title: Maternal undernutrition increases pancreatic IGF-2 and partially suppresses the physiological wave of {beta}-cell apoptosis during the neonatal period.
abstract: Replication, neogenesis, and apoptosis play a main role in neonatal endocrine pancreas remodeling. IGFs are major contributors to beta-cell growth and function and are highly sensitive to nutritional status. We previously showed that maternal malnutrition caused an increase in beta-cell mass in fetuses related to the stimulation of beta-cell proliferation due to increased pancreatic IGF-1. At 4 days of life, the beta-cell mass was decreased in undernourished neonates and persisted until adult age. To clarify whether undernutrition disrupts islet remodeling, we quantified beta-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 beta-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 beta-cell ontogeny. However, although malnutrition causes beta-cell deficiency in neonates, an active process of beta-cell neogenesis and a lower incidence of beta-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 beta-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.
authors: Departamento de Bioquímica y Biología Molecular II, Universidad Complutense de Madrid, Spain.
authors: Laura
authors: L
authors: de Miguel-Santos
authors: Elisa
authors: E
authors: Fernández-Millán
authors: María
authors: M
authors: Angeles Martín
authors: Fernando
authors: F
authors: Escrivá
authors: Carmen
authors: C
authors: Alvarez
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D044342:Malnutrition / Q000378:metabolism*; D039382:Maternal Nutritional Physiological Phenomena; D010179:Pancreas / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007335:Insulin-Like Growth Factor II