Gymnastik- och idrottshögskolan, GIH

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The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers: potential for lactate autocrine signaling.
Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. (Åstrand laboratory, Student)
Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. (Åstrand laboratory, Student)
Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics. Department of Clinical Science, Intervention and Technology, Karolinska Institute, Sweden.ORCID iD: 0000-0003-1942-2919
Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.ORCID iD: 0000-0002-4853-6627
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2023 (English)In: American Journal of Physiology - Cell Physiology, ISSN 0363-6143, E-ISSN 1522-1563, Vol. 324, no 2, p. C477-C487Article in journal (Refereed) Published
Abstract [en]

GPR81 was first identified in adipocytes as a receptor for L-lactate, which upon binding inhibits cAMP-PKA-CREB signaling. Moreover, incubation of myotubes with lactate augments expression of GPR81 and genes and proteins involved in lactate- and energy metabolism. However, characterization of GPR81 expression and investigation of related signaling in human skeletal muscle under conditions of elevated circulating lactate levels are lacking. Muscle biopsies were obtained from healthy men and women at rest, after leg extension exercise, with or without venous infusion of sodium lactate, and 90 and 180 min after exercise (8 men and 8 women). Analyses included protein and mRNA levels of GPR81, as well as GPR81-dependent signaling molecules. GPR81 expression was 2.5-fold higher in type II glycolytic compared with type I oxidative muscle fibers, and the expression was inversely related to the percentage of type I muscle fibers. Muscle from women expressed about 25% more GPR81 protein than from men. Global PKA-activity increased by 5-8% after exercise, with no differences between trials. CREBS133 phosphorylation was reduced by 30% after exercise and remained repressed during the entire trials, with no influence of the lactate infusion. The mRNA expression of VEGF and PGC-1α were increased by 2.5 - 6-fold during recovery, and that of LDH reduced by 15% with no differences between trials for any gene at any time point. The high expression of GPR81-protein in type II fibers suggests that lactate functions as an autocrine signaling molecule in muscle; however, lactate does not appear to regulate CREB signaling during exercise.

Place, publisher, year, edition, pages
American Physiological Society , 2023. Vol. 324, no 2, p. C477-C487
Keywords [en]
CREB, HCAR1, PGC-1alpha, PKA, Resistance exercise
National Category
Sport and Fitness Sciences Physiology
Research subject
Medicine/Technology
Identifiers
URN: urn:nbn:se:gih:diva-7464DOI: 10.1152/ajpcell.00443.2022ISI: 000959663400012PubMedID: 36622074OAI: oai:DiVA.org:gih-7464DiVA, id: diva2:1725561
Conference
324(2):C477-C487
Available from: 2023-01-11 Created: 2023-01-11 Last updated: 2023-05-18

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Apro, WilliamBlackwood, Sarah JKatz, AbramMoberg, Marcus

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