Unraveling the Gordian knot of insulin resistance in type 2 diabetes mellitus

IF 0.4 Q4 MEDICINE, RESEARCH & EXPERIMENTAL
R. Weijers
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Abstract

β-cells play an important role in unraveling the Gordian knot of insulin resistance in type 2 diabetes. Firstly, a key feature of the etiology of type 2 diabetes, which appears in the prediabetic phase, is a reduction in the unsaturation index (number of cis carbon-carbon double bonds per 100 acyl chains of membrane phospholipids) compared to healthy controls, which leads to a lower rate of transmembrane glucose transport, and consequently causes reduced glucose effectiveness. Thus, the amount of glucose entering the β-cell via glucose transporter-2 reduces insulin production, leading to reduced insulin sensitivity. Secondly, after synthesis of monomer insulin, six monomer insulin molecules can join together in the presence of zinc ions. The mature hexamers are packed inside mature intracellular vesicles that are transported to the β-cell plasma membrane. Fusion of the intracellular vesicle membrane with the β-cell plasma membrane creates a fusion pore that allows expulsion of monomer insulin molecules into the blood circulation. The large dimensions of the monomer insulin molecule (30 Å wide and 35 Å high) require substantial flexibility of the vesicle membrane and the β-cell plasma membrane. Reduction in the unsaturation indexes leads to a lower rate of insulin transport into the blood circulation, which results in a further decrease in insulin sensitivity. That brings us to a crucial point. The conceit behind the term “insulin resistance” is wrong. It suggests that cells do not respond well to insulin, but the fact is that this term ignores the essential reduction, compared to the plasma glucose concentration, in the amount of glucose entering the β-cell via glucose transporter-2, resulting in reduced insulin production. We now know that an increase in glucose effectiveness, powered by an increased unsaturation index, reframes fundamentally the mechanisms that participate in the glucose homeostasis during type 2 diabetes mellitus.
解开2型糖尿病胰岛素抵抗的难题
β-细胞在解开2型糖尿病胰岛素抵抗的难题中起着重要作用。首先,出现在糖尿病前期的2型糖尿病病因学的一个关键特征是,与健康对照组相比,不饱和指数(膜磷脂每100个酰基链的顺式碳-碳双键的数量)降低,这导致跨膜葡萄糖转运率降低,从而导致葡萄糖有效性降低。因此,通过葡萄糖转运蛋白-2进入β细胞的葡萄糖量减少了胰岛素的产生,导致胰岛素敏感性降低。其次,单体胰岛素合成后,六个单体胰岛素分子可以在锌离子存在下结合在一起。成熟的六聚体被包裹在成熟的细胞内囊泡中,这些囊泡被运送到β细胞质膜。细胞内囊泡膜与β细胞质膜的融合产生了一个融合孔,允许单体胰岛素分子进入血液循环。胰岛素单体分子的大尺寸(30 Å宽,35 Å高)要求囊泡膜和β细胞质膜具有相当大的灵活性。不饱和指数的降低导致胰岛素进入血液循环的速率降低,从而导致胰岛素敏感性进一步降低。这就引出了一个关键问题。“胰岛素抵抗”一词背后的自负是错误的。这表明细胞对胰岛素反应不佳,但事实是,这个术语忽略了与血浆葡萄糖浓度相比,通过葡萄糖转运体-2进入β-细胞的葡萄糖量的减少,导致胰岛素产生减少。我们现在知道,葡萄糖有效性的增加,由不饱和指数的增加所驱动,从根本上重新构建了参与2型糖尿病期间葡萄糖稳态的机制。
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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来源期刊
AIMS Medical Science
AIMS Medical Science MEDICINE, RESEARCH & EXPERIMENTAL-
自引率
14.30%
发文量
20
审稿时长
12 weeks
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