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Publication
Chronic Activation of ?2 AMPK Induces Obesity and Reduces ß Cell Function.
Authors Yavari A, Stocker CJ, Ghaffari S, Wargent ET, Steeples V, Czibik G, Pinter K,
Bellahcene M, Woods A, Martínez de Morentin PB, Cansell C, Lam BY, Chuster A,
Petkevicius K, Nguyen-Tu MS, Martinez-Sanchez A, Pullen TJ, Oliver PL,
Stockenhuber A, Nguyen C, Lazdam M, O'Dowd JF, Harikumar P, Tóth M, Beall C,
Kyriakou T, Parnis J, Sarma D, Katritsis G, Wortmann DD, Harper AR, Brown LA,
Willows R, Gandra S, Poncio V, de Oliveira Figueiredo MJ, Qi NR, Peirson SN,
McCrimmon RJ, Gereben B, Tretter L, Feket
Submitted By Submitted Externally on 4/30/2020
Status Published
Journal Cell Metabolism
Year 2016
Date Published 5/1/2016
Volume : Pages 23 : 821 - 36
PubMed Reference 27133129
Abstract Despite significant advances in our understanding of the biology determining
systemic energy homeostasis, the treatment of obesity remains a medical
challenge. Activation of AMP-activated protein kinase (AMPK) has been proposed
as an attractive strategy for the treatment of obesity and its complications.
AMPK is a conserved, ubiquitously expressed, heterotrimeric serine/threonine
kinase whose short-term activation has multiple beneficial metabolic effects.
Whether these translate into long-term benefits for obesity and its
complications is unknown. Here, we observe that mice with chronic AMPK
activation, resulting from mutation of the AMPK ?2 subunit, exhibit ghrelin
signaling-dependent hyperphagia, obesity, and impaired pancreatic islet insulin
secretion. Humans bearing the homologous mutation manifest a congruent
phenotype. Our studies highlight that long-term AMPK activation throughout all
tissues can have adverse metabolic consequences, with implications for
pharmacological strategies seeking to chronically activate AMPK systemically to
treat metabolic disease.




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