title: Chronic peripheral hyperinsulinemia has no substantial influence on tau phosphorylation in vivo.
abstract: Chronic peripheral hyperinsulinemia is one of the main characteristics of type 2 diabetes accompanied by impaired glucose homeostasis and obesity resulting from increased food intake and decreased physical activity. Patients with type 2 diabetes have a higher risk of cognitive decline and neurodegenerative diseases e.g. Alzheimer's disease (AD). Furthermore, obesity or hyperinsulinemia alone already increase the probability of cognitive decline possibly progressing to AD. Tau hyperphosphorylation is one of the pathological hallmarks of AD and so called tauopathies. Aim of the present study was to analyze the influence of obesity-associated hyperinsulinemia on tau phosphorylation without changes in glucose homeostasis. 15% high fat diet fed over 12-16 weeks induced 2.4-fold increased plasma insulin levels without changing glucose tolerance. However, this diet did not lead to substantial differences in tau phosphorylation in the brain of C57Bl/6 mice. Additionally, chronic hyperinsulinemia did not influence downstream insulin receptor signaling and the expression of the tau kinases (e.g. ERK-1/-2, Akt, GSK-3β, CDK5 or JNK) and tau phosphatases (e.g. PP2A) in the murine central nervous system. Thus, we successfully induced hyperinsulinemia without causing glucose intolerance in our experimental animals but this did not influence central insulin receptor signaling or tau phosphorylation.
authors.affiliation: Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Becker
authors.forename: Susanna
authors.initials: S
authors.lastname: Freude
authors.forename: Johanna
authors.initials: J
authors.lastname: Zemva
authors.forename: Oliver
authors.initials: O
authors.lastname: Stöhr
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krone
authors.forename: Markus
authors.initials: M
authors.lastname: Schubert
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002908:Chronic Disease; D059305:Diet, High-Fat / Q000009:adverse effects; D006946:Hyperinsulinism / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins