Accepted Preprint (first posted online 4 August 2016)

    AMPK-dependent regulation of GLP-1 expression in L-like cells

    1. Geyang Xu
    1. S Jiang, Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
    2. H Zhai , Endoscopy Center, Jinan University First Affiliated Hospital, Guangzhou, China
    3. D Li, Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
    4. J Huang, Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
    5. H Zhang, Department of Physiology, School of Medicine, Jinan University, Guangzhou, China
    6. Z Li, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
    7. W Zhang, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China
    8. G Xu, Department of Physiology,School of Medicine, Jinan University, Guangzhou, 510632, China
    1. Correspondence: Geyang Xu, Email: xugeyangliang{at}163.com

    Abstract

    This study examined whether AMPK, an evolutionarily conserved sensor of cellular energy status, determines the production of glucagon-like peptide (GLP-1). A negative relation existed between phosphorylation of AMPKα and the expression and secretion of GLP-1 during changes in energy status in STC-1 cells, an L like cell line. High concentration of glucose (25mmol/l) decreased AMPKα phosphorylation while stimulated the expression and secretion of GLP-1 relative to 5.6mmol/l glucose. Serum starvation up-regulated AMPKα phosphorylation, while significantly reduced GLP-1 production. Stimulation of AMPK phosphorylation by AICAR, as well as overexpression of wild-type AMPKα1, constitutively active AMPKα1 plasmids or AMPKα1 lentivirus particles suppressed proglucagon mRNA and protein contents in STC-1 cells. Inactivation of AMPK by Compound C, AMPKα1 siRNA or kinase inactive AMPKα1 mutant increased the expression and secretion of GLP-1. Our results suggest that AMPKα1 may link energy supply with the production of GLP-1 in L like cells.

    • Received 23 May 2016
    • Revision received 17 July 2016
    • Accepted 4 August 2016
    • Accepted Preprint first posted online on 4 August 2016