Menaquinone-4 amplified glucose-stimulated insulin secretion in isolated mouse pancreatic islets and INS-1 rat insulinoma cells

Hsin Jung Ho, Hitoshi Shirakawa, Keisukei Hirahara, Hideyuki Sone, Shin Kamiyama, Michio Komai

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    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.

    Original languageEnglish
    Article number1995
    JournalInternational journal of molecular sciences
    Volume20
    Issue number8
    DOIs
    Publication statusPublished - 2019 Apr 2

    Keywords

    • Glucose-stimulated insulin secretion
    • Menaquinone-4
    • cAMP/Epac pathway

    ASJC Scopus subject areas

    • Catalysis
    • Molecular Biology
    • Spectroscopy
    • Computer Science Applications
    • Physical and Theoretical Chemistry
    • Organic Chemistry
    • Inorganic Chemistry

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