AMPK activation is sufficient to increase skeletal muscle glucose uptake and glycogen synthesis but is not required for contraction-mediated increases in glucose metabolism. Issue 10 (October 2022)

• Record Type: Journal Article
• Authors: Esquejo, Ryan M.; Albuquerque, Bina; Sher, Anna; Blatnik, Matthew; Wald, Kyle; Peloquin, Matthew; Delmore, Jake; Kindt, Erick; Li, Wenlin; Young, Jamey D.; Cameron, Kim; Miller, Russell A.
• Is Part Of: Heliyon. Volume 8:Issue 10(2022)
• Publication Date: 2022-10
• Subjects: AMPK -- Pharmacology -- Metabolism -- Skeletal muscle; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2022.e11091
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: The AMP-activated protein kinase (AMPK) is a cellular sensor of energetics and when activated in skeletal muscle during contraction can impart changes in skeletal muscle metabolism. Therapeutics that selectively activate AMPK have been developed to lower glucose levels through increased glucose disposal rates as an approach to abrogate the hyperglycemic state of diabetes; however, the metabolic fate of glucose following AMPK activation remains unclear. We have used a combination of in vivo evaluation of glucose homeostasis and ex vivo skeletal muscle incubation to systematically evaluate metabolism following pharmacological activation of AMPK with PF-739, comparing this with AMPK activation through sustained intermittent electrical stimulation of contraction. These methods to activate AMPK result in increased glucose uptake but divergent metabolism of glucose: pharmacological activation results in increased glycogen accumulation while contraction-induced glucose uptake results in increased lactate formation and glucose oxidation. These results provide additional evidence to support a role for AMPK in control of skeletal muscle metabolism and additional insight into the potential for AMPK stimulation with small molecule direct activators. Abstract : AMPK, Pharmacology, Metabolism, Skeletal muscle.