title: Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.
abstract: Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.
authors.affiliation: Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, Department of Internal Medicine, Eberhard Karls University, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heni
authors.forename: Patricia
authors.initials: P
authors.lastname: Schöpfer
authors.forename: Andreas
authors.initials: A
authors.lastname: Peter
authors.forename: Tina
authors.initials: T
authors.lastname: Sartorius
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Matthis
authors.initials: M
authors.lastname: Synofzik
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.forename: Walter
authors.initials: W
authors.lastname: Maetzler
authors.forename: Anita M
authors.initials: AM
authors.lastname: Hennige
mesh_terms: D000328:Adult; D000368:Aged; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin