Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.
- K. Petersen, S. Dufour, D. Befroy, Rina Garcia, G. Shulman
- Medicine, BiologyNew England Journal of Medicine
- 12 February 2004
The hypothesis that insulin resistance in the skeletal muscle of insulin-resistant offspring of patients with type 2 diabetes is associated with dysregulation of intramyocellular fatty acid metabolism is supported, possibly because of an inherited defect in mitochondrial oxidative phosphorylation.
Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance
Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism, which supports the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.
Mitochondrial dysfunction and type 2 diabetes
Magnetic resonance spectroscopy studies in humans suggest that a defect in insulin-stimulated glucose transport in skeletal muscle is the primary metabolic abnormality in diabetes patients with type 2 diabetes, and fatty acids appear to cause this defect in glucose transport.
Lipid-induced insulin resistance: unravelling the mechanism
The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
Therapeutic approaches based on a key role for hepatic diacylglycerol activation of protein kinase Cε in triggering hepatic insulin resistance could alleviate the related epidemics of non-alcoholic fatty liver disease and type 2 diabetes.
Etiology of insulin resistance.
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Recent human studies exploring the mechanistic links between disorders of fatty acid/lipid metabolism and insulin resistance are reviewed, mainly involving the use of isotopes and/or magnetic resonance spectroscopy.
Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity.
Data suggest that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity; this may be a consequence of decreased IRS-1-associated PI 3-kinase activity.
Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents.
To further explore the nature of the mitochondrial dysfunction and insulin resistance that occur in the muscle of young, lean, normoglycemic, insulin-resistant offspring of parents with type 2…
Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction
By elucidating the cellular and molecular mechanisms responsible for insulin resistance, these studies provide potential new targets for the treatment and prevention of type 2 diabetes.