Research project P4/21 (Research action P4)
Diabetes results from an insufficiency of the insulin-producing BETA cells. Several genetic and environmental agents have been associated with the disease but their role in the pathogenesis has not yet been clarified. The pathologic process in the endocrine pancreas is only detected at a late stage, and its sequence of events has been difficult to investigate. A better understanding of the cellular and molecular basis of the glucostat function in human B cells and of the mechanisms leading to its impairment should lead to methods for earlier diagnosis and to strategies for prevention and better treatment of the disease. The objective of the present program is to investigate the regulatory pathways in human BETA cells and identify environmental conditions which can cause a BETA cell failure, either through cell destruction or functional impairment. We will specifically examine the role of a nutrient excess, of an insufficient G-protein associated receptor function and of an exposure to selected immune interactions in the disease process at the level of the BETA cells. The studies on isolated BETA cells and islet tissue should identify pathogenic conditions and their action mechanisms, which is necessary for a better understanding of the pathogenesis of diabetes and for conceiving methods for early diagnosis and prevention. The in vitro experiments will also indicate the conditions for establishing animal models of the human disease, in which strategies for prevention and treatment can be developed and assessed, both on in vivo parameters and at the level of the pancreatic BETA cells.
