Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology.

Diabete & metabolisme Pub Date : 1995-02-01
M J Castillo, A J Scheen, P J Lefèbvre
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Abstract

Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and may contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli but, unlike other beta-cell products, it is produced from specific a gene on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are found in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin-dependent diabetic patients. There are similarities between amylin and non beta-cell peptides such as calcitonin gene related peptides (CGRP). They may bind to the same receptor, determine similar post-receptor phenomena and qualitatively similar actions but with different degree of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactate production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions, this lactate may serve as a gluconeogenic substrate for the liver, contributing to replenish depleted glycogen stores and to increase glucose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin actions on the liver are direct or mediated by changes in circulating metabolites. A probably indirect effect of amylin in muscle is to decrease insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-stimulated insulin secretion and, in general, actions mimicking CGRP effects. Some of these actions are seen at supraphysiological concentrations. The physiopathological consequences of amylin deficiency, or excess are under active by investigated.

胰淀素/胰岛淀粉样多肽:生物化学、生理学、病理生理学。
胰淀素是一种37个氨基酸的肽,主要由胰岛细胞产生。胰淀素的聚集是淀粉样蛋白形成的部分原因。淀粉样蛋白沉积发生在细胞外和细胞内,并可能导致β细胞变性。胰淀素被包裹在β细胞颗粒中,在同样的刺激下与胰岛素共同分泌,但与其他β细胞产物不同的是,它是由12号染色体上的一个特定基因产生的。基础血浆胰淀素浓度在下午5点左右,餐后或葡萄糖后增加4倍。在胰岛素抵抗、肥胖、妊娠糖尿病和一些NIDDM患者中发现了更高的水平。在胰岛素依赖型糖尿病患者中发现低水平或无水平。胰肽与非β细胞肽如降钙素基因相关肽(CGRP)有相似之处。它们可以结合同一受体,决定相似的受体后现象和性质相似的作用,但效力程度不同。胰淀素的作用是多方面的,主要在调节燃料代谢方面发挥作用。在肌肉中,胰淀素抑制糖原合成,激活糖原分解和糖酵解(增加乳酸生成)。因此,胰淀素增加肌肉的乳酸输出并增加血浆乳酸浓度。在禁食条件下,这种乳酸可以作为肝脏的糖异生底物,有助于补充耗尽的糖原储存并增加葡萄糖的产生。在非空腹条件下,乳酸可以通过肝脏转化为甘油三酯。目前尚不清楚胰淀素对肝脏的作用是直接的还是由循环代谢物的变化介导的。胰淀素在肌肉中的间接作用可能是减少胰岛素(或葡萄糖)诱导的葡萄糖摄取,这可能有助于胰岛素抵抗。其他作用包括抑制葡萄糖刺激的胰岛素分泌,一般来说,模仿CGRP的作用。其中一些作用在超生理浓度下可见。胰淀素缺乏或过量的生理病理后果正在研究中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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