GDF15: a potential therapeutic target for type 1 diabetes

被引:20
作者
Sarkar, Soumyadeep [1 ]
Melchior, John T. [1 ,2 ]
Henry, Hayden R. [1 ]
Syed, Farooq [3 ,4 ]
Mirmira, Raghavendra G. [5 ,6 ]
Nakayasu, Ernesto S. [1 ]
Metz, Thomas O. [1 ]
机构
[1] Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99352 USA
[2] Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA
[3] Indiana Univ Sch Med, Ctr Diabet & Metab Dis, Indianapolis, IN 46202 USA
[4] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA
[5] Univ Chicago, Kovler Diabet Ctr, Chicago, IL 60637 USA
[6] Univ Chicago, Dept Med, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
GDF15; type 1 diabetes (T1D); type 2 diabetes (T2D); insulitis; beta cells stress; ER stress; immunomodulator & chronotherapy; MACROPHAGE INHIBITORY CYTOKINE-1; DIFFERENTIATION FACTOR 15; BETA-CELL; MOLECULAR-MECHANISMS; INSULIN-RESISTANCE; RECEPTOR; GLUCOSE; WEIGHT; INDIVIDUALS; FACTOR-15;
D O I
10.1080/14728222.2022.2029410
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Current treatment for type 1 diabetes (T1D) is centered around insulin supplementation to manage the effects of pancreatic beta 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 beta 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.
引用
收藏
页码:57 / 67
页数:11
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