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1 Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
* To whom correspondence should be addressed. E-mail: sdevaskar{at}mednet.ucla.edu.
We examined the long term effect of in-utero exposure to streptozotocin-induced maternal diabetes on the progeny that postnatally received either ad lib access to milk by being fed by control mothers (CM/DP) or was subjected to relative nutrient restriction by being fed by diabetic mothers (DM/DP), when compared to the control progeny fed by control mothers (CM/CP). There was increased food intake, glucose intolerance and obesity in the CM/DP group and diminished food intake, glucose tolerance and postnatal growth restriction in the DM/DP group, persisting in the adult. These changes were associated with aberrations in hormonal and metabolic profiles, and alterations in hypothalamic neuropeptide Y concentrations. Employing sub-fractionation and Western blot analysis, the CM/DP group demonstrated a higher skeletal muscle sarcolemma-associated (d1 and d60) and white adipose tissue plasma membrane associated (d60) GLUT 4 in the basal state with a lack of insulin-induced translocation. The DM/DP group demonstrated a partial amelioration of this change observed in the CM/DP group. We conclude that the offspring of a diabetic mother with ad lib postnatal nutrition demonstrates increased food intake and resistance to insulin-induced translocation of GLUT 4 in skeletal muscle and white adipose tissue. This in turn leads to glucose intolerance and obesity at a later stage (d180). Postnatal nutrient restriction results in reversal of this adult phenotype, thereby explaining the phenotypic heterogeneity that exists in this population.
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