title: Endocrine pancreas development: effects of metabolic and intergenerational programming caused by a protein-restricted diet.
abstract: Experimental studies have demonstrated an association between low birth weight and the later development of type 2 diabetes. This association could be a result of the programming process that affects pancreatic beta-cell development due to poor fetal nutrition. This mechanism may not be limited to the first generation. In rodents, endocrine cells of the pancreas are derived from cells of the endodermal dorsal and ventral anlage that migrate and gather in clusters in a process termed isletogenesis. Islet development occurs relatively late in gestation, and islets undergo substantial remodeling immediately after birth under the regulation of a transcription factor network. Furthermore, the offspring of mice fed a protein-restricted diet exhibit a reduced pancreatic beta-cell mass at birth, lower vascularization, increased apoptosis rate, and changes in glucose metabolism in later life. Although the mechanisms underlying these relationships are unclear, it has been hypothesized that in utero nutritional conditions affect epigenetic patterns of gene transcription that persist throughout life and subsequent generations. We aimed to review the process of the formation of the endocrine pancreas in rodents, the consequences of a protein-restricted diet on offspring, and the transgenerational effects of this insult on the incidence of type 2 diabetes.
authors.affiliation: Laboratory of Morphometry and Cardiovascular Morphology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Eliete Dalla Corte
authors.initials: ED
authors.lastname: Frantz
authors.forename: Nayara
authors.initials: N
authors.lastname: Peixoto-Silva
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pinheiro-Mulder
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D018753:Diet, Protein-Restricted; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000196:embryology* / Q000378:metabolism*; D008659:Metabolic Diseases / Q000235:genetics; D051379:Mice; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein