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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/135010
Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice
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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.
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TOM, Robby zachariah, GARCÍA-ROVES, Pablo m. (pablo miguel), SJÖGREN, Rasmus j. o., JIANG, Lake q., HOLMSTRÖM, Maria h., DESHMUKH, Atul s., VIEIRA, Elaine, CHIBALIN, Alexander v., BJÖRNHOLM, Marie, ZIERATH, Juleen r.. Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. _Diabetes_. 2014. Vol. 63, núm. 5, pàgs. 1560-1571. [consulta: 21 de gener de 2026]. ISSN: 0012-1797. [Disponible a: https://hdl.handle.net/2445/135010]