title: Growth arrest specific protein (GAS) 6: a role in the regulation of proliferation and functional capacity of the perinatal rat beta cell.
abstract: OBJECTIVE
  Maternal low-protein (LP) diet during gestation results in a reduced beta cell mass in the offspring at birth and this may hamper the ability to adapt to high-energy food and sedentary lifestyle later in life. To investigate the biology behind the LP-offspring phenotype, this study aimed to identify differentially expressed genes in the pancreas and their potential role in the fetal programming.
  
  
  METHODS
  Wistar rats were given either an LP diet or normal-chow (NC) diet during gestation and differentially expressed genes in the offspring around the time of birth were identified using RNA microarray and quantitative PCR. The role of a differentially expressed gene, growth arrest specific protein 6 (GAS6), was evaluated in vitro using neonatal rat islets.
  
  
  RESULTS
  The mRNA level of Gas6, known to be mitogenic in other tissues, was reduced in LP offspring. The mRNA content of Mafa was increased in LP offspring suggesting an early maturation of beta cells. When applied in vitro, GAS6 increased proliferation of neonatal pancreatic beta cells, while reducing glucose-stimulated insulin secretion without changing the total insulin content of the islets. In addition, GAS6 decreased the mRNA content of Mafa.
  
  
  CONCLUSIONS
  We propose a role for GAS6 in the regulation of pancreatic beta cells in the critical period around the time of birth. Our results support the hypothesis that the reduced beta cell mass seen in LP offspring is caused by a change in the intra-uterine environment that favours premature maturation of the beta cells.
authors: Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Panum Institute, Blegdamsvej 3b, Building 6.5, 2200 Copenhagen, Denmark.
authors: T N
authors: TN
authors: Haase
authors: M
authors: M
authors: Rasmussen
authors: C A M
authors: CA
authors: Jaksch
authors: L W
authors: LW
authors: Gaarn
authors: C K
authors: CK
authors: Petersen
authors: N
authors: N
authors: Billestrup
authors: J H
authors: JH
authors: Nielsen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D049109:Cell Proliferation; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000166:cytology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008297:Male; D018811:Maternal Exposure; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017208:Rats, Wistar; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D000099255:Growth Arrest-Specific Protein 6