D-Chiro-Inositol Regulates Insulin Signaling in Human Adipocytes

Abstract

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins’s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson–Golabi–Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.

New Insights into the Activities of D-Chiro-Inositol: A Narrative Review

“…In particular, DCI induces the activation of IRS without upregulating the expression of the insulin substrate. On the contrary, insulin induces both the expression and the phosphorylation of IRS, resulting in an unchanged ratio of activated IRS to total IRS [33]. As a consequence, DCI partially mimics the effect of insulin, augmenting the relative activation of IRS to a greater extent.…”

Novel Chemical and Biological Insights of Inositol Derivatives in Mediterranean Plants

“…Inositols, with particular reference to myo-inositol, D-chiro-inositol and D-pinitol, have been show to possess health promoting properties such us improving lipid profiles [71] and insulin-like effects and for these reasons may have a positive effect on patients with metabolic disorders correlatable with metabolic syndrome [72,73]. In addition, the…”

“…Inositols, with particular reference to myo-inositol, D-chiro-inositol and D-pinitol, have been show to possess health promoting properties such us improving lipid profiles [71] and insulin-like effects and for these reasons may have a positive effect on patients with metabolic disorders correlatable with metabolic syndrome [72,73]. In addition, the results of some randomized controlled studies indicate the beneficial effect of inositol supplementation on the improvement of systolic and diastolic blood pressure especially in patients with metabolic syndrome [74].…”

d-chiro-Inositol facilitates adiponectin biosynthesis and activates the AMPKα/PPARs pathway to inhibit high-fat diet-induced obesity and liver lipid deposition

“…Similarly, we did not find any cytotoxic effects on HepG2 and 3T3-L1 cells after the treatment of DCI at a concentration range of 0.1 μM-5 mM (data not shown), nor in human adipocytes. 44 Although no side effects of administration or injection of DCI in the range of 1-500 mg per kg body weight have been reported in animal studies, treatment with 500-100 mg per kg body weight of DCI (human correspondence: 2400-4800 mg day −1 ) worsens the ovarian function. 45 Strangely enough, 250 mg kg −1 day −1 DCI significantly reduced weight gain, while 500-1000 mg kg −1 DCI promoted weight gain.…”