Hypoglycemic effect of D-chiro-inositol in type 2 diabetes mellitus rats through the PI3K/Akt signaling pathway

Mol Cell Endocrinol. 2016 Sep 15:433:26-34. doi: 10.1016/j.mce.2016.05.013. Epub 2016 May 20.

Abstract

In this investigation, a model of type 2 diabetes mellitus (T2DM) was used on Sprague-Dawley (SD) rats to clarify more details of the mechanism in the therapy of T2DM. D-chiro-inositol (DCI) was administrated to the diabetic rats as two doses [30, 60 mg/(kg·body weight·day)]. The biochemical indices revealed that DCI had a positive effect on hypoglycemic activity and promoted the glycogen synthesis. The rats in DCI high-dosage group had a blood glucose reduction rate of 21.5% after 5 weeks of treatment, and had insulin content in serum about 15.3 ± 2.37 mIU/L which was significantly decreased than diabetes control group. Real-time polymerase chain reaction (RT-PCR) results revealed that DCI gave a positive regulation on glycogen synthase (GS) and protein glucose transporter-4 (Glut4). Western blotting suggested that DCI could up-regulated the expression of the phosphatidylinositol-3-kinase (PI3K) p85, PI3Kp110, GS as well as the phosphorylation of protein kinase B (Akt) both in the liver and the skeletal muscle. The results also revealed that DCI enhanced the Glut4 expression on skeletal muscle. Above all, DCI played a positive role in regulating insulin-mediated glucose uptake through the PI3K/Akt signaling pathway in T2DM rats.

Keywords: D-chiro-inositol; Diabetes mellitus; Liver tissue; PI3K/Akt signaling pathway; Skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Inositol / pharmacology*
  • Insulin / metabolism
  • Insulin Resistance / physiology
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*

Substances

  • Blood Glucose
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Inositol
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt