Exendin-4, a glucagon-like peptide-1 receptor agonist, alleviates muscular dysfunction and wasting in a streptozotocin-induced diabetic mouse model compared to metformin

Tissue Cell. 2024 Aug:89:102479. doi: 10.1016/j.tice.2024.102479. Epub 2024 Jul 15.

Abstract

Diabetic muscular atrophy is becoming a fast-growing problem worldwide, including sarcopenia, which is associated with substantial mortality and morbidity risk. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been marketed and suggested to exert protective effects on not only glycemic control but also diabetic complications in diabetic patients. In this study, we investigated the therapeutic use of GLP-1RAs exendin-4, compared to antidiabetic drug metformin, for the intervention of muscular dysfunction during diabetic conditions using a streptozotocin (STZ)-induced diabetic mouse model. The results showed that both exendin-4 and metformin could effectively alleviate hyperglycemia in diabetic mice, and also counteract diabetes-induced muscle weight loss, weaker grip, and changes in muscle fiber cross-sectional area distribution. Unexpectedly, exendin-4, but not metformin, enhanced the increased kidney weight and histological change in diabetic mice. Taken together, these findings suggest that both exendin-4 and metformin could effectively improve the diabetic hyperglycemia and muscular dysfunction; but exendin-4 may aggravate the nephropathy in STZ-induced diabetic mice.

Keywords: Diabetic muscular atrophy; Diabetic nephropathy; Exentin-4; Glucagon-like peptide-1 receptor agonist; Metformin.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / complications
  • Diabetes Mellitus, Experimental* / drug therapy
  • Diabetes Mellitus, Experimental* / pathology
  • Disease Models, Animal
  • Exenatide* / pharmacology
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Glucagon-Like Peptide-1 Receptor* / metabolism
  • Hypoglycemic Agents / pharmacology
  • Male
  • Metformin* / pharmacology
  • Mice
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / drug therapy
  • Muscular Atrophy / etiology
  • Muscular Atrophy / pathology
  • Peptides / pharmacology
  • Streptozocin
  • Venoms / pharmacology

Substances

  • Exenatide
  • Metformin
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Streptozocin
  • Peptides
  • Venoms
  • Glucagon-Like Peptide-1 Receptor Agonists