title: Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions.
abstract: OBJECTIVE
  Impaired insulin sensitivity is a major factor leading to type 2 diabetes. Animal studies suggest that the brain is involved in the regulation of insulin sensitivity. We investigated whether insulin action in the human brain regulates peripheral insulin sensitivity and examined which brain areas are involved.
  
  
  METHODS
  Insulin and placebo were given intranasally. Plasma glucose, insulin and C-peptide were measured in 103 participants at 0, 30 and 60 min. A subgroup (n = 12) was also studied with functional MRI, and blood sampling at 0, 30 and 120 min. For each time-point, the HOMA of insulin resistance (HOMA-IR) was calculated as an inverse estimate of peripheral insulin sensitivity.
  
  
  RESULTS
  Plasma insulin increased and subsequently decreased. This excursion was accompanied by slightly decreased plasma glucose, resulting in an initially increased HOMA-IR. At 1 h after insulin spray, the HOMA-IR subsequently decreased and remained lower up to 120 min. An increase in hypothalamic activity was observed, which correlated with the increased HOMA-IR at 30 min post-spray. Activity in the putamen, right insula and orbitofrontal cortex correlated with the decreased HOMA-IR at 120 min post-spray.
  
  
  CONCLUSIONS
  Central insulin action in specific brain areas, including the hypothalamus, may time-dependently regulate peripheral insulin sensitivity. This introduces a potential novel mechanism for the regulation of peripheral insulin sensitivity and underlines the importance of cerebral insulin action for the whole organism.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Eberhard Karls University Tübingen, Otfried-Müller-Str 10, 72076 Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Heni
authors.forename: S
authors.initials: S
authors.lastname: Kullmann
authors.forename: C
authors.initials: C
authors.lastname: Ketterer
authors.forename: M
authors.initials: M
authors.lastname: Guthoff
authors.forename: K
authors.initials: K
authors.lastname: Linder
authors.forename: R
authors.initials: R
authors.lastname: Wagner
authors.forename: K T
authors.initials: KT
authors.lastname: Stingl
authors.forename: R
authors.initials: R
authors.lastname: Veit
authors.forename: H
authors.initials: H
authors.lastname: Staiger
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.forename: H
authors.initials: H
authors.lastname: Preissl
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged
chemical_list: D007328:Insulin