Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

650516.pdf (995.97 KB)

Document type

Article

Version

Published version

Publication date

2014-05

Publication license

cc-by-nc-nd (c) American Diabetes Association, 2014
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/135010

Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.2337/db13-0670

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.

Subject

Metabolisme, Resistència a la insulina, Fisiologia, Leptina, Genètica, Músculs, Esquelet, Obesitat, Ratolins (Animals de laboratori)

Subject (English)

Metabolism, Insulin resistance, Physiology, Leptin, Genetics, Muscles, Skeleton, Obesity, Mice (Laboratory animals)

Citation

Collections

Articles publicats en revistes (Ciències Fisiològiques)

Citation

TOM, Robby Zachariah, et al. Effects of AMPK activation on insulin sensitivity and metabolism in leptin-deficient ob/ob mice. Diabetes. 2014. Vol. 63, num. 5, pags. 1560-1571. ISSN 0012-1797. [consulted: 16 of August of 2026]. Available at: https://hdl.handle.net/2445/135010

Export metadata

JSON - METS

Share record