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Am J Physiol Regul Integr Comp Physiol (October 28, 2004). doi:10.1152/ajpregu.00206.2004
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Submitted on March 29, 2004
Accepted on October 21, 2004

Maternal protein restriction leads to hyperinsulinemia and reduced insulin signalling protein expression in 21 month-old female rat offspring

D. S Fernandez-Twinn1*, A. Wayman1, S. Ekizoglou1, M. S Martin1, C. N Hales1, and S. E Ozanne1

1 Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom

* To whom correspondence should be addressed. E-mail: df220{at}cam.ac.uk.

Human adult diseases such as cardiovascular disease, hypertension and type-2 diabetes have been epidemiologically linked to poor fetal growth and development. Male offspring of rat dams fed a low protein (LP) diet during pregnancy and lactation develop diabetes with concomitant alterations in their insulin signalling mechanisms. Such associations have not been studied in female offspring. The aim of this study was to determine if female LP offspring develop diabetes in later life. Control and LP female offspring groups were obtained from rat dams fed a control (20% protein) or an isocaloric (8% protein) diet respectively, throughout pregnancy and lactation. Both groups were weaned and maintained on 20% normal laboratory chow until 21 months of age when they underwent intravenous glucose tolerance testing (IVGTT). Fasting glucose was comparable between the 2 groups, however, LP fasting insulin was approximately 2-fold that of controls (p<0.02). Glucose tolerance during IVGTT was comparable between the two groups. However, LP peak plasma insulin at 4 min was approximately 3-fold higher than in controls (p<0.001). LP plasma insulin area under the curve (AUC) was 1.9 fold higher than controls (p<0.02). In western blots, both muscle PKC-{zeta} expression and p110{beta}-associated p85{alpha} in abdominal fat was reduced (p<0.05) in LPs. Hyperinsulinemia in response to glucose challenge coupled with attenuation of certain insulin signalling molecules imply the development of insulin resistance in LP muscle and fat. These observations suggest that intrauterine protein restriction leads to insulin resistance in females in old age and hence, an increased risk of type-2 diabetes.




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