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

4 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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