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The Modulatory Action of Vitamin D on the Renin–Angiotensin System and the Determination of Hepatic Insulin Resistance

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Molecules 2019, 24(13), 2479; https://doi.org/10.3390/molecules24132479
Received: 18 April 2019 / Revised: 2 July 2019 / Accepted: 3 July 2019 / Published: 5 July 2019
(This article belongs to the Special Issue Bioactive Compounds for Metabolic Syndrome and Type 2 Diabetes-II)
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Abstract

Vitamin D deficiency or hypovitaminosis D is associated with increased risks of insulin resistance, type 2 diabetes mellitus (T2DM) and its related non-alcoholic fatty liver disease (NAFLD). Meanwhile, inappropriate over-activation of the renin–angiotensin system (RAS) in the liver leads to the hepatic dysfunction and increased risk of T2DM, such as abnormalities in lipid and glucose metabolism. Our previous findings have shown that calcitriol, an active metabolite of vitamin D, reduces hepatic triglyceride accumulation and glucose output in diabetic db/db mice and human hepatocellular cell HepG2 cells under insulin-resistant conditions. Notwithstanding the existence of this evidence, the protective action of vitamin D in the modulation of overexpressed RAS-induced metabolic abnormalities in the liver under insulin resistance remains to be elusive and investigated. Herein, we have reported the potential interaction between vitamin D and RAS; and its beneficial effects on the expression and function of the RAS components in HepG2 cells and primary hepatocytes under insulin-resistance states. Our study findings suggest that hormonal vitamin D (calcitriol) has modulatory action on the inappropriate upregulation of the hepatic RAS under insulin-resistant conditions. If confirmed, vitamin D supplementation might provide a nutraceutical potential as a cost-effective approach for the management of hepatic metabolic dysfunction as observed in T2DM and related NAFLD. View Full-Text
Keywords: AT1 receptor calcitriol; HepG2 cells; liver; obesity; pancreas; type 2 diabetes AT1 receptor calcitriol; HepG2 cells; liver; obesity; pancreas; type 2 diabetes
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Leung, P.S. The Modulatory Action of Vitamin D on the Renin–Angiotensin System and the Determination of Hepatic Insulin Resistance. Molecules 2019, 24, 2479.

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