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- Title
Endocrine Pancreas Regeneration in Diabetic IGF-I Transgenic Mice Results from Replication of Pre-Existing β-Cells Rather than from Bone Marrow Cell Recruitment and Differentiation.
- Authors
Agudo, Judith; Ayuso, Eduard; Jimenez, Veronica; Salavert, Ariana; Haurigot, Virginia; Tafuro, Sabrina; Ruberte, Jesus; Segovia, Jose Carlos; Bueren, Juan; Bosch, Fatima
- Abstract
Recovery from type 1 diabetes requires restoration or β-cell mass. We have shown that transgenic mice expressing insulin-like growth factor-I (IGF-I) in β-cells regenerate β-cell mass after diabetes induction (STZ). Vascularization plays a key role in the formation of pancreatic islets and increased vascularization in VEGF transgenic mice leads to increased β-cell mass. In basal conditions, expression of VEGF was 3.5-fold higher in IGF-I transgenic compared with control islets. However, the number of capillaries within the islets were similar in both groups of mice, indicating that angiogenesis was not increased. Expression of SDF-1, a chemo-attractant for bone marrow cells (BMC), was normal in non-diabetic conditions but increased after STZ-treatment. Therefore, we also investigated whether IGF-I expression in β-cells could increase BMC recruitment and differentiation into β-cells. To this end, BMC from β-actin/green fluorescent protein (GFP) transgenic mice were transplanted into lethally irradiated IGF-I transgenic mice. GFP+ cells with an hematopoietic phenotype (CD45+) were found in the interstitium of endocrine pancreatic tissue. In contrast, very few insulin+/GFP+ cells were detected in islets from these animals. Thus, IGF-I overexpression did not result in recruitment and differentiation of BMC into β-cells. Moreover, islets from STZ-treated bone marrow transplanted transgenic mice co-expressed IGF-I, suggesting that β-cells in such islets originated, probably by replicatiun, from pre-existing β-cells. Indeed, IGF-I expressing transgenic islets showed an increase in IRS2, total AKT, P-AKT, and P-FOXO 1 that lead to decreased levels of p27 mRNA inducing higher CDK4 expression, consistent with increased β-cell replication. These data suggest that IGF-I expression regenerates the endocrine pancreas during diabetes by B-cell replication rather than BMC differentiation.
- Publication
Diabetes, 2007, Vol 56, pA424
- ISSN
0012-1797
- Publication type
Academic Journal