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

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.

Asiatic acid alleviates metabolism disorders in ob/ob mice: mechanistic insights

“…30 Retinol (vitamin A) has been proven to be able to regulate glucose and lipid metabolism, and it is believed that the physiological functions of retinol are mainly mediated by its metabolites (retinal and retinoic acid). 31 Steroid hormone dysfunction has been proved to be linked to the development of obesity and diabetes, and elevated steroid hormone production was observed in db/db mice. 32 Taking this information together, AA treatment might alleviate metabolic disorders in ob/ob mice via regulating bile acid biosynthesis, retinol metabolism, and steroid hormone biosynthesis pathways.…”

Ectodysplasin A/Ectodysplasin A Receptor System and Their Roles in Multiple Diseases

“…Insulin resistance is defined as a reduction in the metabolic response of insulin-responsive cells to insulin or an impaired/reduced response of blood glucose levels to circulating insulin at the systemic level ( Czech, 2017 ). In the liver, insulin not only regulates glucose production and utilization, but also has a broader influence on lipid metabolism ( Chen, 2021 ). When circulating blood glucose levels are elevated, pancreatic β cells secrete insulin, which binds to hepatic insulin receptor (INSR).…”

Association between Serum Vitamin A, Blood Lipid Level and Dyslipidemia among Chinese Children and Adolescents

“…VA deficiency reduces immune capacity and leads to increased morbidity and mortality due to night blindness, corneal ulceration, keratomalacia, xerophthalmia and related ocular symptoms [ 46 ]. It also increased mortality due to measles, diarrhea and respiratory diseases [ 42 , 47 , 48 , 49 , 50 , 51 , 52 ]. Therefore, more attention to the problem of VA deficiency in children and adolescents should be paid.…”