Differential effects of prenatal and postnatal nutritional environment on ß-cell mass development and turnover in male and female rats.
Fetal nutrient and growth restriction is associated with development of type 2 diabetes. Although the exact mechanisms responsible for this association remain debated, intrauterine and/or postnatal maldevelopment of β-cell mass has been proposed as a potential mechanism. To address this hypothesis, β-cell mass development and turnover was assessed in rats exposed to either intrauterine and/or postnatal caloric/growth restriction. In total, four groups of male and female Sprague Dawley rats (n = 69) were developed and studied: 1) control rats, i.e. control mothers rearing control pups; 2) intrauterine calorically and growth-restricted rats, i.e. 50% prenatal calorically restricted pups cross-fostered to control mothers; 3) postnatal calorically and growth-restricted rats, i.e. 50% calorically restricted mothers rearing pups born to control mothers; and 4) prenatal and postnatal calorically and growth restricted rats, i.e. 50% calorically restricted mothers rearing intrauterine 50% calorically restricted pups. Intrauterine growth restriction resulted in approximately 45% reduction of postnatal β-cell fractional area and mass characterized by reduced rate of β-cell replication and decreased evidence of neogenesis. In contrast, β-cell fractional area and weight-adjusted β-cell mass in postnatal growth restriction was approximately 30% higher than in control rats. Rats exposed to both intrauterine and postnatal caloric and growth restriction demonstrated approximately 80% decrease in β-cell mass, reduction in β-cell replication, and decreased evidence of neogenesis compared with control. Neither intrauterine nor postnatal caloric restriction significantly affected the rate of β-cell apoptosis. These data support the hypothesis that intrauterine maldevelopment of β-cell mass may predict the increased risk of type 2 diabetes in adult life.
Larry L. Hillblom Islet Research Center, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095, USA. amatveyenko@mednet.ucla.edu
Aleksey V
AV
Matveyenko
Inderroop
I
Singh
Bo-Chul
BC
Shin
Senta
S
Georgia
Sherin U
SU
Devaskar
D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D049109:Cell Proliferation; D003924:Diabetes Mellitus, Type 2; D005260:Female; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics