T2DM is caused by the development of insulin resistance in muscle and liver coupled with the progressive failure of beta cells in the pancreas to produce sufficient quantities of insulin to overcome the increasing resistance.
In the November 15 issue of the Journal of Clinical Investigation, a study by Charlotte Ling and colleagues from Lund University, Sweden, addresses whether the dysregulation of PGC-1 expression is due to environmental or genetic factors. The authors examined the effects of insulin on muscle PGC levels in young and old, identical and fraternal, non-diabetic twins.
The authors demonstrate that the expression levels of PGC-1alpha and PGC-1beta in muscle are increased by insulin stimulation and decreased by aging. The age-dependent decrease was found to be partially heritable and only observed in individuals with a mutation in the gene encoding PGC-1alpha. This may explain the significant variation in susceptibility of individuals to T2DM as we age. The study also demonstrated that PGC-1alpha and PGC-1beta were found to each influence different aspects of glucose metabolism, lending insights into the complex interaction between genetic and environmental influences such as age on the development of insulin resistance and T2DM.
The finding that the age-dependent decrease in expression of these key genes regulating glucose metabolism is under genetic control could provide an explanation by which an environmental trigger like aging modifies genetic susceptibility to type 2 diabetes.
In an accompanying commentary, Alan R. Shuldiner and John C. McLenithan from the University of Maryland School of Medicine discuss these results and how aging, diet, exercise, and other factors can affect our susceptibility to T2DM.
TITLE: Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins.
AUTHOR CONTACT:
Charlotte Ling
Department of Endocrinology, Lund University, Malmö, Sweden
Phone: 46-4-033-6066; Fax: 46-4-033-7042; E-mail: charlotte.ling@endo.mas.lu.se.
View the PDF of this article at: http://www.jci.org/cgi/content/full/114/10/1518
ACCOMPANYING COMMENTARY:
TITLE: Genes and pathophysiology of type 2 diabetes: more than just the Randle cycle all over again.
AUTHOR CONTACT:
Alan R. Shuldiner
Division of Endocrinology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Phone: 410-706-1623; Fax: 410-706-1622; E-mail: ashuldin@medicine.umaryland.edu.
Journal
Journal of Clinical Investigation