Dataset Information

Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age.

ABSTRACT:

Objective

Low birth weight is associated with diabetes in adult life. Accelerated or "catch-up" postnatal growth in response to small birth size is thought to presage disease years later. Whether adult disease is caused by intrauterine beta-cell-specific programming or by altered metabolism associated with catch-up growth is unknown.

Research design and methods

We generated a new model of intrauterine growth restriction due to fatty acid synthase (FAS) haploinsufficiency (FAS deletion [FASDEL]). Developmental programming of diabetes in these mice was assessed from in utero to 1 year of age.

Results

FASDEL mice did not manifest catch-up growth or insulin resistance. beta-Cell mass and insulin secretion were strikingly increased in young FASDEL mice, but beta-cell failure and diabetes occurred with age. FASDEL beta-cells had altered proliferative and apoptotic responses to the common stress of a high-fat diet. This sequence appeared to be developmentally entrained because beta-cell mass was increased in utero in FASDEL mice and in another model of intrauterine growth restriction caused by ectopic expression of uncoupling protein-1. Increasing intrauterine growth in FASDEL mice by supplementing caloric intake of pregnant dams normalized beta-cell mass in utero.

Conclusions

Decreased intrauterine body size, independent of postnatal growth and insulin resistance, appears to regulate beta-cell mass, suggesting that developing body size might represent a physiological signal that is integrated through the pancreatic beta-cell to establish a template for hyperfunction in early life and beta-cell failure with age.

SUBMITTER: Chakravarthy MV

PROVIDER: S-EPMC2551680 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Publications

Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age.

Chakravarthy Manu V MV Zhu Yimin Y Wice Mitchell B MB Coleman Trey T Pappan Kirk L KL Marshall Connie A CA McDaniel Michael L ML Semenkovich Clay F CF

Diabetes 20080630 10

<h4>Objective</h4>Low birth weight is associated with diabetes in adult life. Accelerated or "catch-up" postnatal growth in response to small birth size is thought to presage disease years later. Whether adult disease is caused by intrauterine beta-cell-specific programming or by altered metabolism associated with catch-up growth is unknown.<h4>Research design and methods</h4>We generated a new model of intrauterine growth restriction due to fatty acid synthase (FAS) haploinsufficiency (FAS dele ...[more]

PMID: 18591393

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Dataset Information

Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age.

Objective

Research design and methods

Results

Conclusions

Publications

Decreased fetal size is associated with beta-cell hyperfunction in early life and failure with age.

Similar Datasets

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