Towards a better source of insulin

Author:  Rangarajan Sunil
Date:  November 2007

A team of researchers from China led by Tao Liu and Chun-You Wang have performed the differentiation of rat pancreatic ductal epithelial cells into insulin-producing cells after transfection with pancreatic and duodenal homeobox factor-1 (PDX-1) gene. The researchers have shown that the production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference.

Liu et al. transfected PDX-1 into primary pancreatic ductal epithelial cells using plasmids and then induced differentiation of the transfected cells into insulin-producing cells using selective media. Insulin production and secretion were compared between transfected and untransfected cells in media with varying glucose concentration. Conclusive evidences of increased insulin gene activation, insulin production and secretion were demonstrated among the transfected cells.

Current limitation in islet cell transplantation is at the first stage itself – in harvesting the cells. Substantial efforts have been made to differentiate embryonic stem cells, pancreatic ductal epithelial multipotent progenitor cells and bone marrow stem cells into islet cells. However, the process of cell differentiation and growth is long. Moreover, the amount of differentiated cells, and the insulin released by the cells, is not enough to meet clinical needs.

PDX-1 plays a central role in regulating pancreatic development and insulin gene transcription. Various studies have shown that transfection of PDX-1 gene confers pancreatic beta cell properties (of sensing glucose levels, producing and secreting insulin) to intestinal epithelial cells (rats) and liver cells. These studies have highlighted the potential usefulness of PDX-1 as a reprogramming factor of non-beta-cells toward beta-cell-like cells that can be used in diabetes cell/gene therapy.

The results of this study suggest a promising future for many diabetic patients (especially type 1) who need pancreatic beta cell transplantation.

Liu T, Wang CY, Yu F, Gou SM, Wu HS, Xiong JX, Zhou F. In vitro pancreas duodenal homeobox-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells. World J Gastroenterol 2007; 13(39): 5232-5237

Written by Sunil Rangarajan

Reviewed by Ben-Griffin Smith

Published by Pooja Ghatalia