Implications of genome wide association studies for the understanding of type 2 diabetes pathophysiology

IF 5.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Biochemical pharmacology Pub Date : 2011-02-15 DOI:10.1016/j.bcp.2010.11.010
John R. Petrie , Ewan R. Pearson , Calum Sutherland
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引用次数: 63

Abstract

The rapid rise in prevalence of type 2 diabetes mellitus (T2DM) has been driven by changes in environmental factors – primarily increased caloric intake and reduced energy expenditure – resulting in reduced whole body insulin sensitivity (often termed insulin resistance). Insulin resistance has been proposed to be a major driver of progression to T2DM. However, of 38 individual susceptibility loci for T2DM recently identified by genome wide association studies, by far the majority code for proteins involved in β-cell function. In this review, we discuss the possible reasons for the paucity of insulin resistance genes and ask whether the new genetic susceptibility data should focus attention on β-cell targets in the development of therapies for T2DM.

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全基因组关联研究对了解2型糖尿病病理生理的意义
2型糖尿病(T2DM)患病率的迅速上升是由环境因素的变化驱动的——主要是热量摄入增加和能量消耗减少——导致全身胰岛素敏感性降低(通常称为胰岛素抵抗)。胰岛素抵抗被认为是T2DM进展的主要驱动因素。然而,在最近的全基因组关联研究中发现的38个个体T2DM易感位点中,到目前为止,大多数编码参与β细胞功能的蛋白质。在这篇综述中,我们讨论了胰岛素抵抗基因缺乏的可能原因,并询问新的遗传易感性数据是否应该在开发T2DM治疗方法时将重点放在β细胞靶点上。
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来源期刊
Biochemical pharmacology
Biochemical pharmacology 医学-药学
CiteScore
10.30
自引率
1.70%
发文量
420
审稿时长
17 days
期刊介绍: Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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