title: Intranasal insulin decreases circulating cortisol concentrations during early sleep in elderly humans.
abstract: Aging is associated with increases in hypothalamic-pituitary-adrenal (HPA) axis activity that can predispose to metabolic and cognitive impairments. We investigated in elderly and young subjects whether intranasal insulin administration to the human brain reduces early-sleep nadir concentrations of adrenocorticotropin and cortisol, that is, indicators of baseline HPA axis activity. In within-subject comparisons, intranasal insulin (160 IU) or placebo was administered to 14 elderly (mean age 70.0 years) and 30 young (23.6 years) healthy subjects before bedtime. Sleep was polysomnographically assessed and blood samples were repeatedly collected. Elderly compared with young participants displayed increased early-sleep cortisol concentrations (p < 0.04) and reductions in slow wave and REM sleep (p < 0.001). Insulin administration reduced cortisol levels between 2300 hours and 0020 hours in the elderly (p = 0.03) but not young participants (p = 0.56; p = 0.003 for interaction). Findings indicate that central nervous insulin acts as an inhibitory signal in basal HPA axis activity regulation and suggest that intranasal insulin may normalize sleep-associated stress axis activity in older age.
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Thienel
authors.affiliation: Child Development Center, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Ines
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Benedict
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (IDM), Tübingen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.affiliation: Institute of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen (IDM), Tübingen, Germany. Electronic address: manfred.hallschmid@uni-tuebingen.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hallschmid
mesh_terms: D000281:Administration, Intranasal; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D055815:Young Adult
chemical_list: D007328:Insulin; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: Aging; Brain; Cortisol; Hypothalamic-pituitary-adrenal axis; Insulin; Sleep