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Publications

Journal Article Review Epublish

PubMed: 40722684 DOI: 10.3390/biomedicines13071610

GLP-1 and Its Role in Glycogen Production: A Narrative Review.

Biomedicines 13(7)

Authors: Joseph Lotosky, Xavier Jean, Anungoo Altankhuyag, Saqib Khan, Ashley Bernotas, Alireza Sharafshah, Kenneth Blum, Alan Posner, Panayotis K Thanos

Affiliations

  • Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions, Clinical Research Institute on Addictions, Department of Pharmacology and Toxicology, Jacob School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14068, USA.
  • Department of Surgery, State University of New York at Buffalo, Buffalo, NY 14068, USA.
  • Kaleida Health Weight Management Center, Buffalo, NY 14203, USA.
  • Cellular and Molecular Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht 4144666949, Iran.
  • Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA. Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel.
  • Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA.
  • Department of Molecular Biology, Adelson School of Medicine, Ariel University, Ariel 40700, Israel.
  • Department of Exercise and Nutrition Sciences, State University of New York at Buffalo, Buffalo, NY 14068, USA.

Abstract

Glucagon-like peptide-1 (GLP-1) has emerged as a pivotal regulator in the management of glucose homeostasis, glycogen metabolism, and energy balance, positioning it as a critical therapeutic target for addressing obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists (GLP-1RAs) have shown promise for improving glycemic control and reducing weight through appetite regulation, delayed gastric emptying, and energy expenditure modulation. This narrative review explores the mechanisms of GLP-1-mediated glycogen metabolism and energy expenditure, particularly in key tissues-pancreas, liver, skeletal muscle, and adipose tissue. In the pancreas, GLP-1 enhances insulin secretion and beta-cell function. In the liver, it promotes glycogen synthesis via insulin-dependent and potential insulin-independent pathways, involving protein kinase B (AKT) and AMP-activated protein kinase (AMPK) signaling. Skeletal muscle benefits from GLP-1 through increased glucose uptake, AMPK activation, and mitochondrial function, facilitating glycogen storage. In adipose tissue, GLP-1 stimulates brown adipose tissue (BAT) thermogenesis and energy expenditure, contributing to weight loss. This increase in energy expenditure, along with enhanced glycogen metabolism, is a plausible mechanism for the weight loss observed with GLP-1RAs. Despite these advances, significant knowledge gaps remain, particularly regarding the direct hepatic effects of GLP-1, the extent to which it modulates glycogen metabolism in vivo, and its impact on thermogenesis in humans. Future research focusing on both the tissue-specific actions of GLP-1 and its systemic role in energy homeostasis and metabolic regulation will be essential for optimizing its therapeutic potential.

MeSH

Diabetes Mellitus, Glucagon-Like Peptide 1, Glycogen, Thermogenesis, Muscles, Insulin, Protein Kinases, Homeostasis, Liver, Pancreas, Weight Loss, Therapeutics, Tissues, Adipose Tissue, Diabetes Mellitus, Type 2