Metformin and growth differentiation factor 15 (GDF15) in type 2 diabetes mellitus: A hidden treasure

Type 2 diabetes mellitus (T2DM) is a chronic endocrine disorder due to the reduction of insulin sensitivity and relative deficiency of insulin secretion. Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta (TGF-β) superfamily and was initially identified as macrophage inhibitory cytokine-1 (MIC-1). GDF15 is considered a cytokine with an anti-inflammatory effect and increases insulin sensitivity, reduces body weight, and improves clinical outcomes in diabetic patients. GDF15 acts through stimulation of glial-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL), which is highly expressed in the brain stem to induce taste aversion. Metformin belongs to the group of biguanides that are derived from the plant Galega officinalis. It is interesting to note that metformin is an insulin-sensitizing agent used as a first-line therapy for T2DM that has been shown to increase the circulating level of GDF15. Thus, the present review aims to determine the critical association of the GDF15 biomarker in T2DM and how metformin agents affect it. This review illustrates that metformin activates GDF15 expression, which reduces appetite and leads to weight loss in both diabetic and nondiabetic patients. However, the present review cannot give a conclusion in this regard. Therefore, experimental, preclinical, and clinical studies are warranted to confirm the potential role of GDF15 in T2DM patients.2型糖尿病(T2DM)是一种因胰岛素敏感性降低和胰岛素分泌相对不足而引起的慢性内分泌疾病。生长分化因子15 (GDF15)属于转化生长因子-β (TGF-β)超家族，最初被鉴定为巨噬细胞抑制因子-1 (MIC)。GDF15被认为是一种具有抗炎作用、增加胰岛素敏感性、减轻体重和改善糖尿病患者临床疗效的细胞因子。GDF15通过刺激脑干高表达的胶质源性神经营养因子(GDNF)家族受体α样(GFRAL)诱导味觉厌恶。二甲双胍属于从大戟属植物中提取的双胍类化合物。二甲双胍是一种胰岛素增敏剂，用于T2DM的一线治疗，已被证明可增加GDF15的循环水平。本综述旨在确定GDF15生物标志物在T2DM中的关键作用以及二甲双胍药物是如何影响它发。综述表明，二甲双胍激活GDF15的表达，降低糖尿病和非糖尿病患者的食欲，诱导体重减轻。然而，目前的研究无法在这方面给出结论。因此，有必要进行实验、临床前和临床研究来确认GDF15在T2DM患者中的潜在作用。.