Modulation of glucose transporter proteins by polyphenolic extract of Ichnocarpus frutescens (L.) W. T. Aiton in experimental type 2 diabetic rats

Abstract

Traditionally, in India, the decoction of Black creeper, Ichnocarpus frutescens (L.) W. T. Aiton leaves is used to treatment diabetes mellitus. However, its molecular mechanisms of antihyperglycemic effects have not been completely studied. Due to the potential antidiabetic effect of I. frutescens , we hypothesized that the polyphonic extract might add to glucose uptake through improvement in the expression of genes of the glucose transporter (GLUT) family messenger RNA (mRNA) in the liver and adipose tissues. Experimentally, diabetes mellitus was induced in Wistar rats through i.p. injection of freshly prepared solution of streptozotocin (45 mg/kg). This was done 15 minutes after the administration of nicotinamide (120 mg/kg, ip). Serum level of insulin and C-peptide were analyzed using standard methods. Glucose metabolism by the hepatocytes and adipocytes were also analyzed by quantitative RT-PCR mRNA expression levels of phosphoenolpyruvate carboxykinase 1 (PCK1), GLUT2 in the hepatocytes, and GLUT4 in the adipocytes. The hemidiaphragm were also isolated and processed to study in-vitro peripheral glucose utilization. Results of the present investigation suggest that STZ-NA induced diabetes is associated with hyperglycemia, altered levels of PCK1 and glucose transporters gene expression as well as decreased levels of insulin and C-peptide. On the other hand, the outcome of the daily oral administration of PPE to STZ-NA induced diabetic rats at different doses (150 and 300 mg/kg bodywt.) for 30 days supports our hypothesis by showing significant improvement of insulin levels, C-peptide level, downregulation of PCK1 and upregulation of GLUT (2, 4) mRNA expression levels when compared to those of diabetic rats. The administration of PPE had also increased the uptake of glucose by rat hemidiaphragm significantly. Findings from this study demonstrate that PPE enhances peripheral glucose uptake through glycogenesis pathway, mediated by upregulation of GLUT2 and GLUT4, and downregulation of PCK1. Our study suggests that the leaf of I. frutescens is a rich source of polyphenolic compounds, including those with an insulin-sensitizing function that may have the potential for treating or managing diabetes or insulin resistance.