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The Interactions of Insulin and Vitamin A Signaling Systems for the Regulation of Hepatic Glucose and Lipid Metabolism

Cells. 2021 Aug 21;10(8):2160. doi: 10.3390/cells10082160.

Abstract

The pandemics of obesity and type 2 diabetes have become a concern of public health. Nutrition plays a key role in these concerns. Insulin as an anabolic hormonal was discovered exactly 100 years ago due to its activity in controlling blood glucose level. Vitamin A (VA), a lipophilic micronutrient, has been shown to regulate glucose and fat metabolism. VA's physiological roles are mainly mediated by its metabolite, retinoic acid (RA), which activates retinoic acid receptors (RARs) and retinoid X receptors (RXRs), which are two transcription factors. The VA status and activations of RARs and RXRs by RA and synthetic agonists have shown to affect the glucose and lipid metabolism in animal models. Both insulin and RA signaling systems regulate the expression levels of genes involved in the regulation of hepatic glucose and lipid metabolism. Interactions of insulin and RA signaling systems have been observed. This review is aimed at summarizing the history of diabetes, insulin and VA signaling systems; the effects of VA status and activation of RARs and RXRs on metabolism and RAR and RXR phosphorylation; and possible interactions of insulin and RA in the regulation of hepatic genes for glucose and lipid metabolism. In addition, some future research perspectives for understanding of nutrient and hormone interactions are provided.

Keywords: diabetes; glucose; insulin; lipogenesis; primary hepatocytes; retinoic acid receptor; retinoid X receptor; vitamin A.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Glucose / metabolism*
  • Humans
  • Insulin / metabolism*
  • Lipid Metabolism / physiology*
  • Liver / metabolism*
  • Receptors, Retinoic Acid / metabolism
  • Retinoid X Receptors / metabolism
  • Signal Transduction / physiology
  • Vitamin A / metabolism*

Substances

  • Insulin
  • Receptors, Retinoic Acid
  • Retinoid X Receptors
  • Vitamin A
  • Glucose