| First Author | Zachariah Tom R | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 5 | Pages | 1560-71 |
| PubMed ID | 24487023 | Mgi Jnum | J:229353 |
| Mgi Id | MGI:5751658 | Doi | 10.2337/db13-0670 |
| Citation | Zachariah Tom R, et al. (2014) Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. Diabetes 63(5):1560-71 |
| abstractText | AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the gamma3 subunit (AMPKgamma3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKgamma3(R225Q) (gamma3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKgamma3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-gamma3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-gamma3(R225Q) mice, whereas glucose tolerance was unaltered. Insulin-stimulated glucose uptake in extensor digitorum longus muscle during the euglycemic-hyperinsulinemic clamp was increased in lean gamma3(R225Q) mice, but not in ob/ob-gamma3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from gamma3(R225Q) mutant mice independent of adiposity. Glycogen and triglyceride content were decreased after leptin treatment (5 days) in ob/ob mice, but not in ob/ob-gamma3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKgamma3(R225Q) are insufficient to ameliorate insulin resistance and obesity in leptin-deficient mice. Central defects due to leptin deficiency may override any metabolic benefit conferred by peripheral overexpression of the AMPKgamma3(R225Q) mutation. |
