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Individual differences in glucose homeostasis: do our early life interactions with bacteria matter?
journal contribution
posted on 2006-07-01, 00:00 authored by Frederick R Walker, Julie OwensJulie Owens, Sinan Ali, Deborah M HodgsonExposure to endotoxin during the neonatal period in the rat has been shown to alter the development of the hypothalamic-pituitary-adrenal axis, inducing hyper-responsivity and increased glucocorticoid production in later-life. Glucocorticoids are known to have major metabolic effects, therefore, early life endotoxin exposure may have potentially serious consequences for metabolic homeostasis in the exposed animal. The aims of this study were therefore to assess the effect of neonatal bacterial endotoxin exposure on subsequent glucose homeostasis, insulin action and corticosterone production from puberty through to senescence. Male Fischer-344 rat pups were treated with bacterial endotoxin (0.05 mg/kg Salmonella enteritidis i.p.) or vehicle (sterile pyrogen free saline) on days 3 and 5 postnatally. Insulin and glucose levels were assessed before and during and intraperitoneal glucose tolerance test (IPGTT) together with body mass on postnatal days 40, 80, and 400. In addition, circulating levels of corticosterone were measured at 0, 30, and 90 min following a 30-min restraint challenge at these ages. Neonatal endotoxin challenge did not alter fasting plasma glucose or insulin, but impaired glucose tolerance at puberty (p<.05), improved glucose tolerance in adulthood (p<.05) and had no effect at senescence. During the IPGTT insulin was reduced at all ages (p<.05) following neonatal endotoxin challenge, but insulin sensitivity was unaltered, except for an increase in adulthood (p<.05), which is consistent with the observed improvement in glucose tolerance at this age. Neonatal endotoxin challenge reduced body mass during puberty and senescence (p<.05) but did not alter basal or stressed plasma corticosterone levels at any of the three developmental time points examined. These findings suggest that variations in an individual's early life bacterial environment may contribute to differences in glucose homeostasis, insulin action and disease susceptibility later in life.
History
Journal
Brain, behavior, and immunityVolume
20Issue
4Pagination
401 - 409Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
ISSN
0889-1591Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2006, ElsevierUsage metrics
Categories
Keywords
AgingAnimalsAnimals, NewbornBlood GlucoseCorticosteroneDisease SusceptibilityEndotoxinsGlucose Tolerance TestHomeostasisInsulinMaleRatsRats, Inbred F344Science & TechnologyLife Sciences & BiomedicineImmunologyNeurosciencesPsychiatryNeurosciences & Neurologybacterianeonatepostnatalinfectionglucoseinsulin sensitivityglucose tolerancemetabolismHPANEONATAL ENDOTOXIN EXPOSUREPITUITARY-ADRENAL AXISINSULIN-RESISTANCEMETABOLIC SYNDROMEIMMUNE CHALLENGESOCIAL-BEHAVIORPLASMA-GLUCOSEWISTAR RATSFEMALE RATSGUINEA-PIGImmunology
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