Type 2 diabetes is a very common disease in most countries around the
word, and its prevalence is presently raising. The seriousness of type 2
diabetes "epidemics" depends on both the high mortality rate and the
devastating morbidity of its complications. In addition, the economic
costs of diabetes have become astonishing and can no longer be tolerated.
Despite this huge burden, there is currently no cure for diabetes. Thus,
efforts to prevent and ultimately to cure type 2 diabetes, the more common
form of diabetes, have the potential to be very rewarding in term of
avoidance of human suffering and to be extremely cost-effective as well.
Current attempts to reach these goals have had only limited success. This
is largely due to the fact that the causes of most forms of type 2
diabetes (with the exception of the monogenic forms) are ultimately
unknown.
Type 2 diabetes is determined by abnormalities in either a single gene,
or, more frequently, in multiple genes. Under appropriate environmental
conditions, these abnormalities impair glucose metabolism leading to
chronic hyperglycemia. In most affected patients, the gene(s) causing
susceptibility to type 2 diabetes is still unknown, however. It has
recently been shown that the function of the PED gene is commonly
increased in type 2 diabetics. In transgenic animal models, this same
defect may lead to diabetes by impairing insulin action on adipose tissue
and/or insulin secretion by the pancreatic beta-cells. At the IEOS, the
mechanism of PED dysregulation of insulin action has been extensively
investigated over the past several years (fig. 1). Thus, research is now
focusing on the mechanisms responsible for the impaired beta-cell
function. In addition, we wish to identify the contribution of adipose
tissue and beta-cell districts to PED-caused derangement in glucose
utilization. This effort is being implemented in the context of the EUDG
Consortium, an EC-funded program networking eight reknown Institutions
dedicated to diabetes research in six European countries. The
investigation of PED gene defect in the beta-cells includes the analysis
of in vitro beta-cell models producing abnormally high levels of the
product of PED gene. Major signalling mechanisms controlling beta-cell
functions will be compared in these cells and in beta-cells with no PED
defect, to discover those mechanisms which are impaired by PED
abnormality. Further transgenic mice bearing PED gene defect selectively
in the adipose tissue or in the beta-cells will also be generated.
Analysis of these animals will reveal which tissue causes deranged glucose
utilization when PED gene features abnormal function. These new
information will enable us, in the future, to devise targeted strategies
to correct PED gene defect in individuals with type 2 diabetes, and to
prevent its consequences.
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