2型糖尿病的遗传基础。

4区 生物学 Q2 Biochemistry, Genetics and Molecular Biology
Advances in Genetics Pub Date : 2025-01-01 Epub Date: 2025-01-31 DOI:10.1016/bs.adgen.2024.12.001
Aditya Shah, Clancy O Bush, Rachel J Perry
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引用次数: 0

摘要

遗传是患2型糖尿病的重要风险因素,家族史使患2型糖尿病的风险增加1.5-3倍。有趣的是,当患病的父母是母亲时,这种遗传风险更高,这表明线粒体遗传学(母体遗传DNA)在糖尿病发病机制中的潜在作用,本章将探讨这一假设。虽然肥胖介导了2型糖尿病的一些遗传风险,但本章将侧重于独立于肥胖的遗传对糖尿病的影响。从机制上讲,基因变异直接或间接地促进了包括肝脏、肌肉和脂肪组织在内的关键组织的胰岛素抵抗。这种胰岛素抵抗使肝脏无法有效地抑制胰岛素对葡萄糖的产生,并在餐后状态下损害肌肉对葡萄糖的摄取。胰岛素抵抗是由基因组和环境之间复杂的相互作用驱动的,这反过来又会影响基因表达并导致代谢功能障碍的恶化。本章探讨了组织特异性遗传变化如何驱动个体器官的胰岛素抵抗,以及这些局部功能障碍如何导致2型糖尿病特征的更广泛的多器官代谢功能障碍。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic underpinnnings of type 2 diabetes.

Genetics is a significant risk factor for developing type 2 diabetes, with a family history conferring a 1.5-3-fold increased risk. Intriguingly, this heritable risk is higher when the affected parent is the mother, suggesting a potential role of mitochondrial genetics -maternally inherited DNA - in diabetes pathogenesis, a hypothesis this chapter will explore. While obesity mediates some of the genetic risk of type 2 diabetes, the chapter and will focus on genetic influences on diabetes independent of obesity. Mechanistically, genetic variants directly or indirectly contribute to insulin resistance across key tissues, including liver, muscle and adipose tissue. This insulin resistance prevents the liver from efficiently suppressing glucose production in response to insulin and impairs glucose uptake in muscle during postprandial states. Insulin resistance is driven by complex interactions between the genome and environmental, which can, in turn, influence gene expression and contribute to worsening of metabolic dysfunction. This chapter examines how tissue-specific genetic changes drive insulin resistance in individual organs and how these localized dysfunctions contribute to the broader, multi-organ metabolic dysfunction that characterize type 2 diabetes.

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来源期刊
Advances in Genetics
Advances in Genetics 生物-遗传学
CiteScore
5.70
自引率
0.00%
发文量
1
审稿时长
1 months
期刊介绍: Advances in Genetics presents an eclectic mix of articles of use to all human and molecular geneticists. They are written and edited by recognized leaders in the field and make this an essential series of books for anyone in the genetics field.
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