Antecedent protein restriction exacerbates development of impaired insulin action after high-fat feeding.
The study investigated whether a persistent impairment of insulin secretion resulting from mild protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of the diabetogenic challenge of high-fat feeding. Offspring of dams provided with either control (20% protein) diet (C) or an isocaloric restricted (8%) protein diet (PR) were weaned onto the maintenance diet with which their mothers had been provided. At 20 wk of age, protein restriction enhanced glucose tolerance despite impaired insulin secretion and an augmented and sensitized lipolytic response to norepinephrine in adipocytes. C and PR rats were then transferred to a high-fat diet (HF, 19% protein, 22% lipid, 34% carbohydrate) and sampled after 8 wk. These groups are termed C-HF and PR-HF. Glucose tolerance was impaired in PR-HF, but not C-HF, rats. Insulin-stimulated glucose disposal rates were significantly lower (by 30%; P < 0.01) in the PR-HF group than in the C-HF group, and a specific impairment of antilipolytic response of insulin was unmasked in adipocytes from PR-HF, but not C-HF, rats. The study demonstrates that antecedent protein restriction accelerates and augments the development of impaired glucoregulation and insulin resistance after high-fat feeding.
Holness
M J
MJ
Molecular and Cellular Biology, Division of Biomedical Sciences, St Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, University of London, London E1 4NS, United Kingdom.
Sugden
M C
MC
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D004044:Dietary Proteins / Q000008:administration & dosage*; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D005947:Glucose / Q000502:physiology; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000209:etiology; D006946:Hyperinsulinism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D004041:Dietary Fats; D004044:Dietary Proteins; D007328:Insulin; D005947:Glucose; D009638:Norepinephrine