Protein restriction during early development enhances insulin responsiveness but selectively impairs sensitivity to insulin at low concentrations in white adipose tissue during a later pregnancy

Poor early nutrition may elicit long-term detrimental effects on adult heal th, including susceptibility to non-insulin-dependent diabetes mellitus. We investigated the impact of moderate maternal protein restriction during pr egnancy and lactation on the action of insulin on adipocyte glucose uptake in female offspring during their own pregnancies. Offspring of darns provid ed with diets containing either 200 g protein/kg or 80 g protein/kg during pregnancy and lactation (termed C and EPR groups respectively) were weaned on to 200 g protein/kg diet at 24 d of age. At 9-12 weeks of age both group s were time mated and studied at day 19 of gestation. Rates of glucose util ization (assessed using the 2-deoxy-D-[1-H-3]glucose technique) measured in five distinct adipose tissue depots (parametrial (PM), mesenteric (MES), p erirenal CPR), subcutaneous (SC), interscapular (IS)) in vivo in the post-a bsorptive state were consistently lower in early-protein-restricted (EPR) p regnant rats compared with control (C) pregnant rats. In C pregnant rats, i nsulin significantly increased glucose utilization only in the IS depot. In contrast, significantly increased glucose utilization rates in response to hyperinsulinaemia were evident in all five adipose-tissue depots of the EP R pregnant group. Consequently, glucose utilization rates in PM and SC depo ts during hyperinsulinaemia were significantly higher in EPR pregnant rats compared with C pregnant rats. Adipocytes were isolated from PM and MES dep ots to determine whether altered responses to insulin in vivo were retained in vitro. Rates of insulin-stimulated glucose uptake at sub-maximal (15 mu U/ml) and maximal (15 mU/ml) insulin concentrations were significantly hig her in both MES and PM adipocytes from EPR pregnant rats, but the sensitivi ty of glucose uptake to insulin at low concentrations was blunted compared with adipocytes from C pregnant rats. The results demonstrate that early pr otein restriction enhances the capacity for adipocyte glucose uptake at hig h insulin concentrations, but dampens the response to insulin at low physio logical concentrations.