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Role of AMP-activated protein kinase in mechanism of metformin action.
It is reported that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed.
A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance.
Discovery of TBC1D1 as an Insulin-, AICAR-, and Contraction-stimulated Signaling Nexus in Mouse Skeletal Muscle*
A dissociation between AS160 protein expression and apparent AS160 PAS phosphorylation among soleus, tibialis anterior, and extensor digitorum longus muscles is discovered and is identified as the AS160 paralog TBC1D1, an obesity candidate gene regulating GLUT4 translocation in adipocytes.
Exercise, glucose transport, and insulin sensitivity.
There is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non-insulin-dependent diabetes mellitus.
Brown adipose tissue regulates glucose homeostasis and insulin sensitivity.
- K. Stanford, R. Middelbeek, L. Goodyear
- Biology, MedicineThe Journal of clinical investigation
- 2 January 2013
A previously under-appreciated role for BAT in glucose metabolism is revealed, demonstrating that BAT-derived IL-6 is required for the profound effects of BAT transplantation on glucose homeostasis and insulin sensitivity.
Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle
It is demonstrated that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle, and systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.
Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1α in skeletal muscle
It is reported here that SIRT3 responds dynamically to both exercise and nutritional signals in skeletal muscle to coordinate downstream molecular responses, and it is shown that exercise training increases Sirt3 expression as well as associated CREB phosphorylation and PGC-1α up-regulation.
Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade.
It is concluded that acute elevations of plasma FFA levels for 5 h induce skeletal muscle insulin resistance in vivo via a reduction in insulin-stimulated muscle glycogen synthesis and glucose oxidation that can be attributed to reduced glucose transport activity.
AS160 Regulates Insulin- and Contraction-stimulated Glucose Uptake in Mouse Skeletal Muscle*
- H. F. Kramer, C. Witczak, E. Taylor, N. Fujii, M. Hirshman, L. Goodyear
- BiologyJournal of Biological Chemistry
- 20 October 2006
The data suggest that AS160 regulates both insulin- and contraction-stimulated glucose metabolism in mouse skeletal muscle in vivo and that the effects of mutant AS160 on the actions of insulin and contraction are not identical.
Evidence for 5′AMP-Activated Protein Kinase Mediation of the Effect of Muscle Contraction on Glucose Transport
- Tatsuya Hayashi, M. Hirshman, Emily J Kurth, W. Winder, L. Goodyear
- Biology, MedicineDiabetes
- 1 August 1998
Data suggest that AICAR and contraction stimulate glucose transport by a similar insulin-independent signaling mechanism and are consistent with the hypothesis that AMPK is involved in exercise-stimulated glucose uptake.