3 years ago

Vitamin K1 Inversely Correlates with Glycemia and Insulin Resistance in Patients with Type 2 Diabetes (T2D) and Positively Regulates SIRT1/AMPK Pathway of Glucose Metabolism in Liver of T2D Mice and Hepatocytes Cultured in High Glucose

There is no previous study in the literature that has examined the relationship between circulating vitamin K1 (VK1) with glycemic status in type 2 diabetes (T2D). Moreover, scientific explanation for the beneficial role of VK1 supplementation in lowering glycemia in diabetes is yet to be determined. This study for the first time demonstrated that circulating VK1 was significantly lower in T2D patients compared to age-matched control subjects, and VK1 levels in T2D were significantly and inversely associated with fasting glucose and insulin resistance (HOMA-IR), which suggest that boosting plasma VK1 may reduce the fasting glucose and insulin resistance in T2D patients. Using high fat diet-fed T2D animal model this study further investigated the positive effect of VK1 supplementation on glucose metabolism and examined the underlying molecular mechanism. Results showed that VK1 supplementation (1, 3, 5 μg/kg BW, 8 weeks) dose dependently improved the glucose tolerance, decreased body weight gain, fasting glucose and insulin, glycated hemoglobin, HOMA-IR, and cytokine secretion (MCP-1 and IL-6), and regulated the signaling pathway of hepatic glucose metabolism (SIRT1/AMPK/PI3K/PTEN/GLUT2/GK/ G6Pase), lipid oxidation (PPARα/CPT1A), and inflammation (NF-κB) in T2D mice. Comparative signal silencing studies also depicted the role of SIRT1/AMPK in mediating the effect of VK1 on glucose metabolism, lipid oxidation, and inflammation in high glucose-treated cultured hepatocytes. In conclusion, this study demonstrates that circulating VK1 has a positive effect on lowering fasting glucose and insulin resistance in T2D via regulating SIRT1/AMPK signaling pathway.

Publisher URL: www.sciencedirect.com/science

DOI: S0955286317305387

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