Genes and pathophysiology of type 2 diabetes: more than just the Randle cycle all over again

被引：21

作者：

Shuldiner, AR

McLenithan, JC

机构：

[1] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA

[2] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2004年 / 114卷 / 10期

关键词：

D O I：

10.1172/JCI200423586

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The Randle cycle, which has been invoked to explain the reciprocal relationship between fatty acid oxidation and glucose oxidation, has long been implicated as a potential mechanism for hyperglycemia and type 2 diabetes mellitus (T2DM). Now genetic, functional genomic, and transgenic approaches have identified PPARgamma coactivators (PGC-1alpha and PGC-1beta) as key regulators of mitochondrial number and function. They regulate adaptive thermogenesis as well. as glucose and fat oxidation in muscle and fat tissue, gluconeogenesis in liver, and even glucose-regulated insulin secretion in betacells. PGC-1alpha and PGC-1beta mRNA levels and the mitochondrial genes they regulate are decreased in muscle of people with prediabetes and T2DM. A new report indicates that PGC-1alpha and PGC-lbeta mRNA levels decrease with age in individuals with a genetic variant in PGC-lalpha, and these decreases correlate with alterations in whole-body glucose and fatty acid oxidation (see the related article beginning on page 1518). These findings provide insights into how aging modifies genetic susceptibility to alterations in oxidative phosphorylation and T2DM.

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页码：1414 / 1417

页数：4

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