Beta cells in the liver

Lead Research Organisation: University of Bath
Department Name: Biology and Biochemistry

Abstract

In addition to the normal channels of scientific publication and communication at scientific meetings, we shall take advantage of opportunities to publicise this work to the general public as an example of how basic research may lead to clinical innovation.
A film featuring this project has already been made (but not edited) by an independent filmmaker working under the auspices of the University of Bath. This, together with other short films featuring innovations in science and engineering at the University, is intended for use in secondary schools.

Technical Summary

Diabetes remains a common condition that causes enormous suffering worldwide and costs health care systems vast sums of money. Although diabetes is a complex group of diseases, a significant proportion of patients end up receiving insulin therapy as the patient cannot produce enough to meet the bodya??s requirements. Because most of the complications of diabetes arise from inadequate control of blood glucose, there is a need to develop new therapies which can increase the number or activity of beta cells in the patient.
We have previously shown that a fusion protein, Pdx1-VP16, can induce transformation of liver to pancreas in transgenic Xenopus tadpoles. Recently we have obtained preliminary results showing that the reagent also works in adult mice.
This project will utilise mice and will have the following objectives:
a?? To characterize the beta-like cells more fully.
a?? To establish a reliable dose-response relationship.
a?? To investigate the cell lineage of the beta-like cells.
a?? To find whether the procedure can cure experimental diabetes.
The ultimate object is to develop a method for causing the formation of beta cells in the liver which could be developed as a novel therapy for diabetes.

Publications

10 25 50
publication icon
Burke ZD (2010) Isolation and culture of embryonic pancreas and liver. in Methods in molecular biology (Clifton, N.J.)

publication icon
Coad RA (2009) Inhibition of Hes1 activity in gall bladder epithelial cells promotes insulin expression and glucose responsiveness. in Biochemistry and cell biology = Biochimie et biologie cellulaire

publication icon
Dutton JR (2007) Beta cells occur naturally in extrahepatic bile ducts of mice. in Journal of cell science

publication icon
Eberhard D (2008) Transdifferentiation and metaplasia as a paradigm for understanding development and disease. in Cellular and molecular life sciences : CMLS

publication icon
Eberhard D (2008) Origin of pancreatic endocrine cells from biliary duct epithelium. in Cellular and molecular life sciences : CMLS

publication icon
O'Neill KE (2008) Origin of beta-cells in regenerating pancreas. in BioEssays : news and reviews in molecular, cellular and developmental biology

publication icon
Slack JM (2009) Metaplasia and somatic cell reprogramming. in The Journal of pathology

publication icon
Slack JM (2008) Origin of stem cells in organogenesis. in Science (New York, N.Y.)

publication icon
Slack JM (2007) Metaplasia and transdifferentiation: from pure biology to the clinic. in Nature reviews. Molecular cell biology