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dc.contributor.authorMeakin, Paul Jen_UK
dc.contributor.authorHarper, Alex Jen_UK
dc.contributor.authorHamilton, David Leeen_UK
dc.contributor.authorGallagher, Jenniferen_UK
dc.contributor.authorMcNeilly, Alison Den_UK
dc.contributor.authorBurgess, Laura Aen_UK
dc.contributor.authorVaanholt, Lobke Men_UK
dc.contributor.authorBannon, Kirsten Aen_UK
dc.contributor.authorLatcham, Judyen_UK
dc.contributor.authorHussain, Ishruten_UK
dc.contributor.authorSpeakman, John Ren_UK
dc.contributor.authorHowlett, David Ren_UK
dc.contributor.authorAshford, Michael L Jen_UK
dc.description.abstractInsulin resistance and impaired glucose homoeostasis are important indicators of Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An essential feature of AD pathology is the presence of BACE1 (beta-site amyloid precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid peptides. However, whether BACE1 also plays a role in glucose homoeostasis is presently unknown. We have used transgenic mice to analyse the effects of loss of BACE1 on body weight, and lipid and glucose homoeostasis. BACE1-/- mice are lean, with decreased adiposity, higher energy expenditure, and improved glucose disposal and peripheral insulin sensitivity than wild-type littermates. BACE1-/- mice are also protected from diet-induced obesity. BACE1-deficient skeletal muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity. The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein 1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle, indicative of increased uncoupled respiration and metabolic inefficiency. Thus BACE1 levels may play a critical role in glucose and lipid homoeostasis in conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1 activity may be important novel approaches for the treatment of diabetes.en_UK
dc.publisherPortland Press for the Biochemical Societyen_UK
dc.relationMeakin PJ, Harper AJ, Hamilton DL, Gallagher J, McNeilly AD, Burgess LA, Vaanholt LM, Bannon KA, Latcham J, Hussain I, Speakman JR, Howlett DR & Ashford MLJ (2012) Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice. Biochemical Journal, 441 (1), pp. 285-296.
dc.rightsThe publisher does not allow this work to be made publicly available in this Repository. Please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study.en_UK
dc.subjectbeta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)en_UK
dc.subjectglucose uptakeen_UK
dc.subjectinsulin sensitivityen_UK
dc.subjectskeletal muscleen_UK
dc.subjectuncoupling protein (UCP)en_UK
dc.subjectEvidence-Based Medicineen_UK
dc.subjectDiabetes Mellitus, Type 2 therapyen_UK
dc.titleReduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in miceen_UK
dc.typeJournal Articleen_UK
dc.rights.embargoreason[Hamilton_2012_Reduction_in_BACE1.pdf] The publisher does not allow this work to be made publicly available in this Repository therefore there is an embargo on the full text of the work.en_UK
dc.citation.jtitleBiochemical Journalen_UK
dc.type.statusVoR - Version of Recorden_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationUniversity of Aberdeenen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
dc.contributor.affiliationUniversity of Aberdeenen_UK
dc.contributor.affiliationUniversity of Dundeeen_UK
rioxxterms.typeJournal Article/Reviewen_UK
local.rioxx.authorMeakin, Paul J|en_UK
local.rioxx.authorHarper, Alex J|en_UK
local.rioxx.authorHamilton, David Lee|0000-0002-5620-4788en_UK
local.rioxx.authorGallagher, Jennifer|en_UK
local.rioxx.authorMcNeilly, Alison D|en_UK
local.rioxx.authorBurgess, Laura A|en_UK
local.rioxx.authorVaanholt, Lobke M|en_UK
local.rioxx.authorBannon, Kirsten A|en_UK
local.rioxx.authorLatcham, Judy|en_UK
local.rioxx.authorHussain, Ishrut|en_UK
local.rioxx.authorSpeakman, John R|en_UK
local.rioxx.authorHowlett, David R|en_UK
local.rioxx.authorAshford, Michael L J|en_UK
local.rioxx.projectInternal Project|University of Stirling|
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles

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