Consequences of a compromised intrauterine environment on islet function

Alice S. Green, Paul J. Rozance, Sean W Limesand

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Low birth weight is an important risk factor for impaired glucose tolerance and diabetes later in life. One hypothesis is that fetal β-cells inherit a persistent defect as a developmental response to fetal malnutrition, a primary cause of intrauterine growth restriction (IUGR). Our understanding of fetal programing events in the human endocrine pancreas is limited, but several animal models of IUGR extend our knowledge of developmental programing in β-cells. Pathological outcomes such as β-cell dysfunction, impaired glucose tolerance, and diabetes are often observed in adult offspring from these animal models, similar to the associations of low birth weight and metabolic diseases in humans. However, the identified mechanisms underlying β-cell dysfunction across models and species are varied, likely resulting from the different methodologies used to induce experimental IUGR, as well as from intraspecies differences in pancreas development. In this review, we first present the evidence for human β-cell dysfunction being associated with low birth weight or IUGR. We then evaluate relevant animal models of IUGR, focusing on the strengths of each, in order to define critical periods and types of nutrient deficiencies that can lead to impaired β-cell function. These findings frame our current knowledge of β-cell developmental programing and highlight future research directions to clarify the mechanisms of β-cell dysfunction for human IUGR.

Original languageEnglish (US)
Pages (from-to)211-224
Number of pages14
JournalJournal of Endocrinology
Volume205
Issue number3
DOIs
StatePublished - Jun 2010

Fingerprint

Low Birth Weight Infant
Growth
Glucose Intolerance
Animal Models
Fetal Nutrition Disorders
Metabolic Diseases
Adult Children
Fetal Development
Islets of Langerhans
Pancreas
Food

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Consequences of a compromised intrauterine environment on islet function. / Green, Alice S.; Rozance, Paul J.; Limesand, Sean W.

In: Journal of Endocrinology, Vol. 205, No. 3, 06.2010, p. 211-224.

Research output: Contribution to journalArticle

Green, Alice S. ; Rozance, Paul J. ; Limesand, Sean W. / Consequences of a compromised intrauterine environment on islet function. In: Journal of Endocrinology. 2010 ; Vol. 205, No. 3. pp. 211-224.
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