[36] Diabetes and Gene Regulation

Our group is interested in defining the factors (nutrients,hormones,neuropeptides,...) which determine the regulation of the genes coding to the majors hormones involved in glucose homeostasis, insulin and glucagons, the mechanisms by which they exert their effects and the transcription factors involved.

Development and differentiation of glucagon-producing cells in the endocrine pancreas:
The mechanisms by which the glucagon-producing cells appear and differentiate are unclear.Our hypothesis is that these cells develop by a default pathway, in the absence of beta and delta cell-specific factors, such as Pdx-1 and Pax-4 which are critical for the development of these 2 cell types. We investigate this hypothesis by studies both in cell lines and transgenic animals.

Molecular basis of diabetes:
We have investigated the genetic basis of MODY (Maturity-Onset Diabetes of the Young) in Switzerland as well the molecular basis of cases of pancreas agenesis and severe insulin resistance. We are pursuing this analysis of human gene defects involved in disorders of glucose homeostasis.

Molecular diagnosis of islet graft rejection in humans:
The diagnosis of islet graft rejection is presently impossible.We have designed a molecular marker which reflects beta cell loss after islet transplantation. We are currently investigating whether this test is sensitive and clinically adequate to diagnose rejection of islet transplantation.