TY - JOUR
T1 - Menaquinone-4 amplified glucose-stimulated insulin secretion in isolated mouse pancreatic islets and INS-1 rat insulinoma cells
AU - Ho, Hsin Jung
AU - Shirakawa, Hitoshi
AU - Hirahara, Keisukei
AU - Sone, Hideyuki
AU - Kamiyama, Shin
AU - Komai, Michio
N1 - Funding Information:
Funding: This work was partially supported by a Grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS) to HS (#23380070 and #17H0314) and the JSPS Core-to-Core Program A (Advanced Research Networks) entitled “Establishment of international agricultural immunology research-core for a quantum improvement in food safety”.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/4/2
Y1 - 2019/4/2
N2 - 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.
AB - 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.
KW - cAMP/Epac pathway
KW - Glucose-stimulated insulin secretion
KW - Menaquinone-4
UR - http://www.scopus.com/inward/record.url?scp=85065310018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065310018&partnerID=8YFLogxK
U2 - 10.3390/ijms20081995
DO - 10.3390/ijms20081995
M3 - Article
C2 - 31018587
AN - SCOPUS:85065310018
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 8
M1 - 1995
ER -
