Details

Autor(en) / Beteiligte

• Shuldiner, Alan R
• McLenithan, John C

Titel

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

Ist Teil von

• The Journal of clinical investigation, 2004-11, Vol.114 (10), p.1414-1417

Ort / Verlag

United States: American Society for Clinical Investigation

Erscheinungsjahr

2004

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 beta cells. 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-1beta mRNA levels decrease with age in individuals with a genetic variant in PGC-1alpha, and these decreases correlate with alterations in whole-body glucose and fatty acid oxidation. These findings provide insights into how aging modifies genetic susceptibility to alterations in oxidative phosphorylation and T2DM.