Dissecting long-term glucose metabolism identifies new susceptibility period for metabolic dysfunction in aged mice

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dc.contributor.authorChauhan, Anuradhaen_ZA
dc.contributor.authorWeiss, Heikeen_ZA
dc.contributor.authorKoch, Franziskaen_ZA
dc.contributor.authorIbrahim, Saleh M.en_ZA
dc.contributor.authorVera, Julioen_ZA
dc.contributor.authorWolkenhauer, Olafen_ZA
dc.contributor.authorTiedge, Markusen_ZA
dc.date.accessioned2016-08-18T09:59:09Z
dc.date.available2016-08-18T09:59:09Z
dc.date.issued2015
dc.descriptionCITATION: Chauhan, A., et al. 2015. Dissecting long-term glucose metabolism identifies new susceptibility period for metabolic dysfunction in aged mice. PLoS ONE, 10(11):1-16, doi:10.1371/journal.pone.0140858.
dc.descriptionThe original publication is available at http://journals.plos.org/plosone
dc.description.abstractMetabolic disorders, like diabetes and obesity, are pathogenic outcomes of imbalance in glucose metabolism. Nutrient excess and mitochondrial imbalance are implicated in dysfunctional glucose metabolism with age. We used conplastic mouse strains with defined mitochondrial DNA (mtDNA) mutations on a common nuclear genomic background, and administered a high-fat diet up to 18 months of age. The conplastic mouse strain B6-mtFVB, with a mutation in the mt-Atp8 gene, conferred β-cell dysfunction and impaired glucose tolerance after high-fat diet. To our surprise, despite of this functional deficit, blood glucose levels adapted to perturbations with age. Blood glucose levels were particularly sensitive to perturbations at the early age of 3 to 6 months. Overall the dynamics consisted of a peak between 3–6 months followed by adaptation by 12 months of age. With the help of mathematical modeling we delineate how body weight, insulin and leptin regulate this non-linear blood glucose dynamics. The model predicted a second rise in glucose between 15 and 21 months, which could be experimentally confirmed as a secondary peak. We therefore hypothesize that these two peaks correspond to two sensitive periods of life, where perturbations to the basal metabolism can mark the system for vulnerability to pathologies at later age. Further mathematical modeling may perspectively allow the design of targeted periods for therapeutic interventions and could predict effects on weight loss and insulin levels under conditions of pre-diabetic obesity.en_ZA
dc.description.versionPublisher's versionen_ZA
dc.format.extent16 pagesen_ZA
dc.identifier.citationChauhan, A., et al. 2015. Dissecting long-term glucose metabolism identifies new susceptibility period for metabolic dysfunction in aged mice. PLoS ONE, 10(11):1-16, doi:10.1371/journal.pone.0140858
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0140858
dc.identifier.urihttp://hdl.handle.net/10019.1/99402
dc.language.isoen_ZAen_ZA
dc.publisherPublic Library of Science
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMetabolism -- Disordersen_ZA
dc.subjectDiabetes -- Nutritional aspectsen_ZA
dc.subjectObesityen_ZA
dc.subjectNutritional disorders in old ageen_ZA
dc.subjectGlucose metabolismen_ZA
dc.titleDissecting long-term glucose metabolism identifies new susceptibility period for metabolic dysfunction in aged miceen_ZA
dc.typeArticleen_ZA
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