Faculty Collaboration Database

Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN rats. Physiol Genomics 2021 Jun 01;53(6):223-234

Date

04/20/2021

Pubmed ID

33870721

Pubmed Central ID

PMC8285576

DOI

10.1152/physiolgenomics.00009.2021

Scopus ID

2-s2.0-85108022875 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Diabetic kidney disease (DKD) is a common complication of diabetes, which frequently leads to end-stage renal failure and increases cardiovascular disease risk. Hyperglycemia promotes renal pathologies such as glomerulosclerosis, tubular hypertrophy, microalbuminuria, and a decline in glomerular filtration rate. Importantly, recent clinical data have demonstrated distinct sexual dimorphism in the pathogenesis of DKD in people with diabetes, which impacts both severity- and age-related risk factors. This study aimed to define sexual dimorphism and renal function in a nonobese type 2 diabetes model with the spontaneous development of advanced diabetic nephropathy (T2DN rats). T2DN rats at 12- and over 48-wk old were used to define disease progression and kidney injury development. We found impaired glucose tolerance and glomerular hyperfiltration in T2DN rats to compare with nondiabetic Wistar control. The T2DN rat displays a significant sexual dimorphism in insulin resistance, plasma cholesterol, renal and glomerular injury, urinary nephrin shedding, and albumin handling. Our results indicate that both male and female T2DN rats developed nonobese type 2 DKD phenotype, where the females had significant protection from the development of severe forms of DKD. Our findings provide further evidence for the T2DN rat strain's effectiveness for studying the multiple facets of DKD.

Author List

Spires DR, Palygin O, Levchenko V, Isaeva E, Klemens CA, Khedr S, Nikolaienko O, Kriegel A, Cheng X, Yeo JY, Joe B, Staruschenko A

Authors

Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Alison J. Kriegel PhD Associate Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Albuminuria
Animals
Biomarkers
Blood Glucose
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Disease Progression
Electrolytes
Female
Glomerular Filtration Rate
Glucose Tolerance Test
Humans
Insulin Resistance
Kidney
Male
Metabolomics
Rats, Wistar
Sex Factors