Document Detail

Developmental programming of neonatal pancreatic β-cells by a maternal low-protein diet in rats involves a switch from proliferation to differentiation.
MedLine Citation:
PMID:  22436693     Owner:  NLM     Status:  MEDLINE    
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.
Adriana Rodríguez-Trejo; María Guadalupe Ortiz-López; Elena Zambrano; María de Los Ángeles Granados-Silvestre; Carmen Méndez; Bertrand Blondeau; Bernadette Bréant; Peter W Nathanielsz; Marta Menjivar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-20
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  302     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-04     Completed Date:  2012-08-03     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E1431-9     Citation Subset:  IM    
Universidad Nacional Autónoma de México. Av. Universidad 3000, Facultad de Química, Mexico City, Mexico.
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MeSH Terms
Animals, Newborn
Blood Glucose / metabolism
Body Weight / drug effects
Cell Differentiation / drug effects*
Cell Proliferation / drug effects*
Cell Separation
Diet, Protein-Restricted*
Eating / drug effects
Fluorescent Antibody Technique
Gene Expression Regulation / drug effects
Insulin / blood
Insulin-Secreting Cells / drug effects*
Organ Size / drug effects
Pancreas / cytology,  drug effects,  growth & development
Rats, Wistar
Transcription Factors / biosynthesis,  genetics
Reg. No./Substance:
0/Blood Glucose; 0/Insulin; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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