A low-protein diet combined with low-dose endotoxin leads to changes in glucose homeostasis in weanling rats

Robert H. J. Bandsma*, Cameron Ackerley, Khajag Koulajian, Ling Zhang, Tim van Zutphen, Theo H. van Dijk, Changting Xiao, Adria Giacca, Gary F. Lewis

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    5 Citations (Scopus)

    Abstract

    Severe malnutrition is a leading cause of global childhood mortality, and infection and hypoglycemia or hyperglycemia are commonly present. The etiology behind the changes in glucose homeostasis is poorly understood. Here, we generated an animal model of severe malnutrition with and without low-grade inflammation to investigate the effects on glucose homeostasis. Immediately after weaning, rats were fed diets containing 5 [low-protein diet (LP)] or 20% protein [control diet (CTRL)], with or without repeated low-dose intraperitoneal lipopolysaccharide (LPS; 2 mg/kg), to mimic inflammation resulting from infections. After 4 wk on the diets, hyperglycemic clamps or euglycemic hyper-insulinemic clamps were performed with infusion of [U-13C6] glucose and [2-C-13] glycerol to assess insulin secretion, action, and hepatic glucose metabolism. In separate studies, pancreatic islets were isolated for further analyses of insulin secretion and islet morphometry. Glucose clearance was reduced significantly by LP feeding alone (16%) and by LP feeding with LPS administration (43.8%) compared with control during the hyperglycemic clamps. This was associated with a strongly reduced insulin secretion in LP-fed rats in vivo as well as ex vivo in islets but signficantly enhanced whole body insulin sensitivity. Gluconeogenesis rates were unaffected by LP feeding, but glycogenolysis was higher after LP feeding. A protein-deficient diet in young rats leads to a susceptibility to low-dose endotoxin-induced impairment in glucose clearance with a decrease in the islet insulin secretory pathway. A protein-deficient diet is associated with enhanced peripheral insulin sensitivity but impaired insulin-mediated suppression of hepatic glycogenolysis.

    Original languageEnglish
    Pages (from-to)E466-E473
    Number of pages8
    JournalAmerican Journal of Physiology - Endocrinology and Metabolism
    Volume309
    Issue number5
    DOIs
    Publication statusPublished - 1-Sep-2015

    Keywords

    • malnutrition
    • stable isotopes
    • insulin
    • glycemic clamps
    • oxidative stress
    • BETA-CELL DYSFUNCTION
    • SEVERELY MALNOURISHED CHILDREN
    • INSULIN-SECRETION
    • CALORIE MALNUTRITION
    • ENERGY MALNUTRITION
    • IN-VIVO
    • CARBOHYDRATE-METABOLISM
    • PROLONGED ELEVATION
    • OXIDATIVE STRESS
    • LIMITED PERIOD

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