Regulation of Gene Expression in Downstream Signaling Molecules by Herbal Compound in Insulin Resistant Diabetic Rats

Abstract

Background: In previous studies, Sharma et al. has already isolated an anti-hyperglycemic compound from the fruit pulp of Eugenia jambolana using HPLC and other chromatographic techniques. However, the effect of antihyperglycemic compound (FIIc) on the expression of PPAR gamma, IRS-1 and IRS-2 in high sucrose diet induced type 2 diabetic rats has not been studied so far. Methods: There were exactly 24 Male Wistar rats were taken and fed on High Sucrose Diet (HSD) for the development of type 2 diabetic animal for 30 weeks. Active compound FIIc was given to group C and Pioglitazone to group D at dose of 20 mg/kg of b.w. orally for 30 weeks respectively. Blood was drawn for the estimation of plasma glucose and serum insulin at week o and at week 30 from retro orbital plexus. At the end of the study animal were sacrificed and organs including pancreas and skeletal muscles were isolated and stored at -80°C. Total RNA was isolated by using Trizol method and expression of PPAR gamma, IRS-1 and IRS-2 was quantified and compared among the study groups by Real Time PCR. Results: After treatment with FIIc for 30 weeks we found a significant reduction in post prandial blood glucose levels in group C rats compared to group B. Serum insulin was also reduced in group C rats compared to group B. In skeletal muscles the mRNA expression of PPAR γ and IRS-1 was found to be 2.48 fold and 2.56 fold increased respectively as compared to group B. Similarly the mRNA expression of IRS-2 in pancreas was found to be 2.69 folds increased as compared to group B. Conclusion: FIIc treatment for 30 weeks improves glycemic control and insulin sensitivity by increasing the mRNA expression of PPAR γ, IRS-1 and IRS-2.