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dc.contributor.authorOsundiji, Mayowa A
dc.contributor.authorLam, Daniel D
dc.contributor.authorShaw, Jill
dc.contributor.authorYueh, Chen-Yu
dc.contributor.authorMarkkula, S Pauliina
dc.contributor.authorHurst, Paul
dc.contributor.authorColliva, Carolina
dc.contributor.authorRoda, Aldo
dc.contributor.authorHeisler, Lora K
dc.contributor.authorEvans, Mark L
dc.date.accessioned2018-12-01T00:30:16Z
dc.date.available2018-12-01T00:30:16Z
dc.date.issued2012-02
dc.identifier.issn0012-1797
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286183
dc.description.abstractAs patients decline from health to type 2 diabetes, glucose-stimulated insulin secretion (GSIS) typically becomes impaired. Although GSIS is driven predominantly by direct sensing of a rise in blood glucose by pancreatic β-cells, there is growing evidence that hypothalamic neurons control other aspects of peripheral glucose metabolism. Here we investigated the role of the brain in the modulation of GSIS. To examine the effects of increasing or decreasing hypothalamic glucose sensing on glucose tolerance and insulin secretion, glucose or inhibitors of glucokinase, respectively, were infused into the third ventricle during intravenous glucose tolerance tests (IVGTTs). Glucose-infused rats displayed improved glucose handling, particularly within the first few minutes of the IVGTT, with a significantly lower area under the excursion curve within the first 10 min (AUC0-10). This was explained by increased insulin secretion. In contrast, infusion of the glucokinase inhibitors glucosamine or mannoheptulose worsened glucose tolerance and decreased GSIS in the first few minutes of IVGTT. Our data suggest a role for brain glucose sensors in the regulation of GSIS, particularly during the early phase. We propose that pharmacological agents targeting hypothalamic glucose-sensing pathways may represent novel therapeutic strategies for enhancing early phase insulin secretion in type 2 diabetes.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Diabetes Association
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectPancreas
dc.subjectHypothalamus
dc.subjectAnimals
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectInsulin
dc.subjectGlucokinase
dc.subjectMannoheptulose
dc.subjectGlucose
dc.subjectGlucose Tolerance Test
dc.subjectInjections, Intraventricular
dc.subjectMale
dc.subjectInsulin Secretion
dc.titleBrain glucose sensors play a significant role in the regulation of pancreatic glucose-stimulated insulin secretion.
dc.typeArticle
prism.endingPage328
prism.issueIdentifier2
prism.publicationDate2012
prism.publicationNameDiabetes
prism.startingPage321
prism.volume61
dc.identifier.doi10.17863/CAM.33495
rioxxterms.versionofrecord10.2337/db11-1050
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2012-02
dc.contributor.orcidEvans, Mark [0000-0001-8122-8987]
dc.identifier.eissn1939-327X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Institute of Diabetes and Digestive and Kidney Diseases (R01DK065171)
pubs.funder-project-idMedical Research Council (G0600717)
pubs.funder-project-idJuvenile Diabetes Research Foundation Ltd (JDRF) (1-2006-29)
pubs.funder-project-idWellcome Trust (081713/Z/06/Z)
pubs.funder-project-idJuvenile Diabetes Research Foundation Ltd (JDRF) (1-2003-78)
cam.issuedOnline2011-12-30


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International