In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. Suppl_1 ( 2020-09)
Abstract:
Diabetic kidney disease (DKD) is a severe complication of diabetes, which causes an increased risk of cardiovascular diseases and end-stage renal failure. Recent clinical data have demonstrated distinct sexual dimorphisms in the pathogenesis of DKD in humans, which impacts both severity- and age-related risk factors. A type 2 diabetic nephropathy (T2DN) rat model characterized by spontaneous development of an advanced form of diabetic nephropathy (DN) was used here to study sexual dimorphisms in the development of type 2 diabetes with DN. Male and female T2DN rats at late stages of the disease were used to evaluate hyperglycemia, renal injury, and kidney function. During late stage DKD ( 〉 46 weeks), glucose tolerance tests (GTT) revealed higher glucose levels in males (378 ± 19 vs. 183 ± 48 mg/dL) compared to females. This was accompanied by pathological changes in kidney function including urinary nephrin shedding, albuminuria (11.8 ± 5.7 vs. 0.98 ± 0.64 Alb/Cre ratio), and glomerular damage. To test the role of the endocrine environment in the pathophysiology of type 2 diabetes with DKD, we performed gonadectomies on male and female T2DN rats at 9 to 10 weeks of age, and animals were monitored until the full development of DKD ( 〉 46 weeks). All T2DN rats (intact and gonadectomized) maintained their diabetic phenotype, which was verified by higher end point blood glucose levels following a GTT (intact vs gonadectomized, male and female, respectively; 404 ± 21 vs 466 ± 32 and 264 ± 20 vs 291 ± 25 mg/dL). Based on kidneys to body weight ratios, gonadectomized male T2DN rats had a significant reduction in kidney hypertrophy (intact vs gonadectomized; males and females, respectively: 9.9 ± 0.2 vs 7.4 ± 0.2 and 7.7 ± 0.2 vs 7.0 ± 0.2 ratio). Moreover, FITC-inulin based GFR measurements revealed gonadectomized males had improved GFRs, whereas the GFRs of gonadectomized females rats were worsened (7.5 ± 1.5 vs. 4.1 ± 0.7 for male and 4.1 ± 0.2 vs. 7.3 ± 1.3 for female μg/mL/min; gonadectomy vs intact, correspondingly). In conclusion, male T2DN rats develop more severe DKD compared to age-matched females, and this phenotype is partially attenuated by the absence of sex hormones in males and exacerbated by the absence of hormones in females.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.76.suppl_1.MP09
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2020
detail.hit.zdb_id:
2094210-2
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