Consequences of a compromised intrauterine environment on islet function.
Low birth weight is an important risk factor for impaired glucose tolerance and diabetes later in life. One hypothesis is that fetal beta-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 beta-cells. Pathological outcomes such as beta-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 beta-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 beta-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 beta-cell function. These findings frame our current knowledge of beta-cell developmental programing and highlight future research directions to clarify the mechanisms of beta-cell dysfunction for human IUGR.
Green
Alice S
AS
Department of Animal Sciences, University of Arizona, 1650 East Limberlost Drive, Tucson, Arizona 85719, USA.
Rozance
Paul J
PJ
Limesand
Sean W
SW
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000503:physiopathology; D004195:Disease Models, Animal; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D005865:Gestational Age; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000502:physiology*; D051379:Mice; D051381:Rats; D012307:Risk Factors; D012756:Sheep