Persistent Link:
http://hdl.handle.net/10150/195657
Title:
Diabetic Kidney Disease in the VCD Model of Menopause
Author:
Diamond-Stanic, Maggie Keck
Issue Date:
2008
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Kidney disease is a major complication of diabetes and accounts for one-third of all diabetes-related deaths. Estrogen is considered protective against cardiovascular and non-diabetic renal disease, however it is unclear if this protection extends to diabetes and diabetic kidney disease.To address these questions, we have used a new model of menopause in which repeated daily injections of 4-vinylcyclohexene (VCD) induces gradual ovarian failure in mice. Unlike with ovariectomy, the VCD model preserves the gradual transition into ovarian failure (OF) (modeling perimenopause). Also, following OF, the residual ovarian tissue is retained and secretes androgens, similar to the androgen production by postmenopausal human ovaries.The VCD model of menopause was combined with the streptozotocin (STZ) model of type 1 diabetes, and the development of diabetes and diabetic kidney damage were studied over the subsequent 6 weeks. We observed that blood glucose levels are higher in post-OF diabetic mice compared to cycling diabetic and peri-OF diabetic mice. Renal cell proliferation, an early marker of kidney damage, is increased in post-OF diabetic mice compared to cycling diabetic mice, as measured by expression of proliferating cell nuclear antigen. We also demonstrate that expression of α-smooth muscle actin is increased in post-OF diabetic mice compared to cycling diabetic mice. Five weeks after STZ injection, post-OF diabetic mice had higher rates of urine albumin excretion than cycling diabetic mice.Using real-time PCR, we identified changes in expression between post-OF diabetic and cycling diabetic mice of genes which have previously been associated with diabetic kidney damage. We also show that some of these changes occur in peri-OF diabetic mice as well. Using microarray, we identified 119 new genes which are regulated by the combination of ovarian failure and diabetes in the mouse kidney.These data support our hypothesis that the changes in hormones which occur during the transition into ovarian failure exacerbate the development and progression of diabetic kidney damage in mice. These data also highlight the utility and importance of the VCD model of menopause in the study of diabetic kidney damage.
Type:
text; Electronic Dissertation
Keywords:
diabetes; kidney; menopause; STZ; VCD; ovarian failure
Degree Name:
PhD
Degree Level:
doctoral
Degree Program:
Physiological Sciences; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Brooks, Heddwen L
Committee Chair:
Brooks, Heddwen L

Full metadata record

DC FieldValue Language
dc.language.isoENen_US
dc.titleDiabetic Kidney Disease in the VCD Model of Menopauseen_US
dc.creatorDiamond-Stanic, Maggie Kecken_US
dc.contributor.authorDiamond-Stanic, Maggie Kecken_US
dc.date.issued2008en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractKidney disease is a major complication of diabetes and accounts for one-third of all diabetes-related deaths. Estrogen is considered protective against cardiovascular and non-diabetic renal disease, however it is unclear if this protection extends to diabetes and diabetic kidney disease.To address these questions, we have used a new model of menopause in which repeated daily injections of 4-vinylcyclohexene (VCD) induces gradual ovarian failure in mice. Unlike with ovariectomy, the VCD model preserves the gradual transition into ovarian failure (OF) (modeling perimenopause). Also, following OF, the residual ovarian tissue is retained and secretes androgens, similar to the androgen production by postmenopausal human ovaries.The VCD model of menopause was combined with the streptozotocin (STZ) model of type 1 diabetes, and the development of diabetes and diabetic kidney damage were studied over the subsequent 6 weeks. We observed that blood glucose levels are higher in post-OF diabetic mice compared to cycling diabetic and peri-OF diabetic mice. Renal cell proliferation, an early marker of kidney damage, is increased in post-OF diabetic mice compared to cycling diabetic mice, as measured by expression of proliferating cell nuclear antigen. We also demonstrate that expression of α-smooth muscle actin is increased in post-OF diabetic mice compared to cycling diabetic mice. Five weeks after STZ injection, post-OF diabetic mice had higher rates of urine albumin excretion than cycling diabetic mice.Using real-time PCR, we identified changes in expression between post-OF diabetic and cycling diabetic mice of genes which have previously been associated with diabetic kidney damage. We also show that some of these changes occur in peri-OF diabetic mice as well. Using microarray, we identified 119 new genes which are regulated by the combination of ovarian failure and diabetes in the mouse kidney.These data support our hypothesis that the changes in hormones which occur during the transition into ovarian failure exacerbate the development and progression of diabetic kidney damage in mice. These data also highlight the utility and importance of the VCD model of menopause in the study of diabetic kidney damage.en_US
dc.typetexten_US
dc.typeElectronic Dissertationen_US
dc.subjectdiabetesen_US
dc.subjectkidneyen_US
dc.subjectmenopauseen_US
dc.subjectSTZen_US
dc.subjectVCDen_US
dc.subjectovarian failureen_US
thesis.degree.namePhDen_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplinePhysiological Sciencesen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBrooks, Heddwen Len_US
dc.contributor.chairBrooks, Heddwen Len_US
dc.contributor.committeememberHenriksen, Erik J.en_US
dc.contributor.committeememberHoyer, Patricia B.en_US
dc.contributor.committeememberLynch, Ronald M.en_US
dc.contributor.committeememberStamer, William D.en_US
dc.identifier.proquest2820en_US
dc.identifier.oclc659749882en_US
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