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This Article Full Text Full Text (PDF) All Versions of this Article: JME-09-0045v1 44/1/25    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by de Miguel-Santos, L. Articles by Álvarez, C. Search for Related Content PubMed PubMed Citation Articles by de Miguel-Santos, L. Articles by Álvarez, C.

¹ Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, UCM, 28040 Madrid, Spain
² CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, Madrid, Spain
³ Departamento de Metabolismo y Nutrición, Instituto del Frío, CSIC, Madrid, Spain

(Correspondence should be addressed to C Álvarez at Departamento de Bioquímica y Biología Molecular II, Facultad de Farmacia, Universidad Complutense de Madrid, UCM; Email: calvarez{at}farm.ucm.es)

*(L de Miguel-Santos and E Fernández-Millán contributed equally to this work)

Replication, neogenesis, and apoptosis play a main role in neonatal endocrine pancreas remodeling. IGFs are major contributors to β-cell growth and function and are highly sensitive to nutritional status. We previously showed that maternal malnutrition caused an increase in β-cell mass in fetuses related to the stimulation of β-cell proliferation due to increased pancreatic IGF-1. At 4 days of life, the β-cell mass was decreased in undernourished neonates and persisted until adult age. To clarify whether undernutrition disrupts islet remodeling, we quantified β-cell mass, neogenesis, replication, and apoptosis on days 4, 14, and 23. To determine the impact of food restriction on IGF ontogeny and the consequences for β-cell growth, we measured IGF-1/-2 protein content in pancreas and liver and pancreatic IGF-1 receptor (IGF-1R)-signaling pathway at the same days. Our results indicate that undernutrition alters the timing and intensity of neonatal β-cell ontogeny. However, although malnutrition causes β-cell deficiency in neonates, an active process of β-cell neogenesis and a lower incidence of β-cell apoptosis maintain the regenerative capacity of the endocrine pancreas. Interestingly, our data provide evidence that local production of IGFs seems to be instrumental in these processes. In particular, increased pancreatic IGF-2 in undernourished rats may contribute to the partial suppression of the developmental wave of β-cell apoptosis probably through the inhibition of glycogen synthase kinase-3. In addition, decreased pancreatic levels of IGFBP-1/-2/-3 in undernourished neonates could enhance IGF availability for interacting with IGF-1R/IR.