Mugiya Takudzwa, Mothibe Mamosheledi, Khathi Andile, Ngubane Phikelelani, Sibiya Ntethelelo
Pharmacology Division, Faculty of Pharmacy, Rhodes University, Makhanda, South Africa.
School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
Front Pharmacol. 2024 Feb 1;15:1355171. doi: 10.3389/fphar.2024.1355171. eCollection 2024.
In light of the expected increase in the prevalence of diabetes mellitus due to an aging population, sedentary lifestyles, an increase in obesity, and unhealthy diets, there is a need to identify potential pharmacological agents that can heighten the risk of developing diabetes. Similarly, it is equally important to also identify those agents that show blood glucose-lowering properties. Amongst these agents are tyrosine kinase inhibitors used to treat certain types of cancers. Over the last two decades, there has been an increase in the use of targeted chemotherapy for cancers such as renal cell carcinoma, chronic leukaemia, and gastrointestinal stromal tumours. Small molecule tyrosine kinase inhibitors have been at the forefront of targeted chemotherapy. Studies have shown that small molecule tyrosine kinase inhibitors can alter glycaemic control and glucose metabolism, with some demonstrating hypoglycaemic activities whilst others showing hyperglycaemic properties. The mechanism by which small molecule tyrosine kinase inhibitors cause glycaemic dysregulation is not well understood, therefore, the clinical significance of these chemotherapeutic agents on glucose handling is also poorly documented. In this review, the effort is directed at mapping mechanistic insights into the effect of various small molecule tyrosine kinase inhibitors on glycaemic dysregulation envisaged to provide a deeper understanding of these chemotherapeutic agents on glucose metabolism. Small molecule tyrosine kinase inhibitors may elicit these observed glycaemic effects through preservation of β-cell function, improving insulin sensitivity and insulin secretion. These compounds bind to a spectrum of receptors and proteins implicated in glucose regulation for example, non-receptor tyrosine kinase SRC and ABL. Then receptor tyrosine kinase EGFR, PDGFR, and FGFR.
鉴于人口老龄化、久坐不动的生活方式、肥胖率上升以及不健康饮食导致糖尿病患病率预计会增加，有必要确定可能增加患糖尿病风险的潜在药物。同样，确定那些具有降血糖特性的药物也同样重要。这些药物中包括用于治疗某些类型癌症的酪氨酸激酶抑制剂。在过去二十年中，针对肾细胞癌、慢性白血病和胃肠道间质瘤等癌症的靶向化疗使用有所增加。小分子酪氨酸激酶抑制剂一直处于靶向化疗的前沿。研究表明，小分子酪氨酸激酶抑制剂可改变血糖控制和葡萄糖代谢，有些表现出降血糖活性，而另一些则表现出高血糖特性。小分子酪氨酸激酶抑制剂导致血糖失调的机制尚不清楚，因此，这些化疗药物对葡萄糖处理的临床意义也鲜有记载。在本综述中，致力于梳理各种小分子酪氨酸激酶抑制剂对血糖失调影响的机制见解，以期更深入地了解这些化疗药物对葡萄糖代谢的作用。小分子酪氨酸激酶抑制剂可能通过保留β细胞功能、提高胰岛素敏感性和胰岛素分泌来引发这些观察到的血糖效应。这些化合物与一系列参与葡萄糖调节的受体和蛋白质结合，例如非受体酪氨酸激酶SRC和ABL，以及受体酪氨酸激酶EGFR、PDGFR和FGFR。
