Vitamin D deficiency induces insulin resistance and re‐supplementation attenuates hepatic glucose output via the PI3K‐AKT‐FOXO1 mediated pathway
Mutt, Shivaprakash Jagalur; Raza, Ghulam Shere; Mäkinen, Markus J; Keinänen‐Kiukaanniemi, Sirkka; Järvelin, Marjo‐Riitta; Herzig, Karl‐Heinz (2019-12-04)
Mutt, S. J., Raza, G. S., Mäkinen, M. J., Keinänen‐Kiukaanniemi, S., Järvelin, M., Herzig, K., Vitamin D Deficiency Induces Insulin Resistance and Re‐Supplementation Attenuates Hepatic Glucose Output via the PI3K‐AKT‐FOXO1 Mediated Pathway. Mol. Nutr. Food Res. 2019, 64, 1900728. https://doi.org/10.1002/mnfr.201900728
© 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article: Mutt, S. J., Raza, G. S., Mäkinen, M. J., Keinänen‐Kiukaanniemi, S., Järvelin, M., Herzig, K., Vitamin D Deficiency Induces Insulin Resistance and Re‐Supplementation Attenuates Hepatic Glucose Output via the PI3K‐AKT‐FOXO1 Mediated Pathway. Mol. Nutr. Food Res. 2019, 64, 1900728., which has been published in final form at https://doi.org/10.1002/mnfr.201900728. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
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https://urn.fi/URN:NBN:fi-fe2020052038560
Tiivistelmä
Abstract
Background: Pandemic vitamin D deficiency is associated with insulin resistance and type 2 diabetes. Vitamin D supplementation has been reported to have improved glucose homeostasis. However, its mechanism to improve insulin sensitivity remains unclear.
Methods and results: Male C57BL/6J mice are fed with/without vitamin D control (CD) or Western (WD) diets for 15 weeks. The vitamin‐D‐deficient lean (CDVDD) and obese (WDVDD) mice are further subdivided into two groups. One group is re‐supplemented with vitamin D for 6 weeks and hepatic insulin signaling is examined. Both CD and WD mice with vitamin D deficiency developed insulin resistance. Vitamin D supplementation in CDVDD mice significantly improved insulin sensitivity, hepatic inflammation, and antioxidative capacity. The hepatic insulin signals like pAKT, pFOXO1, and pGSK3β are increased and the downstream Pepck, G6pase, and Pgc1α are reduced. Furthermore, the lipogenic genes Srebp1c, Acc, and Fasn are decreased, indicating that hepatic lipid accumulation is inhibited.
Conclusion: The results demonstrate that vitamin D deficiency induces insulin resistance. Its supplementation has significant beneficial effects on pathophysiological mechanisms in type 2 diabetes but only in lean and not in the obese phenotype. The increased subacute inflammation and insulin resistance in obesity cannot be significantly alleviated by vitamin D supplementation. This needs to be taken into consideration in the design of new clinical trials.
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