| Literature DB >> 28705990 |
Robert W Myers1, Hong-Ping Guan2, Juliann Ehrhart3, Aleksandr Petrov2, Srinivasa Prahalada3, Effie Tozzo2, Xiaodong Yang2, Marc M Kurtz4, Maria Trujillo5, Dinko Gonzalez Trotter6, Danqing Feng7, Shiyao Xu8, George Eiermann5, Marie A Holahan6, Daniel Rubins6, Stacey Conarello5, Xiaoda Niu4, Sandra C Souza2, Corin Miller6, Jinqi Liu2, Ku Lu2, Wen Feng4, Ying Li2, Ronald E Painter4, James A Milligan4, Huaibing He8, Franklin Liu2, Aimie Ogawa4, Douglas Wisniewski4, Rory J Rohm2, Liyang Wang4, Michelle Bunzel6, Ying Qian2, Wei Zhu2, Hongwu Wang7, Bindu Bennet3, Lisa LaFranco Scheuch3, Guillermo E Fernandez3, Cai Li5, Michael Klimas6, Gaochao Zhou4, Margaret van Heek5, Tesfaye Biftu7, Ann Weber7, David E Kelley2, Nancy Thornberry2, Mark D Erion2, Daniel M Kemp2, Iyassu K Sebhat9.
Abstract
5'-Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy homeostasis in eukaryotes. Despite three decades of investigation, the biological roles of AMPK and its potential as a drug target remain incompletely understood, largely because of a lack of optimized pharmacological tools. We developed MK-8722, a potent, direct, allosteric activator of all 12 mammalian AMPK complexes. In rodents and rhesus monkeys, MK-8722-mediated AMPK activation in skeletal muscle induced robust, durable, insulin-independent glucose uptake and glycogen synthesis, with resultant improvements in glycemia and no evidence of hypoglycemia. These effects translated across species, including diabetic rhesus monkeys, but manifested with concomitant cardiac hypertrophy and increased cardiac glycogen without apparent functional sequelae.Entities:
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Year: 2017 PMID： 28705990 DOI： 10.1126/science.aah5582
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728