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|Title:||Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice|
|Author:||Tom, Robby Zachariah|
García-Roves, Pablo M. (Pablo Miguel)
Sjögren, Rasmus J. O.
Jiang, Lake Q.
Holmström, Maria H.
Deshmukh, Atul S.
Chibalin, Alexander V.
Zierath, Juleen R.
Resistència a la insulina
Ratolins (Animals de laboratori)
Mice (Laboratory animals)
|Publisher:||American Diabetes Association|
|Abstract:||AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), which act as a metabolic sensor to regulate glucose and lipid metabolism. A mutation in the γ3 subunit (AMPKγ3(R225Q)) increases basal AMPK phosphorylation, while concomitantly reducing sensitivity to AMP. AMPKγ3(R225Q) (γ3(R225Q)) transgenic mice are protected against dietary-induced triglyceride accumulation and insulin resistance. We determined whether skeletal muscle-specific expression of AMPKγ3(R225Q) prevents metabolic abnormalities in leptin-deficient ob/ob (ob/ob-γ3(R225Q)) mice. Glycogen content was increased, triglyceride content was decreased, and diacylglycerol and ceramide content were unaltered in gastrocnemius muscle from ob/ob-γ3(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 γ3(R225Q) mice, but not in ob/ob-γ3(R225Q) mice. Acetyl-CoA carboxylase phosphorylation was increased in gastrocnemius muscle from γ3(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-γ3(R225Q) mice. In conclusion, metabolic improvements arising from muscle-specific expression of AMPKγ3(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 AMPKγ3(R225Q) mutation.|
|Note:||Reproducció del document publicat a: https://doi.org/10.2337/db13-0670|
|It is part of:||Diabetes, 2014, vol. 63, num. 5, p. 1560-1571|
|Appears in Collections:||Articles publicats en revistes (Ciències Fisiològiques)|
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