Developmental programming of neonatal pancreatic β-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation
| Autor: | Marta Menjivar, Adriana Rodríguez-Trejo, B. Blondeau, Elena Zambrano, Carmen Méndez, Peter W. Nathanielsz, Bernadette Breant, María Guadalupe Ortiz-López, María de los Ángeles Granados-Silvestre |
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| Rok vydání: | 2012 |
| Předmět: |
Blood Glucose
Male endocrine system medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment Fluorescent Antibody Technique Cell Separation Type 2 diabetes Biology Eating Low-protein diet Pregnancy Insulin-Secreting Cells Physiology (medical) Internal medicine Diet Protein-Restricted medicine Cell separation Animals Insulin Rats Wistar Pancreas Transcription factor Cell Proliferation Insulin blood Body Weight Cell Differentiation Articles Organ Size medicine.disease Immunohistochemistry Diet Rats Endocrinology Animals Newborn Gene Expression Regulation Female Developmental programming Transcription Factors |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 302:E1431-E1439 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Maternal low-protein diets (LP) impair pancreatic β-cell development, resulting in later-life failure and susceptibility to type 2 diabetes (T2D). We hypothesized that intrauterine and/or postnatal developmental programming seen in this situation involve altered β-cell structure and relative time course of expression of genes critical to β-cell differentiation and growth. Pregnant Wistar rats were fed either control (C) 20% or restricted (R) 6% protein diets during pregnancy (1st letter) and/or lactation (2nd letter) in four groups: CC, RR, RC, and CR. At postnatal days 7 and 21, we measured male offspring β-cell fraction, mass, proliferation, aggregate number, and size as well as mRNA level for 13 key genes regulating β-cell development and function in isolated islets. Compared with CC, pre- and postnatal LP (RR) decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Isl1, Rfx6, and Slc2a2 mRNA levels. LP only in pregnancy (RC) also decreased β-cell fraction, mass, proliferation, aggregate size, and number and increased Hnf1a, Hnf4a, Pdx1, Rfx6, and Ins mRNA levels. Postnatal LP offspring (CR) showed decreased β-cell mass but increased β-cell fraction, aggregate number, and Hnf1a, Hnf4a, Rfx6, and Slc2a2 mRNA levels. We conclude that LP in pregnancy sets the trajectory of postnatal β-cell growth and differentiation, whereas LP in lactation has smaller effects. We propose that LP promotes differentiation through upregulation of transcription factors that stimulate differentiation at the expense of proliferation. This results in a decreased β-cell reserve, which can contribute to later-life predisposition to T2D. |
| Databáze: | OpenAIRE |
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