Медицинская библиотека · Science (New York, N.Y.) · 2017

Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy.

Myers Robert W, Guan Hong-Ping, Ehrhart Juliann, Petrov Aleksandr, Prahalada Srinivasa, Tozzo Effie, Yang Xiaodong, Kurtz Marc M, Trujillo Maria, Gonzalez Trotter Dinko, Feng Danqing, Xu Shiyao, Eiermann George, Holahan Marie A, Rubins Daniel, Conarello Stacey, Niu Xiaoda, Souza Sandra C, Miller Corin, Liu Jinqi, Lu Ku, Feng Wen, Li Ying, Painter Ronald E, Milligan James A, He Huaibing, Liu Franklin, Ogawa Aimie, Wisniewski Douglas, Rohm Rory J, Wang Liyang, Bunzel Michelle, Qian Ying, Zhu Wei, Wang Hongwu, Bennet Bindu, LaFranco Scheuch Lisa, Fernandez Guillermo E, Li Cai, Klimas Michael, Zhou Gaochao, van Heek Margaret, Biftu Tesfaye, Weber Ann, Kelley David E, Thornberry Nancy, Erion Mark D, Kemp Daniel M, Sebhat Iyassu K

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Аннотация

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.

Для цитирования: Myers Robert W, Guan Hong-Ping, Ehrhart Juliann, Petrov Aleksandr, Prahalada Srinivasa, Tozzo Effie, Yang Xiaodong, Kurtz Marc M, Trujillo Maria, Gonzalez Trotter Dinko, Feng Danqing, Xu Shiyao, Eiermann George, Holahan Marie A, Rubins Daniel, Conarello Stacey, Niu Xiaoda, Souza Sandra C, Miller Corin, Liu Jinqi, Lu Ku, Feng Wen, Li Ying, Painter Ronald E, Milligan James A, He Huaibing, Liu Franklin, Ogawa Aimie, Wisniewski Douglas, Rohm Rory J, Wang Liyang, Bunzel Michelle, Qian Ying, Zhu Wei, Wang Hongwu, Bennet Bindu, LaFranco Scheuch Lisa, Fernandez Guillermo E, Li Cai, Klimas Michael, Zhou Gaochao, van Heek Margaret, Biftu Tesfaye, Weber Ann, Kelley David E, Thornberry Nancy, Erion Mark D, Kemp Daniel M, Sebhat Iyassu K. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy.. Science (New York, N.Y.). 2017. DOI: 10.1126/science.aah5582.

Предметные рубрики MeSH

AMP-Activated Protein Kinases Animals Benzimidazoles Blood Glucose Cardiomegaly Fasting Glucose Glycogen Homeostasis Hypoglycemia Imidazoles Insulin Macaca mulatta Male Mice Mice, Inbred C57BL Muscle, Skeletal Pyridines

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