Diabetes, pathways and mechanisms of beta-cell regeneration and proliferation

TITOLO DEL PROGETTO

Pathways and mechanisms of beta-cell re generation and proliferation in type 1 and 2 diabetes

RESPONSABILE

Prof Francesco Dotta

PREMESSA

Increasing evidence indicates that decreased functional beta-cell mass is the hallmark of both type 1 and type 2 diabetes mellitus. This underlines the absolute or relative insulin deficiency in both conditions. The beta-cell mass is thought to be controlled by a balance between islet cell neogenesis, proliferation, and remodeling by apoptosis.

OBIETTIVI

Overall objective of the present grant proposal aims at analyzing islet/beta cell regeneration and proliferation in order to gain insights into possible mechanisms and molecular pathways involved in the regulation of the beta cell mass and function and to optimize strategies to obtain insulin-producing glucose-responsive cells. In the light that Hedgehog signalling pathway plays an important role both in endocrine pancreas development and in the regulation of insulin secretion in beta cell lines, we'll mainly focus our attention to this pathway.

TEMPISTICA

inizio e conclusione: 2007

METODOLOGIA

Studies will be performed in 3 different settings:
1. Purified pancreatic islets from multiorgan donors (both normal and type 2 diabetic donors);
2. Frozen and/or formalin-fixed/paraffin embedded pancreatic samples from islet autoantibody-positive donors as well as from control and type 2 diabetic donors;
3. INS-1 cell line.


RISULTATI

A better understanding of the mechanisms involved in the beta-cell re generation and proliferation would favor the development of strategies aimed to prevent diabetes and/or relenting its progression. In the light that loss of beta cells has been to occur both in type 1 and type 2 diabetes, the identification and characterization of pathways regulating beta cell mass may provide important therapeutic insights in both these forms of diabetes. In the present grant proposal we will obtain potentially important information both from normal and diseased pancreatic tissue, and we plan to dissect at molecular level the role of Hedgehog signalling in the regulation of beta cell mass.

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