Science (American Association for the Advancement of Science), 2017-08, Vol.357 (6350), p.507-511
- Myers, Robert W.
- Guan, Hong-Ping
- Ehrhart, Juliann
- Petrov, Aleksandr
- Prahalada, Srinivasa
- Tozzo, Effie
- Yang, Xiaodong
- Kurtz, Marc M.
- Trujillo, Maria
- Trotter, Dinko Gonzalez
- 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
- Scheuch, Lisa LaFranco
- 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.
2017
Details
- Autor(en) / Beteiligte
- Myers, Robert W.
- Guan, Hong-Ping
- Ehrhart, Juliann
- Petrov, Aleksandr
- Prahalada, Srinivasa
- Tozzo, Effie
- Yang, Xiaodong
- Kurtz, Marc M.
- Trujillo, Maria
- Trotter, Dinko Gonzalez
- 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
- Scheuch, Lisa LaFranco
- 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.
- Titel
- Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy
- Ist Teil von
- Science (American Association for the Advancement of Science), 2017-08, Vol.357 (6350), p.507-511
- Ort / Verlag
- United States: American Association for the Advancement of Science
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.aah5582Titel-ID: cdi_proquest_miscellaneous_1920192680
- Format
- –
- Schlagworte
- Activation, Adenosine, Adenosine kinase, Adenosine monophosphate, Adenosine triphosphate, Allosteric properties, AMP, AMP-Activated Protein Kinases - metabolism, Animal models, Animals, ATP, Blood Glucose - drug effects, Cardiomegaly - chemically induced, Complications, Diabetes, Diabetes mellitus, Energy balance, Energy levels, Enlargement, Eukaryotes, Fasting, Glucose, Glucose - metabolism, Glycogen, Glycogen - metabolism, Heart, Heart diseases, Homeostasis, Homeostasis - drug effects, Hypertrophy, Hypoglycemia, Hypoglycemia - chemically induced, Imidazoles - adverse effects, Imidazoles - chemistry, Imidazoles - pharmacology, Insulin, Insulin - pharmacology, Kinases, Macaca mulatta, Male, Mammals, Metabolic disorders, Mice, Mice, Inbred C57BL, Monkeys, Muscle, Skeletal - drug effects, Muscle, Skeletal - metabolism, Muscles, Pathways, Pharmacology, Protein kinase, Pyridines - adverse effects, Pyridines - chemistry, Pyridines - pharmacology, Rodents, Skeletal muscle, Synthesis