Show simple item record

dc.contributor.authorZhao, Zeping
dc.date.accessioned2018-10-23T13:33:14Z
dc.date.available2019-08-22T06:00:40Z
dc.date.issued2018-08-30
dc.identifier.otherZhao_cornellgrad_0058F_11041
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:11041
dc.identifier.otherbibid: 10489639
dc.identifier.urihttps://hdl.handle.net/1813/59543
dc.description.abstractInflammation is a well-accepted cause of insulin resistance (IR), and anti-inflammatory treatments (AITs) are supposed to improve insulin sensitivity. Herein, we revealed that knockout of a potent anti-inflammatory protein: murine regenerating islet-derived protein 3β (REG3β), paradoxically enhanced insulin sensitivity, and completely blocked development of IR induced by lipopolysaccharide (LPS) or dextran sulfate sodium (DSS)-mediated inflammation in mice. These knockout effects were reversed by exogenous REG3β administration, and conferred by ablating two previously-unknown bindings of REG3β to transmembrane proteins exostosin-like glycosyltransferase 3 (EXTL3) that suppressed expression of insulin receptor (INSR) and protein kinase B (AKT) and cytokine receptor C-X-C motif chemokine receptor 4 (CXCR4) that inhibited phosphorylation of INSR and AKT. Prior conflicting effects of anti-inflammatory drugs on insulin sensitivity could now be explained by their different ability to alter tissue REG3β protein. Suggested human homologue regenerating islet-derived protein 3α (hREG3α) exhibited similar functions to those of REG3β. Our work unveiled REG3β as a potent negative determinant of insulin sensitivity and an essential mediator for inflammation to induce IR. These findings drastically revise current theory on the relationship of inflammation and IR, and offer an exciting new therapy target of IR and a safer, alternative prospect to treat inflammation in diabetes.
dc.language.isoen_US
dc.subjectanti-inflammation
dc.subjectInsulin resistance
dc.subjectREG3β
dc.subjectInflammation
dc.subjectGenetics
dc.subjectMolecular biology
dc.subjectNutrition
dc.titleInflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance
dc.typedissertation or thesis
thesis.degree.disciplineAnimal Science
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Animal Science
dc.contributor.chairLei, Xingen
dc.contributor.committeeMemberBrown, William J.
dc.contributor.committeeMemberGu, Zhenglong
dc.contributor.committeeMemberSevier, Carolyn S.
dcterms.licensehttps://hdl.handle.net/1813/59810
dc.identifier.doihttps://doi.org/10.7298/X4K072G9


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Statistics