Menaquinone-4 Amplified Glucose-Stimulated Insulin Secretion in Isolated Mouse Pancreatic Islets and INS-1 Rat Insulinoma Cells
Menaquinone-4 Amplified Glucose-Stimulated Insulin Secretion in Isolated Mouse Pancreatic Islets and INS-1 Rat Insulinoma Cells
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DOI：
10.3390/ijms20081995
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发表时间：
2019-04-02
影响因子：
5.6
通讯作者：
Komai, Michio
中科院分区：
文献类型：
--
作者：
Ho, Hsin-Jung;Shirakawa, Hitoshi;Komai, Michio
维生素K2对血液凝固和骨骼代谢是不可或缺的。甲基萘醌-4 （MK-4）是维生素K2的主要同源物，在胰腺中大量存在，尽管其功能尚不清楚。同时，发现2型糖尿病患者胰岛素分泌后的-细胞功能障碍减少。为了阐明MK-4在胰腺细胞中的生理功能，我们研究了MK-4对离体小鼠胰岛和大鼠INS-1细胞的影响。葡萄糖刺激的胰岛素分泌在经MK-4处理的胰岛和INS-1细胞中显著增加。进一步阐明，MK-4提高了cAMP水平，并伴随着cAMP 2 （Epac2）依赖途径而非蛋白激酶A （PKA）依赖途径直接激活的交换蛋白的调节。发现MK-4对葡萄糖刺激胰岛素分泌的新功能，表明MK-4可能是肠促胰岛素效应的有效放大器。因此，这项研究提出了一种新的潜在的治疗胰岛素作用受损的方法。
Vitamin K2 is indispensable for blood coagulation and bone metabolism. Menaquinone-4 (MK-4) is the predominant homolog of vitamin K2, which is present in large amounts in the pancreas, although its function is unclear. Meanwhile, -cell dysfunction following insulin secretion has been found to decrease in patients with type 2 diabetes mellitus. To elucidate the physiological function of MK-4 in pancreatic -cells, we studied the effects of MK-4 treatment on isolated mouse pancreatic islets and rat INS-1 cells. Glucose-stimulated insulin secretion significantly increased in isolated islets and INS-1 cells treated with MK-4. It was further clarified that MK-4 enhanced cAMP levels, accompanied by the regulation of the exchange protein directly activated by the cAMP 2 (Epac2)-dependent pathway but not the protein kinase A (PKA)-dependent pathway. A novel function of MK-4 on glucose-stimulated insulin secretion was found, suggesting that MK-4 might act as a potent amplifier of the incretin effect. This study therefore presents a novel potential therapeutic approach for impaired insulinotropic effects.