Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-1-18
pubmed:abstractText
Low birth weight has been reported to be associated with impaired insulin secretion and insulin resistance. It has been proposed that this association results from fetal programming in response to the intrauterine environment (the thrifty phenotype hypothesis). To elucidate the relationship between birth weight and genetically determined defects in insulin secretion, we measured the birth weights of neonates derived from crosses of male pancreatic beta-cell type glucokinase knockout (Gck+/-) mice and female wild-type (WT) or Gck+/- mice. In 135 offspring, birth weights were lower in the presence of a fetal heterozygous mutation and higher in the presence of a maternal heterozygous mutation. Moreover, Gck-/- neonates had significantly smaller birth weights than WT or Gck+/- neonates (means +/- SE 1.49+/-0.03 [n = 30] vs. 1.63+/-0.03 [n = 30] or 1.63+/-0.02 [n = 50] g, respectively; P<0.01). Thus, Gck mutations in beta-cells may impair insulin response to glucose and alter intrauterine growth as well as glucose metabolism after birth. This study has confirmed the results of a previous report that human subjects carrying mutations in Gck had reduced birth weights and has provided direct evidence for a link between insulin and fetal growth. Moreover, birth weights were reduced in insulin receptor substrate-1 knockout mice despite normal insulin levels. Taken together, these results suggest that a genetically programmed insulin effect during embryogenesis determines fetal growth and provides a possible molecular link between birth weight and susceptibility to type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
82-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Insulin effect during embryogenesis determines fetal growth: a possible molecular link between birth weight and susceptibility to type 2 diabetes.
pubmed:affiliation
Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't