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Menaquinone-4 Amplified Glucose-Stimulated Insulin Secretion in Isolated Mouse Pancreatic Islets and INS-1 Rat Insulinoma Cells

1
Laboratory of Nutrition, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
2
International Education and Research Center for Food Agricultural Immunology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan
3
Department of Health and Nutrition, Faculty of Human Life Studies, University of Niigata Prefecture, Niigata 950-8680, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(8), 1995; https://doi.org/10.3390/ijms20081995
Received: 31 March 2019 / Revised: 15 April 2019 / Accepted: 22 April 2019 / Published: 23 April 2019
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Abstract

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, β-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 β-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. View Full-Text
Keywords: menaquinone-4; cAMP/Epac pathway; glucose-stimulated insulin secretion menaquinone-4; cAMP/Epac pathway; glucose-stimulated insulin secretion
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Ho, H.-J.; Shirakawa, H.; Hirahara, K.; Sone, H.; Kamiyama, S.; Komai, M. Menaquinone-4 Amplified Glucose-Stimulated Insulin Secretion in Isolated Mouse Pancreatic Islets and INS-1 Rat Insulinoma Cells. Int. J. Mol. Sci. 2019, 20, 1995.

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