顺铂暴露会导致雌雄小鼠的胰岛素分泌失调。

Diabetes Pub Date : 2025-04-01 DOI:10.2337/db24-0419
Lahari Basu, Lili Grieco-St-Pierre, Ma Enrica Angela Ching, John D H Stead, Antonio A Hanson, Jana Palaniyandi, Erin van Zyl, Myriam P Hoyeck, Kelsea S McKay, Kyle A van Allen, Hyojin Lee, Xiao-Qing Dai, Austin Bautista, Evgenia Fadzeyeva, Erin E Mulvihill, Carole L Yauk, Jan A Mennigen, Patrick E MacDonald, Jennifer E Bruin
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引用次数: 0

摘要

与普通人群相比,癌症幸存者患2型糖尿病的风险更高。接受顺铂(一种常见的化疗药物)治疗的患者比年龄和性别匹配的对照组更容易发生代谢综合征和2型糖尿病。令人惊讶的是,顺铂对胰岛的影响尚未见报道。我们的研究旨在确定小鼠胰岛功能是否受到全身(体内)或直接(体外)暴露于顺铂的不利影响。体内顺铂暴露导致雄性和雌性小鼠葡萄糖刺激血浆胰岛素水平的缺陷,尽管葡萄糖耐量没有差异。在体外,顺铂暴露于小鼠胰岛会以非性别特异性的方式失调胰岛素释放和减少氧气消耗。当我们将注意力转移到雄性小鼠胰岛时,顺铂在暴露后6小时就改变了与胰岛素产生、氧化应激和Bcl-2家族相关的基因表达。全基因组表达分析证实了顺铂暴露小鼠胰岛中胰岛素分泌通路内基因的明显下调。来自3名人体器官供体的数据证实,顺铂对胰岛素分泌和基因表达的有害影响在人类胰岛中重现。我们的研究结果表明,顺铂暴露会导致胰岛素分泌显著缺陷,并可能对胰岛健康产生持久影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Cisplatin Exposure Dysregulates Insulin Secretion in Male and Female Mice.

Cisplatin Exposure Dysregulates Insulin Secretion in Male and Female Mice.

Cisplatin Exposure Dysregulates Insulin Secretion in Male and Female Mice.

Cisplatin Exposure Dysregulates Insulin Secretion in Male and Female Mice.

Article highlights: 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.

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