Details

Autor(en) / Beteiligte

• Ohsaki, Yusuke
• Ho, Hsin-Jung
• Minegishi, Yoshihiko
• Ito, Asagi
• Komai, Michio
• Shirakawa, Hitoshi

Titel

Recent discoveries on the effects of vitamin K on endocrine

Ist Teil von

• Annals of nutrition and metabolism, 2023-08, Vol.79, p.217

Ort / Verlag

Basel: S. Karger AG

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Vitamin K is one of the fat-soluble vitamins and is mainly composed of vitamin K1 contained in plants and vitamin K2 (menaquinone) derived mainly from microorganisms. It has been shown that some of the ingested vitamin K is specifically converted in animal tissues to menaquinone-4 (MK-4), a type of vitamin K2. This MK-4 is known to have certain effects not found in other vitamin Ks. Vitamin K acts as a cofactor for γ-glutamylcarboxylase and is an essential cofactor involved in post-translational modification (activation) of vitamin K-dependent proteins. Since vitamin K-dependent proteins include blood coagulation factors and bone matrix proteins, vitamin K plays an important role in blood coagulation and maintenance of bone homeostasis. On the other hand, vitamin K is also present in high concentrations in several tissues other than the liver and bones. Tissues such as testis and pancreas, where the action of vitamin K is not fully understood, contains relatively higher concentration of MK-4 in the regardless of the type of vitamin K ingested, suggesting that vitamin K, especially MK-4, could possess unknown functions. We attempted to elucidate the novel function of vitamin K by analyzing the gene expression level of rat testis by the DNA microarray method. The expression level of a series of genes involved in the synthesis pathway of isoprenoid, cholesterol, and testosterone, including Cyp11a, a rate-determining enzyme to produce testosterone, were altered depending on the degree of vitamin K sufficiency. In addition, plasma and testicular testosterone levels were also significantly increased in the group with vitamin K supplemented diet compared to vitamin K deficient diet group, indicating that vitamin K could involve in androgen hormone production. In addition, an experimental system using testis Leydig cell lines also confirmed testosterone production dependent on the addition of vitamin K, suggesting that the cAMP-PKA-CREB-mediated pathway is involved in this mechanism. We also conducted a study using the islets of Langerhans cell in the mouse pancreas to elucidate the function of vitamin K in the pancreas. We have shown that vitamin K enhances glucose-stimulated insulin secretion and may be involved in glycemic homeostasis. Furthermore, in a study using β-cell lines, it was also shown that vitamin K enhances glucose-stimulated insulin secretion in a concentration-dependent manner. As part of the mechanism, we have shown that it may be mediated by the exchange protein directly activated by cAMP 2 (Epac 2) pathway following the increase in intracellular cAMP concentration. These results indicate that vitamin K may be involved in testicular androgen hormone production, and maintenance of blood glucose levels through pancreatic insulin secretion.