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混合血统白血病基因调节胰腺β细胞中葡萄糖敏感基因表达和胰岛素分泌

Satoshi Yoshino¹, Emi Ishida¹, Kazuhiko Horiguchi¹

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan.

International journal of molecular sciences

|May 11, 2024

概括

骨髓/淋巴细胞或混合血统白血病基因 (MLL) 调节葡萄糖代谢和胰岛素分泌. 由于影响葡萄糖载体基因表达,MLL缺乏会损害葡萄糖耐受性和胰岛素释放.

科学领域:

内分泌学在内分泌学.
分子生物学分子生物学
代谢研究研究代谢研究

背景情况:

糖尿病患病率需要了解胰腺β细胞功能.
寻找调节葡萄糖有效性和胰岛素分泌的新型因素.
骨髓/淋巴细胞或混合血统白血病基因 (MLL) 以其在白血病发生和染色质调节中的作用而闻名,但其在胰腺内分泌组织中的功能尚不清楚.

研究的目的:

研究骨髓/淋巴细胞或混合血统白血病基因 (MLL) 在葡萄糖代谢和胰岛素分泌中的新型作用.
阐明MLL影响胰腺β细胞功能的分子机制.

主要方法:

在βHC-9胰腺β细胞中进行MLL倒闭.
对胰岛素分泌的评估,以应对葡萄糖负载.
对葡萄糖敏感基因表达的分析 (SLC2a1,SLC2a2).
对MLL异性淘汰赛小鼠 (MLL+/-) 的表型分析,包括葡萄糖耐受性测试和胰岛素分泌量测量.

主要成果:

在β细胞中MLL的敲击减少了胰岛素分泌和下调的葡萄糖转运基因SLC2a1和SLC2a2.
在MLL+/-小鼠中,葡萄糖耐受性受损,胰岛素分泌量减少.
在MLL+/-小鼠中,胰岛素分泌量减少与β细胞质量或胰岛素颗粒形态的变化无关.
研究结果表明,MLL调节了对葡萄糖敏感的基因表达.

结论:

骨髓/淋巴细胞或混合血统白血病基因 (MLL) 在调节葡萄糖代谢和胰岛素分泌方面发挥着新的作用.
很可能MLL与昼夜相关复合体相互作用,调节葡萄糖转运器基因表达,影响葡萄糖感应和胰岛素释放.
这些发现提供了对胰岛素分泌控制和糖尿病潜在治疗点的见解.

关键词:

在MLL中,MLL是最重要的.这就是SLC2A1A1的原因.这就是SLC2A2A2的原因.贝塔细胞贝塔细胞贝塔细胞糖尿病糖尿病患者糖尿病患者葡萄糖的反应能力.在这种情况下,胰岛素胰岛素胰岛素.

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