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Protective effect of endothelial nitric oxide synthase against induction of chemically-induced diabetes in mice

Zhang, Jianhong (Annette); Kawashima, Seinosuke; Yokoyama, M; Huang, P; Hill, Caryl

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Since activation of endothelial nitric oxide synthase has been shown to exert protective effects against the metabolic syndrome, while endothelial nitric oxide synthase knockout mice develop hyperinsulinemia and glucose intolerance, we hypothesised that endothelial nitric oxide might play a protective role against induction of diabetes. The role of endothelial nitric oxide in the development of chemically-induced diabetes has been determined using mice in which the bioavailability of...[Show more]

dc.contributor.authorZhang, Jianhong (Annette)
dc.contributor.authorKawashima, Seinosuke
dc.contributor.authorYokoyama, M
dc.contributor.authorHuang, P
dc.contributor.authorHill, Caryl
dc.date.accessioned2015-12-08T22:17:43Z
dc.identifier.issn1089-8603
dc.identifier.urihttp://hdl.handle.net/1885/31026
dc.description.abstractSince activation of endothelial nitric oxide synthase has been shown to exert protective effects against the metabolic syndrome, while endothelial nitric oxide synthase knockout mice develop hyperinsulinemia and glucose intolerance, we hypothesised that endothelial nitric oxide might play a protective role against induction of diabetes. The role of endothelial nitric oxide in the development of chemically-induced diabetes has been determined using mice in which the bioavailability of endothelial nitric oxide was either increased, through upregulation of endothelial nitric oxide synthase, or absent, through deletion of endothelial nitric oxide synthase gene. Diabetes was induced intraperitoneally with either a single dose of alloxan, streptozotocin, or multiple low doses of streptozotocin and blood glucose monitored twice a week. The role of cyclic guanosine monophosphate was investigated in wildtype mice by treatment with the phosphodiesterase inhibitor, tadalafil, during diabetes induction. Results showed that the incidence of diabetes was markedly decreased in mice overexpressing endothelial nitric oxide synthase, compared to wildtype or endothelial nitric oxide synthase knockout mice, regardless of the method of diabetes induction. Under normal physiological conditions, or during diabetes induction with alloxan or multiple low doses of streptozotocin, blood glucose was significantly lower in mice overexpressing endothelial nitric oxide synthase compared to wildtype or knockout mice. Treatment with tadalafil had no effect on the incidence or severity of diabetes in wildtype mice. We conclude that upregulation of endothelial nitric oxide synthase exerts a protective action against diabetes induction through a direct effect of nitric oxide, independently of cyclic guanosine monophosphate.
dc.publisherAcademic Press
dc.sourceNitric Oxide - Biology and Chemistry
dc.subjectKeywords: alloxan; cyclic GMP; endothelial nitric oxide synthase; streptozocin; tadalafil; alloxan diabetes mellitus; animal model; article; blood glucose monitoring; controlled study; drug effect; male; morbidity; nonhuman; priority journal; streptozocin diabetes; Alloxan; eNOS overexpression; Streptozotocin; Type I diabetes
dc.titleProtective effect of endothelial nitric oxide synthase against induction of chemically-induced diabetes in mice
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume17
dc.date.issued2007
local.identifier.absfor060602 - Animal Physiology - Cell
local.identifier.ariespublicationu4321547xPUB79
local.type.statusPublished Version
local.contributor.affiliationZhang, Jianhong (Annette), College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKawashima, Seinosuke, Kobe University
local.contributor.affiliationYokoyama, M, Kobe University
local.contributor.affiliationHuang, P, Harvard Medical School
local.contributor.affiliationHill, Caryl, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage69
local.bibliographicCitation.lastpage74
local.identifier.doi10.1016/j.niox.2007.06.001
local.identifier.absseo920103 - Cardiovascular System and Diseases
dc.date.updated2015-12-08T08:09:55Z
local.identifier.scopusID2-s2.0-34547894200
CollectionsANU Research Publications

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