Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30074
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dc.contributor.authorRajapaksha, Indu G-
dc.contributor.authorGunarathne, Lakmie S-
dc.contributor.authorAsadi, Khashayar-
dc.contributor.authorLaybutt, Ross-
dc.contributor.authorAndrikopoulous, Sof-
dc.contributor.authorAlexander, Ian E-
dc.contributor.authorWatt, Mathew J-
dc.contributor.authorAngus, Peter W-
dc.contributor.authorHerath, Chandana B-
dc.date2021-12-23-
dc.date.accessioned2022-06-22T06:51:31Z-
dc.date.available2022-06-22T06:51:31Z-
dc.date.issued2022-05-
dc.identifier.citationHepatology Communications 2022; 6(5): 1056-1072en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/30074-
dc.description.abstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is frequently associated with type 2 diabetes. However, there is no specific medical therapy to treat this condition. Angiotensin-converting enzyme 2 (ACE2) of the protective renin angiotensin system generates the antifibrotic peptide angiotensin-(1-7) from profibrotic angiotensin II peptide. In this study, we investigated the therapeutic potential of ACE2 in diabetic NAFLD mice fed a high-fat (20%), high-cholesterol (2%) diet for 40 weeks. Mice were given a single intraperitoneal injection of ACE2 using an adeno-associated viral vector at 30 weeks of high-fat, high-cholesterol diet (15 weeks after induction of diabetes) and sacrificed 10 weeks later. ACE2 significantly reduced liver injury and fibrosis in diabetic NAFLD mice compared with the control vector injected mice. This was accompanied by reductions in proinflammatory cytokine expressions, hepatic stellate cell activation, and collagen 1 expression. Moreover, ACE2 therapy significantly increased islet numbers, leading to an increased insulin protein content in β-cells and plasma insulin levels with subsequent reduction in plasma glucose levels compared with controls. Conclusion: We conclude that ACE2 gene therapy reduces liver fibrosis and hyperglycemia in diabetic NAFLD mice and has potential as a therapy for patients with NAFLD with diabetes.en
dc.language.isoeng-
dc.titleAngiotensin Converting Enzyme-2 Therapy Improves Liver Fibrosis and Glycemic Control in Diabetic Mice With Fatty Liver.en
dc.typeJournal Articleen
dc.identifier.journaltitleHepatology Communicationsen
dc.identifier.affiliationAnatomical Pathologyen
dc.identifier.affiliationGastroenterology and Hepatologyen
dc.identifier.affiliationMedicine (University of Melbourne)en
dc.identifier.affiliationSchool of Medicine, University of Sydney, Children's Medical Research Institute, Sydney, NSW, Australiaen
dc.identifier.affiliationSouth Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australiaen
dc.identifier.affiliationDepartment Anatomy and Physiology, The University of Melbourne, Melbourne, VIC, Australiaen
dc.identifier.affiliationGarvan Institute of Medical Research, Sydney, NSW, Australiaen
dc.identifier.affiliationSt. Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australiaen
dc.identifier.affiliationIngham Institute for Applied Medical Research, Liverpool, NSW, Australiaen
dc.identifier.pubmedurihttps://pubmed.ncbi.nlm.nih.gov/34951153/en
dc.identifier.doi10.1002/hep4.1884en
dc.type.contentTexten
dc.identifier.orcid0000-0002-3326-3654en
dc.identifier.orcid0000-0001-5841-057Xen
dc.identifier.orcid0000-0002-4403-7177en
dc.identifier.orcid0000-0003-3304-1207en
dc.identifier.orcid0000-0002-8932-8592en
dc.identifier.orcid0000-0001-8505-2317en
dc.identifier.orcid0000-0001-9151-8531en
dc.identifier.pubmedid34951153-
local.name.researcherAngus, Peter W
item.cerifentitytypePublications-
item.openairetypeJournal Article-
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
crisitem.author.deptPathology-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
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