Knocking on GDF15's door for the treatment of type 2 diabetes mellitus

Trends Endocrinol Metab. 2022 Nov;33(11):741-754. doi: 10.1016/j.tem.2022.08.004. Epub 2022 Sep 20.

Abstract

Although a large number of drugs are available for the treatment of type 2 diabetes mellitus (T2DM), many patients do not achieve adequate disease control despite adhering to medication. Recent findings indicate that the pharmacological modulation of the stress-induced cytokine growth differentiation factor 15 (GDF15) shows promise for the treatment of T2DM. GDF15 suppresses appetite and reduces inflammation, increases thermogenesis and lipid catabolism, sustains AMP-activated protein kinase (AMPK) activity, and ameliorates insulin resistance and hepatic steatosis. In addition, circulating GDF15 levels are elevated in response to several antidiabetic drugs, including metformin, with GDF15 mediating some of their effects. Here, we review the mechanistic insights into the beneficial effects of recently explored therapeutic approaches that target GDF15 for the treatment of T2DM.

Keywords: AMPK; GFRAL; NAFLD; inflammation; insulin resistance; myokine.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Growth Differentiation Factor 15 / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Lipids
  • Metformin* / pharmacology
  • Metformin* / therapeutic use

Substances

  • Growth Differentiation Factor 15
  • AMP-Activated Protein Kinases
  • Hypoglycemic Agents
  • Metformin
  • Lipids
  • GDF15 protein, human