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硬骨鱼肝细胞对胰高血糖素样肽和胰高血糖素的代谢反应。

Metabolic response of teleost hepatocytes to glucagon-like peptide and glucagon.

作者信息

Mommsen T P, Moon T W

机构信息

Department of Biochemistry and Microbiology, University of Victoria, British Columbia, Canada.

出版信息

J Endocrinol. 1990 Jul;126(1):109-18. doi: 10.1677/joe.0.1260109.

DOI:10.1677/joe.0.1260109
PMID:2166124
Abstract

Salmon glucagon-like peptide (GLP), bovine glucagon (B-glucagon) and anglerfish glucagon (AF-glucagon), all activate glucose production in teleost hepatocytes through gluconeogenesis and glycogenolysis, but notable species differences exist in their respective effectiveness. In trout hepatocytes, gluconeogenesis appears to be the main target of hormone action. In eel cells, sampled in November, glycogenolysis was activated threefold, while gluconeogenesis was increased by 12% only. In March, glycogenolytic activation was 1.7-fold, while gluconeogenesis was increased by about 1.7-fold after exposure to B-glucagon. In brown bullhead cells, increases in glycogenolysis from seven- (GLP) to tenfold (B- and AF-glucagon) were noted, while activation of gluconeogenesis was slight. Fragments of two AF-glucagons (19-29) revealed only insignificant metabolic activity. Treatment of eel cells with B-glucagon led to large (up to 20-fold) increases in intracellular cyclic AMP (cAMP) concentrations, while exposure to GLP was accompanied by a modest (less than twofold) increase in cAMP, although metabolic effectiveness (gluconeogenesis and glycogenolysis) was similar for the two treatments. Under identical conditions, brown bullhead cellular cAMP responded poorly. Levels of cAMP peaked within 15 min following hormone application. The results imply that no simple or direct relationship exists between the amount of intracellular cAMP and the metabolic action of the glucagon family of hormones. It can further be concluded that GLPs are important regulators of hepatic metabolism, influencing identical targets as glucagon, while the mechanisms of action seem to differ.

摘要

鲑鱼胰高血糖素样肽(GLP)、牛胰高血糖素(B-胰高血糖素)和安康鱼胰高血糖素(AF-胰高血糖素)均通过糖异生和糖原分解激活硬骨鱼肝细胞中的葡萄糖生成,但它们各自的效力存在显著的物种差异。在虹鳟鱼肝细胞中,糖异生似乎是激素作用的主要靶点。在11月采集的鳗鱼细胞中,糖原分解被激活了三倍,而糖异生仅增加了12%。在3月,糖原分解激活为1.7倍,而暴露于B-胰高血糖素后糖异生增加了约1.7倍。在褐首鲶细胞中,观察到糖原分解增加了七倍(GLP)至十倍(B-和AF-胰高血糖素),而糖异生的激活则很轻微。两种AF-胰高血糖素(19-29)片段仅显示出微不足道的代谢活性。用B-胰高血糖素处理鳗鱼细胞导致细胞内环状AMP(cAMP)浓度大幅增加(高达20倍),而暴露于GLP时cAMP仅适度增加(不到两倍),尽管两种处理的代谢效力(糖异生和糖原分解)相似。在相同条件下,褐首鲶细胞的cAMP反应较差。激素应用后15分钟内cAMP水平达到峰值。结果表明,细胞内cAMP的量与胰高血糖素家族激素的代谢作用之间不存在简单或直接的关系。可以进一步得出结论,GLP是肝脏代谢的重要调节因子,影响与胰高血糖素相同的靶点,但其作用机制似乎不同。

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