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遗传性糖尿病模型小鼠(链脲佐菌素诱导)的葡萄糖代谢存在性别差异。

Outbred Mice with Streptozotocin-Induced Diabetes Show Sex Differences in Glucose Metabolism.

机构信息

Institute of Medical Science, College of Medicine, Hallym University, 1, Hallymdaehak-gil, Chuncheon 24252, Republic of Korea.

Department of Medical Genetics, College of Medicine, Hallym University, 1, Hallymdaehak-gil, Chuncheon 24252, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Mar 8;24(6):5210. doi: 10.3390/ijms24065210.

DOI:10.3390/ijms24065210
PMID:36982285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10049093/
Abstract

Outbred mice (ICR) with different genotypes and phenotypes have been reported to be more suitable for scientific testing than inbred mice because they are more similar to humans. To investigate whether the sex and genetic background of the mice are important factors in the development of hyperglycemia, we used ICR mice and divided them into male, female, and ovariectomized female (FOVX) groups and treated them with streptozotocin (STZ) for five consecutive days to induce diabetes. Our results show that fasting blood glucose and hemoglobin A (HbA) levels were significantly higher in diabetes-induced males (M-DM) and ovariectomized diabetes-induced females (FOVX-DM) than in diabetes-induced females (F-DM) at 3 and 6 weeks after STZ treatment. Furthermore, the M-DM group showed the most severe glucose tolerance, followed by the FOVX-DM and F-DM groups, suggesting that ovariectomy affects glucose tolerance in female mice. The size of pancreatic islets in the M-DM and FOVX-DM groups was significantly different from that of the F-DM group. The M-DM and FOVX-DM groups had pancreatic beta-cell dysfunction 6 weeks after STZ treatment. Urocortin 3 and somatostatin inhibited insulin secretion in the M-DM and FOVX-DM groups. Overall, our results suggest that glucose metabolism in mice is dependent on sex and/or genetic background.

摘要

已报道称,与近交系小鼠相比,具有不同基因型和表型的远交系小鼠(ICR)更适合用于科学测试,因为它们与人类更为相似。为了研究小鼠的性别和遗传背景是否是导致高血糖的重要因素,我们使用 ICR 小鼠并将其分为雄性、雌性和去卵巢雌性(FOVX)组,并用链脲佐菌素(STZ)连续处理 5 天以诱导糖尿病。我们的结果表明,在 STZ 处理后 3 周和 6 周,糖尿病诱导的雄性(M-DM)和去卵巢糖尿病诱导的雌性(FOVX-DM)小鼠的空腹血糖和血红蛋白 A(HbA)水平明显高于糖尿病诱导的雌性(F-DM)小鼠。此外,M-DM 组的葡萄糖耐量最差,其次是 FOVX-DM 和 F-DM 组,这表明去卵巢会影响雌性小鼠的葡萄糖耐量。M-DM 和 FOVX-DM 组的胰岛大小与 F-DM 组明显不同。M-DM 和 FOVX-DM 组在 STZ 处理后 6 周出现胰岛β细胞功能障碍。Urocortin 3 和生长抑素抑制了 M-DM 和 FOVX-DM 组的胰岛素分泌。总的来说,我们的结果表明,小鼠的葡萄糖代谢依赖于性别和/或遗传背景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/44c5/10049093/e39a12dc4b66/ijms-24-05210-g006.jpg
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