GDF15: a Potential Therapeutic Target for Type 1 Diabetes
Overview
Authors
Affiliations
Introduction: Current treatment for type 1 diabetes (T1D) is centered around insulin supplementation to manage the effects of pancreatic β cell loss. GDF15 is a potential preventative therapy against T1D progression that could work to curb increasing disease incidence.
Areas Covered: This paper discusses the known actions of GDF15, a pleiotropic protein with metabolic, feeding, and immunomodulatory effects, connecting them to highlight the open opportunities for future research. The role of GDF15 in the prevention of insulitis and protection of pancreatic β cells against pro-inflammatory cytokine-mediated cellular stress are examined and the pharmacological promise of GDF15 and critical areas of future research are discussed.
Expert Opinion: GDF15 shows promise as a potential intervention but requires further development. Preclinical studies have shown poor efficacy, but this result may be confounded by the measurement of gross GDF15 instead of the active form. Additionally, the effect of GDF15 in the induction of anorexia and nausea-like behavior and short-half-life present significant challenges to its deployment, but a systems pharmacology approach paired with chronotherapy may provide a possible solution to therapy for this currently unpreventable disease.
Varhegyi V, Modos A, Trager D, Gerszi D, Horvath E, Sipos M Int J Mol Sci. 2024; 25(20).
PMID: 39456699 PMC: 11507876. DOI: 10.3390/ijms252010916.
Hoekx C, Straat M, Bizino M, van Eyk H, Lamb H, Smit J Exp Physiol. 2024; 109(8):1292-1304.
PMID: 38965822 PMC: 11291866. DOI: 10.1113/EP091815.
Growth differentiation factor 15 (GDF-15) in endocrinology.
Iglesias P, Silvestre R, Diez J Endocrine. 2023; 81(3):419-431.
PMID: 37129758 DOI: 10.1007/s12020-023-03377-9.
Overview of growth differentiation factor 15 in metabolic syndrome.
Asrih M, Wei S, Nguyen T, Yi H, Ryu D, Gariani K J Cell Mol Med. 2023; 27(9):1157-1167.
PMID: 36992609 PMC: 10148061. DOI: 10.1111/jcmm.17725.
plays a critical role in insulin secretion in INS-1 cells and human pancreatic islets.
Mohammad M, Saeed R, Mohammed A, Khalique A, Hamad M, El-Huneidi W Exp Biol Med (Maywood). 2023; 248(4):339-349.
PMID: 36740767 PMC: 10159522. DOI: 10.1177/15353702221146552.