Effects of d-Pinitol on Insulin Resistance through the PI3K/Akt Signaling Pathway in Type 2 Diabetes Mellitus Rats

Abstract

D-pinitol, a compound isolated from Pinaceae and Leguminosae plants, has been reported to possess insulin-like properties. Although the hypoglycemic activity of D-pinitol was recognized in recent years, the molecular mechanism of D-pinitol in the treatment of diabetes mellitus remains unclear. In this investigation, a model of type 2 diabetes mellitus (T2DM) with insulin resistance was established by feeding a high-fat diet (HFD) and injecting streptozocin (STZ) to Sprague-Dawley (SD) rats, targeting the exploration of more details of the mechanism in the therapy of T2DM. D-pinitol was administrated to the diabetic rats as two doses [30, 60 mg/(kg·body weight·day)]. The level of fasting blood glucose (FBG) was decreased 12.63% in the high-dosage group, and the ability of oral glucose tolerance was improved in D-pinitol-treated groups. The biochemical indices revealed that D-pinitol had a positive effect on hypoglycemic activity. Western boltting suggested that D-pinitol could promote the expression of the phosphatidylinositol-3-kinase (PI3K) p85, PI3Kp110, as well as the downstream target protein kinase B/Akt (at Ser473). Besides, D-pinitol inhibited the expression of glycogen synthesis kinase-3β (GSK-3β) protein and regulated the expression of glycogen synthesis (GS) protein and then accelerated the glycogen synthesis. Above all, D-pinitol played a positive role in regulating insulin-mediated glucose uptake in the liver through translocation and activation of the PI3K/Akt signaling pathway in T2DM rats.

Ameliorative Effects of Probiotic Lactobacillus paracasei NL41 on Insulin Sensitivity, Oxidative Stress, and Beta‐Cell Function in a Type 2 Diabetes Mellitus Rat Model

“…Previous studies have reported that a diet supplemented with L. casei strain CCFM419 increases glucose tolerance in HFD/STZ‐induced T2DM rats, L. rhamnosus GG improves glucose tolerance in STZ‐induced diabetic rats and that the impaired glucose tolerance in HFD‐fed mice is alleviated by L. fermentum strain MTCC 5689 administration, consistent with our studies. PI3K/Akt signalling pathway plays a crucial role in insulin action to regulate glucose and lipid metabolism and a long‐term HFD blunts this pathway . L. casei CCFM419 was reported to improve insulin resistance through the PI3K/Akt pathway with upregulation of PI3K and GS and downregulation of GSK‐3β mRNA expression .…”

Sugar, d ‐pinitol, volatile composition, and antioxidant activity of carob powder roasted by microwave, hot air, and combined microwave/hot air

“…Therefore, it can be used as a supplement to treat type II diabetes mellitus (Bates, Jones, & Bailey, 2000). Gao et al (2015) reported that d-pinitol played an important role in regulating insulin-mediated glucose uptake for the rats having type II diabetes mellitus. It can also be used to treat AIDS by decreasing the number of HIV in human body (Mills, Cooper, Seely, & Kanfer, 2005).…”

Oral microbe-host interactions: influence of β-glucans on gene expression of inflammatory cytokines and metabolome profile

“…Pinitol, also called D-pinitol, is a compound with multifunctional properties, among them, anti-inflammatory, cardioprotective, and anti-hyperlipidemicactions. Furthermore, pinitol is known to have properties similar to those of insulin [59–61]. …”