AMPK activation is sufficient to increase skeletal muscle glucose uptake and glycogen synthesis but is not required for contraction-mediated increases in glucose metabolism

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 disp...

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Vydané v:Heliyon Ročník 8; číslo 10; s. e11091
Hlavní autori: 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.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Elsevier Ltd 01.10.2022
Elsevier
Predmet:
AMP-activated protein kinase
AMPK
diabetes
electrical treatment
glucose
glycogen
homeostasis
lactic acid
Metabolism
oxidation
Pharmacology
Skeletal muscle
therapeutics
AMPK
Pharmacology
Metabolism
Skeletal muscle
ISSN:2405-8440, 2405-8440
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Shrnutí: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. AMPK, Pharmacology,Metabolism,Skeletal muscle.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:2405-8440
2405-8440
DOI:10.1016/j.heliyon.2022.e11091