Effect of Silymarin in Pdx-1 expression and the proliferation of pancreatic β-cells in a pancreatectomy model

Abstract

In type 1 Diabetes Mellitus (DM) there is a destruction of pancreatic β-cells (80-90%) at the time of detection, in DM type 2 these cells are decreased significantly. The Pdx1 transcription factor plays a central role in pancreatic development and in insulin gene expression. Previously, we have demonstrated that Silymarin recovers the normal morphology and endocrine function of damaged pancreatic tissue in alloxan induced diabetic rats. The aim of this study was to analyze the effect of Silymarin in Pdx1 gene expression and its repercussion on insulin gene expression and β-cell proliferation. 72 Wistar rats were partially pancreatectomized (60%) and divided into 12 groups. Six groups were treated daily with Silymarin (200mg/kg p.o.) for 3, 7, 14, 21, 42 and 63 day periods. Also, an unpancreatectomized control group was performed. At each time interval three animals from each group were administered BrdU 18 h before the sacrifice. Insulin and Pdx-1 gene expression were assessed by RT-PCR assay in total pancreatic RNA. β-Cell proliferation was determined by immunoperoxidase assay. In contrast to the animals that were only pancreatectomized, the Silymarin treatment induced an increase in both Pdx1 and insulin gene expression as well as β-cell proliferation in pancreatic tissue (control=2.6±0.28%; untreated=14.25±0.56%; treated=39.08±4.62%). Consequently, serum insulin levels rose (control=1.01±0.02 ng/ml; untreated=1.18±0.42 ng/ml; treated=4.58±0.58 ng/ml) and serum glucose levels decreased in these animals (control=6.2±0.01 mM; untreated=9.02±0.41 mM; treated=6.41±0.32 mM). These results suggest that Silymarin may induce the proliferation of insulin-producing cells.

Keywords: Insulin; Pancreatic regeneration; Pancreatic transcription factors; Silymarin.