Basu Lahari, Grieco-St-Pierre Lili, Ching Ma Enrica Angela, Stead John D H, Hanson Antonio A, Palaniyandi Jana, van Zyl Erin, Hoyeck Myriam P, McKay Kelsea S, van Allen Kyle A, Lee Hyojin, Dai Xiao-Qing, Bautista Austin, Fadzeyeva Evgenia, Mulvihill Erin E, Yauk Carole L, Mennigen Jan A, MacDonald Patrick E, Bruin Jennifer E
Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, Ontario, Canada.
Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Diabetes. 2025 Apr 1;74(4):528-543. doi: 10.2337/db24-0419.
Cancer survivors who receive cisplatin chemotherapy have an increased risk of type 2 diabetes, but the underlying mechanisms remain unclear. The aim of this study was to investigate whether cisplatin impacts β-cell health and function, thereby contributing to increased type 2 diabetes risk in cancer survivors. In vivo and in vitro cisplatin exposure dysregulated insulin secretion in male and female mice. In vitro cisplatin exposure reduced oxygen consumption, impaired β-cell exocytotic capacity, and altered expression of genes within the insulin secretion pathway in mouse islets. Understanding how chemotherapeutic drugs cause β-cell injury is critical for designing targeted interventions to reduce the risk of cancer survivors developing type 2 diabetes after treatment.
接受顺铂化疗的癌症幸存者患2型糖尿病的风险增加，但其潜在机制仍不清楚。本研究的目的是调查顺铂是否会影响β细胞的健康和功能，从而导致癌症幸存者患2型糖尿病的风险增加。体内和体外顺铂暴露会使雄性和雌性小鼠的胰岛素分泌失调。体外顺铂暴露会降低氧气消耗，损害β细胞的胞吐能力，并改变小鼠胰岛中胰岛素分泌途径内基因的表达。了解化疗药物如何导致β细胞损伤对于设计有针对性的干预措施以降低癌症幸存者治疗后患2型糖尿病的风险至关重要。
