Castillo M J, Scheen A J, Lefèbvre P J
Department of Medicine, CHU Liège, Belgium.
Diabete Metab. 1995 Feb;21(1):3-25.
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.
胰淀素是一种主要由胰岛β细胞产生的37个氨基酸的肽。胰淀素的聚集部分导致淀粉样蛋白的形成。淀粉样蛋白沉积物在细胞外和细胞内均有出现，并可能导致β细胞变性。胰淀素包装在β细胞颗粒中，并在相同刺激下与胰岛素共同分泌，但与其他β细胞产物不同，它由12号染色体上的特定基因产生。基础血浆胰淀素浓度约为5 pM，餐后或葡萄糖刺激后会增加四倍。在胰岛素抵抗、肥胖、妊娠期糖尿病以及一些非胰岛素依赖型糖尿病患者中发现较高水平。在胰岛素依赖型糖尿病患者中发现水平较低或缺乏。胰淀素与非β细胞肽如降钙素基因相关肽（CGRP）之间存在相似性。它们可能与相同的受体结合，决定相似的受体后现象和定性相似的作用，但效力程度不同。胰淀素的作用是多方面的，主要作用于调节燃料代谢。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，这种乳酸可作为肝脏糖异生的底物，有助于补充耗尽的糖原储备并增加葡萄糖生成。在非禁食条件下，乳酸可被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。胰淀素在肌肉中的一个可能的间接作用是降低胰岛素（或葡萄糖）诱导的葡萄糖摄取，这可能导致胰岛素抵抗。其他作用包括抑制葡萄糖刺激的胰岛素分泌，以及一般来说模仿CGRP作用的作用。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积极研究中。
