Please use this identifier to cite or link to this item:
Scopus Web of Science® Altmetric
Full metadata record
DC FieldValueLanguage
dc.contributor.authorGatford, K.-
dc.contributor.authorDe Blasio, M.-
dc.contributor.authorHow, T.-
dc.contributor.authorHarland, M.-
dc.contributor.authorPearce, B.-
dc.contributor.authorOwens, J.-
dc.identifier.citationExperimental Physiology, 2012; 97(5):663-675-
dc.description.abstractPlasticity of insulin secretion is essential to maintain the action of insulin during insulin resistance and to prevent diabetes. Investigation of the plasticity of insulin secretion and its regulation is challenging, and the objective of this study was to develop a novel large-animal-based model. The effect of chronic moderate hyperglycaemia on the plasticity of insulin secretion, β-cell mass and function was determined in sheep. Adolescent sheep (120 days old) were infused with 25% glucose for 16 days to increase blood glucose by 50% (n = 10), and control animals (n = 9) were infused with saline. Glucose- and arginine-stimulated insulin secretion, insulin sensitivity and glucose effectiveness were measured in vivo before and during treatment (days 10–14), and β-cell mass was measured at the end of treatment. Hyperglycaemia increased blood glucose (+53%) and plasma insulin (+403%; each P < 0.003) and did not alter whole-body insulin sensitivity. Hyperglycaemia increased glucose-stimulated insulin secretion (particularly second phase; five-fold) and arginine-stimulated insulin secretion (particularly first phase; four-fold). Hyperglycaemia reduced β-cell mass (∼50%, P = 0.038) and increased glucose- and arginine-stimulated insulin secretion relative to β-cell mass five-fold (P = 0.060) and 20-fold (P = 0.007), respectively. Chronic hyperglycaemia therefore induces marked adaptation and upregulation of glucose- and arginine-stimulated insulin secretion by enhancing β-cell function rather than increasing β-cell mass in the sheep, consistent with long-term adaptations seen in humans. This marked plasticity of insulin secretion in response to moderate hyperglycaemia provides a novel model for the investigation of factors affecting its capacity and underlying determinants.-
dc.description.statementofresponsibilityKathryn L. Gatford, Miles J. De Blasio, Tasma A. How, M. Lyn Harland, Brooke L. Summers-Pearce and Julie A. Owens-
dc.publisherBlackwell Publishing Ltd-
dc.rights© 2012 The Authors. Experimental Physiology © 2012 The Physiological Society-
dc.subjectSheep, Domestic-
dc.subjectInsulin Resistance-
dc.subjectBlood Glucose-
dc.subjectGlucose Tolerance Test-
dc.subjectAdaptation, Physiological-
dc.subjectInsulin-Secreting Cells-
dc.subjectInsulin Secretion-
dc.titleTesting the plasticity of insulin secretion and β-cell function in vivo: responses to chronic hyperglycaemia in the sheep-
dc.title.alternativeTesting the plasticity of insulin secretion and beta-cell function in vivo: responses to chronic hyperglycaemia in the sheep-
dc.typeJournal article-
dc.identifier.orcidGatford, K. [0000-0002-2823-3004]-
dc.identifier.orcidOwens, J. [0000-0002-7498-1353]-
Appears in Collections:Aurora harvest 5
Obstetrics and Gynaecology publications

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.