title: 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.
abstract: Poor early nutrition may elicit long-term detrimental effects on adult health, including susceptibility to non-insulin-dependent diabetes mellitus. We investigated the impact of moderate maternal protein restriction during pregnancy and lactation on the action of insulin on adipocyte glucose uptake in female offspring during their own pregnancies. Offspring of dams provided 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 groups were time-mated and studied at day 19 of gestation. Rates of glucose utilization (assessed using the 2-deoxy-D-[1-3H]glucose technique) measured in five distinct adipose tissue depots (parametrial (PM), mesenteric (MES), perirenal (PR), subcutaneous (s.c.), interscapular (IS)) in vivo in the post-absorptive state were consistently lower in early-protein-restricted (EPR) pregnant rats compared with control (C) pregnant rats. In C pregnant rats, insulin 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 EPR pregnant group. Consequently, glucose utilization rates in PM and s.c. depots during hyperinsulinaemia were significantly higher in EPR pregnant rats compared with C pregnant rats. Adipocytes were isolated from PM and MES depots to determine whether altered responses to insulin in vivo were retained in vitro. Rates of insulin-stimulated glucose uptake at sub-maximal (15 microU/ml) and maximal (15 mU/ml) insulin concentrations were significantly higher in both MES and PM adipocytes from EPR pregnant rats, but the sensitivity of glucose uptake to insulin at low concentrations was blunted compared with adipocytes from C pregnant rats. The results demonstrate that early protein restriction enhances the capacity for adipocyte glucose uptake at high insulin concentrations, but dampens the response to insulin at low physiological concentrations.
authors.affiliation: Division of Biomedical Science, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, London, UK. m.j.holness@qmw.ac.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Holness
authors.forename: L G
authors.initials: LG
authors.lastname: Fryer
authors.forename: M C
authors.initials: MC
authors.lastname: Sugden
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D018753:Diet, Protein-Restricted; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics*; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose