The effects of diet varying in fat content on the pathogenesis of diabetes mellitus in wistar rat offspring

dc.contributor.advisorGrobbelaar, C.W. (Craig)en
dc.contributor.coadvisorCerf, M.E.en
dc.contributor.emailnhlanhlasimphiwe@gmail.comen
dc.contributor.postgraduateMthembu, Nhlanhla Simphiwe Christaen
dc.date.accessioned2016-06-10T07:03:50Z
dc.date.available2016-06-10T07:03:50Z
dc.date.created2016-04-22en
dc.date.issued2015en
dc.descriptionDissertation (MSc)--University of Pretoria, 2015.en
dc.description.abstractAims/hypothesis: The incidence of type 2 diabetes (T2D) is increasing globally. T2D is characterised by progressive deterioration of glycaemic control. These changes in glucose homeostasis are primarily due to ?-cell secretory dysfunction and/or peripheral insulin resistance. Studies show that maternal health directly influences foetal development and birth outcomes. Malnutrition of the growing foetus may lead to development of T2D and other metabolic diseases later in life. Consequently, several studies have reported that maternal diet programmes the foetus leading to altered physiology and metabolism in the offspring. Foetal programming refers to the exposure to a stimulus and/or insult during the critical periods of development i.e. foetal and early neonatal life. We therefore sought to ascertain how a dietary fat content in maternal diet affects foetal programming and its contribution to the pathogenesis of T2D of the offspring. Methods: Pregnant rats were randomly grouped and maintained on diets varying in fat content: 10% (Control), 20% (20F), 30% (30F) and 40% (40F) fat throughout their pregnancy. Pancreata were collected and quantitative polymerase chain reaction tests were performed to determine the mRNA expression profiles of the insulin signaling and transcription factors including Pdx1, MafB, IR?, insulin and glucagon. Other pancreata were immunostained followed by image analysis of these factors. Results: In 40F neonates, Ins1, Ins2, glucagon, MafB and IRS2 mRNA expression was reduced. Further, in 30F neonates, Ins1, Pdx1 and MafB mRNA expression was reduced. There were no changes in immunoreactivity for the factors studied. However, when separating the offspring according to gender, IR? immunoreactivity was reduced in 40F females compared to 40F males. Conclusion: Continuous exposure of pregnant rats to an excessively high fat diet impairs gene expression of key factors involved in insulin signaling and islet development in their neonatal offspring. This reflects foetal programming of metabolic pathways in insulin signaling and ?-cell development and function which potentially renders these offspring susceptible to metabolic disease and the development of T2D.en
dc.description.availabilityUnrestricteden
dc.description.degreeMScen
dc.description.departmentPhysiologyen
dc.identifier.citationMthembu, NSC 2015, The effects of diet varying in fat content on the pathogenesis of diabetes mellitus in wistar rat offspring, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/53032>en
dc.identifier.otherA2016en
dc.identifier.urihttp://hdl.handle.net/2263/53032
dc.language.isoenen
dc.publisherUniversity of Pretoriaen_ZA
dc.rights© 2016 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria.en
dc.subjectUCTDen
dc.titleThe effects of diet varying in fat content on the pathogenesis of diabetes mellitus in wistar rat offspringen
dc.typeDissertationen

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