Multi-Tissue Acceleration of the Mitochondrial Phosphoenolpyruvate Cycle Improves Whole-Body Metabolic Health

• Published in: Cell metabolism Vol. 32; no. 5; pp. 751 - 766.e11
• Main Authors: Abulizi, Abudukadier, Cardone, Rebecca L., Stark, Romana, Lewandowski, Sophie L., Zhao, Xiaojian, Hillion, Joelle, Ma, Lingjun, Sehgal, Raghav, Alves, Tiago C., Thomas, Craig, Kung, Charles, Wang, Bei, Siebel, Stephan, Andrews, Zane B., Mason, Graeme F., Rinehart, Jesse, Merrins, Matthew J., Kibbey, Richard G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.11.2020
• Subjects: anaplerosis; Animals; cataplerosis; fatty liver; Homeostasis; human islets; Insulin - metabolism; insulin resistance; insulin secretion; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria - metabolism; mitochondrial GTP; mitochondrial PEPCK; Phosphoenolpyruvate - metabolism; phosphoenolpyruvate cycle; pyruvate kinase; Pyruvate Kinase - metabolism; Rats; Rats, Sprague-Dawley; human islets; anaplerosis; pyruvate kinase; cataplerosis; mitochondrial GTP; fatty liver; insulin secretion; mitochondrial PEPCK; phosphoenolpyruvate cycle; insulin resistance

The mitochondrial GTP (mtGTP)-dependent phosphoenolpyruvate (PEP) cycle couples mitochondrial PEPCK (PCK2) to pyruvate kinase (PK) in the liver and pancreatic islets to regulate glucose homeostasis. Here, small molecule PK activators accelerated the PEP cycle to improve islet function, as well as me...