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Title: | Establishing equivalent diabetes in male and female Nos3-deficient mice results in a comparable onset of diabetic kidney injury. | Authors: | Tesch G.H.;Tian L.;Nikolic-Paterson D.J. | Institution: | (Tian, Nikolic-Paterson, Tesch) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Tian) Department of Nephrology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (Nikolic-Paterson, Tesch) Centre for Inflammatory Diseases, Monash University, Clayton, VIC, Australia | Issue Date: | 25-Nov-2019 | Copyright year: | 2019 | Publisher: | American Physiological Society | Place of publication: | United Kingdom | Publication information: | Physiological Reports. 7 (18) (no pagination), 2019. Article Number: e14197. Date of Publication: 01 Sep 2019. | Abstract: | Clinical studies indicate that sex differences exist in susceptibility for developing diabetic kidney disease (DKD), supporting the need to examine both sexes in animal studies of DKD. Streptozotocin (STZ) is commonly used in male mice to induce diabetes and DKD. However, females are not normally included because their sex hormones partially protect them from STZ-induced islet injury and consequent diabetes. To address this issue, we identified a strategy to induce comparable diabetes in male and female mice using STZ and determined whether both sexes develop equivalent renal injury. Male and female mice lacking the gene for endothelial nitric oxide synthase (Nos3-/-) were made diabetic with five or six low-dose STZ injections, respectively. Groups of male and female mice with equivalent hyperglycemia at week 3 after STZ were assessed for DKD at week 8. STZ-treated male and female Nos3-/- mice maintained comparable hyperglycemia between weeks 3 and 8 had an equivalent increase in HbA1c levels and comparable hypertension. Urine albumin/creatinine levels were elevated eightfold in mice of both sexes at week 8, accompanied by an equivalent loss of podocytes. In diabetic males and females, plasma cystatin C levels and glomerular collagen deposition were similarly increased. Kidney mRNA levels of proinflammatory and profibrotic markers and kidney injury molecule-1 (KIM-1) were equally elevated in males and females, indicating comparable kidney injury. This study shows that equivalent diabetes induces a comparable onset of DKD in male and female Nos3-/- mice, demonstrating that it is possible to include males and females together in studies of DKD.Copyright © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.14814/phy2.14197 | PubMed URL: | 31535473 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31535473] | ISSN: | 2051-817X (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/35880 | Type: | Article | Subjects: | body weight albuminuria animal cell animal experiment animal model animal tissue article blood pressure controlled study enzyme linked immunosorbent assay female glucose blood level hyperglycemia image analysis immunohistochemistry kidney function *kidney injury male moderate renal impairment mouse nonhuman plethysmography real time polymerase chain reaction streptozotocin-induced hyperglycemia systolic blood pressure weight height ratio chlordane/ec [Endogenous Compound] collagen/ec [Endogenous Compound] collagen type 1/ec [Endogenous Compound] collagen type 4/ec [Endogenous Compound] creatinine/ec [Endogenous Compound] cystatin/ec [Endogenous Compound] endothelial nitric oxide synthase/ec [Endogenous Compound] fibronectin/ec [Endogenous Compound] glycosylated hemoglobin/ec [Endogenous Compound] hemoglobin A1c/ec [Endogenous Compound] isophane insulin/ec [Endogenous Compound] kidney injury molecule 1/ec [Endogenous Compound] monocyte chemotactic protein 1/ec [Endogenous Compound] RNA 18S/ec [Endogenous Compound] tumor necrosis factor/ec [Endogenous Compound] enzyme linked immunosorbent assay female glucose blood level hyperglycemia image analysis immunohistochemistry kidney function *kidney injury male moderate renal impairment mouse nonhuman plethysmography streptozotocin-induced hyperglycemia systolic blood pressure weight height ratio real time polymerase chain reaction albuminuria animal cell animal experiment animal model animal tissue Article blood pressure body weight controlled study |
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