Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA.
Expert Opin Ther Targets. 2022 Jan;26(1):57-67. doi: 10.1080/14728222.2022.2029410. Epub 2022 Feb 9.
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.
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.
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.
目前 1 型糖尿病（T1D）的治疗方法主要集中在胰岛素补充上，以控制胰腺β细胞丧失的影响。GDF15 是一种潜在的预防 T1D 进展的治疗方法，可能有助于遏制疾病发病率的上升。
本文讨论了 GDF15 的已知作用，GDF15 是一种具有代谢、摄食和免疫调节作用的多功能蛋白，将它们联系起来突出了未来研究的开放机会。探讨了 GDF15 在预防胰岛炎和保护胰腺β细胞免受促炎细胞因子介导的细胞应激中的作用，以及 GDF15 的药理学前景和未来研究的关键领域。
GDF15 作为一种潜在的干预措施具有很大的希望，但仍需要进一步开发。临床前研究表明疗效不佳，但这一结果可能因测定总 GDF15 而不是活性形式而受到干扰。此外，GDF15 诱导厌食和类似恶心的行为以及半衰期短，这对其应用提出了重大挑战，但系统药理学方法与时间治疗相结合可能为这种目前无法预防的疾病提供一种可能的治疗方法。
