Issue 104 Item 8 Intestinal Cells Can Be Stimulated To Make Insulin

Dr. Norman Wong, a University of Calgary physician-scientist, and his colleagues, Drs. Takaaki Nakamura and Atsunori Kashiwagi, clinician-scientists of Shiga University in Japan, have completed studies which demonstrate that intestinal cells can be stimulated into producing insulin –- a hormone that millions of diabetics are lacking.

The team’s findings are published in the May edition of Diabetes.

“Scientists the world over are studying how to manipulate cells in order to convert them into pancreatic cells, which may be used to treat diabetes mellitus,” says Wong, professor, medicine, and biochemistry & molecular biology, University of Calgary Faculty of Medicine, and director, Libin Gene Therapy Unit. “My colleagues and I decided to investigate whether we could make islet cells by altering intestinal cells so that they would transform into pancreatic islet cells and produce insulin.”

Type 1 diabetes mellitus, previously known as juvenile diabetes mellitus, is caused by the destruction of insulin-producing beta cells in the pancreas. This destruction occurs when the immune system mistakenly attacks the beta cells. The absence of insulin means that people with diabetes have high blood glucose and associated complications that affect vital organs including: kidney, eye and nerve conditions as well as heart and vascular disease.

This research stems from the understanding that pancreatic cells and intestinal cells share a common origin in the embryo. Armed with that knowledge, the team began exploring whether conducting a series of experiments on intestinal cells would stimulate those cells into performing the functions normally provided by pancreatic cells.

The scientists first exposed the intestinal cells of rats to a transcription factor called PDX-1. This factor has been previously shown to be important for insulin gene expression. Secondly, the team exposed the PDX-1 expressing intestinal cells to a growth factor called Betacellulin. “We discovered that the combination of those two steps enabled us to fire up the intestinal cells so that they produced insulin,” says Wong.

“The advantage of using intestinal cells to perform the work of pancreatic cells is that people have available to them a nearly limitless supply of their own intestinal cells -– whereas pancreatic cells are extremely scarce,” says Wong. “That’s what’s so exciting about these results –- we have taken the first step in finding a man-made way to produce pancreatic cells. These findings may provide an important source of cells for the Edmonton islet cell transplantation protocol.”

Wong’s research is supported by: Canadian Diabetes Association, Alberta Heritage Foundation for Medical Research, and Canadian Institutes of Health Research.