largely exceeds the rate of glutamate conversion to gamma-aminobutyrate and alpha-ketoglutarate. The latter conversion occurs in part by oxidative deamination, and in part by transamination reactions coupled with the conversion of 2-keto acids (pyruvate, oxaloacetate), themselves derived from the metabolism of glutamine, to their corresponding amino acids (alanine, aspartate). An important fraction of malate formed from alpha-ketoglutarate leaves the Krebs cycle and is converted to pyruvate, the process being apparently associated with the induction of a more reduced state in cytosolic redox couples. L-Glutamine abolishes the oxidation of endogenous nutrients is documented by the fact that the glutamine-induced increase in O2 consumption is much lower than expected from the rate of 14CO2 output from islets exposed to L-[U-14C]glutamine, L-Glutamine, although decreasing K+ conductance, fails to stimulate insulin release both in the absence and presence of D-glucose. It is proposed that L-glutamine represents a major fuel for pancreatic islets under physiological conditions.

摘要

外源性L-谷氨酰胺在大鼠胰岛中被积极代谢。L-谷氨酰胺脱酰胺的速率大大超过谷氨酸转化为γ-氨基丁酸和α-酮戊二酸的速率。后者的转化部分通过氧化脱氨发生,部分通过转氨反应与2-酮酸(丙酮酸、草酰乙酸)的转化偶联,这些2-酮酸本身源自谷氨酰胺的代谢,转化为它们相应的氨基酸(丙氨酸、天冬氨酸)。由α-酮戊二酸形成的苹果酸的一大部分离开三羧酸循环并转化为丙酮酸,该过程显然与细胞溶质氧化还原对中更还原状态的诱导有关。L-谷氨酰胺消除内源性营养物质的氧化这一点由以下事实证明:谷氨酰胺诱导的氧气消耗增加远低于暴露于L-[U-14C]谷氨酰胺的胰岛中14CO2输出速率所预期的值,L-谷氨酰胺虽然降低钾离子电导,但在不存在和存在D-葡萄糖的情况下均未能刺激胰岛素释放。有人提出,在生理条件下,L-谷氨酰胺是胰岛的主要燃料。

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