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Induction of Insulin-producing beta-cells Regeneration in vivo

Objective

Diabetes has become one of the most widespread metabolic disorders with epidemic dimensions affecting almost 6% of the world’s population. Despite modern treatments, the life expectancy of patients with Type 1 diabetes remains reduced as compared to healthy subjects. There is therefore a need for alternative therapies. Towards this aim, using the mouse, we recently demonstrated that the in vivo forced expression of a single factor in pancreatic alpha-cells is sufficient to induce a continuous regeneration of alpha-cells and their subsequent conversion into beta-like cells, such converted cells being capable of reversing the consequences of chemically-induced diabetes in vivo (Collombat et al. Cell, 2009).

The PI and his team therefore propose to further decipher the mechanisms involved in this alpha-cell-mediated beta-cell regeneration process and determine whether this approach may be applied to adult animals and whether it would efficiently reverse Type 1 diabetes. Furthermore, a major effort will be made to verify whether our findings could be translated to human. Specifically, we will use a tri-partite approach to address the following issues: (1) Can the in vivo alpha-cell-mediated beta-cell regeneration be induced in adults mice? What would be the genetic determinants involved? (2) Can alpha-cell-mediated beta-cell regeneration reverse diabetes in the NOD Type 1 diabetes mouse model? (3) Can adult human alpha-cells be converted into beta-like cells?

Together, these ambitious objectives will most certainly allow us to gain new insight into the mechanisms defining the identity and the reprogramming capabilities of mouse and human endocrine cells and may thereby open new avenues for the treatment of diabetes. Similarly, the determination of the molecular triggers implicated in the beta-cell regeneration observed in our diabetic mice may lead to exciting new findings, including the identification of “drugable” targets of importance for human diabetic patients.

Field of science

  • /medical and health sciences/clinical medicine/endocrinology/diabetes

Call for proposal

ERC-2011-StG_20101109
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Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Address
Rue De Tolbiac 101
75654 Paris
France
Activity type
Research Organisations
EU contribution
€ 1 500 000
Principal investigator
Patrick Collombat (Dr.)
Administrative Contact
Dominique Nobile (Mr.)

Beneficiaries (1)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
EU contribution
€ 1 500 000
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Principal investigator
Patrick Collombat (Dr.)
Administrative Contact
Dominique Nobile (Mr.)