Stress-inducible Mig6 promotes pancreatic beta cell destruction in the pathogenesis of diabetes

dc.contributor.advisorFueger, Patrick T.
dc.contributor.authorChen, Yi-Chun
dc.contributor.otherDay, Richard N.
dc.contributor.otherElmendorf, Jeffrey S.
dc.date.accessioned2015-04-22T16:40:24Z
dc.date.available2015-04-22T16:40:24Z
dc.date.issued2014-12-08
dc.degree.date2014en_US
dc.degree.disciplineDepartment of Cellular & Integrative Physiologyen
dc.degree.grantorIndiana Universityen_US
dc.degree.levelPh.D.en_US
dc.descriptionIndiana University-Purdue University Indianapolis (IUPUI)en_US
dc.description.abstractPancreatic insulin-secreting beta cell failure is central to the development of diabetes. Therapeutic applications targeted at understanding and manipulating beta cell destruction mechanisms should enhance the preservation of functional beta cell mass and prevent diabetes. To this end, we have demonstrated that diabetogenic assaults (e.g., endoplasmic reticulum stress, glucolipotoxicity, and pro-inflammatory cytokines) attenuate the activation of beta cell pro-survival signaling pathways via a stress-inducible molecule called Mitogen-inducible gene 6 (Mig6). We discovered that the overabundance of Mig6 exacerbates stress-induced beta cell apoptosis and inhibits insulin secretion. Conversely, the deficiency of Mig6 partially protected beta cells from DNA damage-induced cell death. Further, we established that Mig6 haploinsufficient mice retained islet integrity and function and exhibited greater beta cell mass recovery following treatment with multiple low doses of the beta cell toxin streptozotocin. These data suggest that Mig6 may be a therapeutic target for beta cell preservation in diabetes.en_US
dc.identifier.urihttps://hdl.handle.net/1805/6226
dc.identifier.urihttp://dx.doi.org/10.7912/C2/2003
dc.subjectDiabetesen_US
dc.subjectPancreatic beta cellsen_US
dc.subjectEGFRen_US
dc.subjectMig6en_US
dc.subject.lcshPancreatic beta cells -- Preservationen_US
dc.subject.lcshPancreatic beta cellsen_US
dc.subject.lcshDiabetes -- Developmenten_US
dc.subject.lcshStreptozotocinen_US
dc.subject.lcshApoptosisen_US
dc.subject.lcshMitogensen_US
dc.subject.lcshDiabetesen_US
dc.subject.lcshDiabetes -- Researchen_US
dc.subject.lcshTransgenic mice -- Researchen_US
dc.titleStress-inducible Mig6 promotes pancreatic beta cell destruction in the pathogenesis of diabetesen_US
dc.typeThesisen
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