Maria Remedi
Research
KATP channels are the critical link between glucose metabolism
and insulin secretion in pancreatic b-cells. In humans, mutations
in the b-cell KATP channels can underlie Permanent Neonatal
Diabetes Mellitus (PNDM). By contrast, loss-of-function mutations
of b-cell KATP channel subunits (SUR1, Kir6.2) causes congenital
Hyperinsulinemia (HI), a rare genetic disease characterized
by high insulin levels in parallel with low blood glucose.
The manipulation by gene transfer of ion channels in pancreatic
?-cells or the use of transgenic animals models that we have
generated in our laboratory (mice which overexpress, underexpress
or have mutations in the KATP channel) permits me the exciting
possibility of exploring, in more detail, the consequences
of KATP channel alterations in the development of type-2 diabetes,
PNDM or HI. Hyperinsulinemia can precede the development of
diabetes and, interestingly, many HI patients can cross-over
to a diabetic phenotype in later life. Type-2 diabetes requires
interaction of genetic and environmental factors for its development.
Since one of the major causal factors in the development
of hyperinsulinemia and insulin resistance is the high-fat
diet and the consequent obesity, which precede type-2 diabetes
in genetically predisposed individuals, I am also interested
in the consequences of high-fat feeding on diabetic or hyperinsulinemic
transgenic mice. Thus, by feeding transgenic mice with a high-fat
diet I can directly examine the temporal progression of ?-cell
function and the contribution of genetic and environmental
factors in the development of these diseases. Better identification
of these factors and understanding of how they are involved
in the signaling cascade that connects glucose metabolism
and insulin secretion may have significant implications in
diabetes and HI therapy.
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