Thymosin β4 Attenuates Early Diabetic Nephropathy in a Mouse Model of Type 2 Diabetes Mellitus

2015 ◽  
Vol 22 (2) ◽  
pp. 141-146 ◽  
Author(s):  
Jian Zhu ◽  
Li-Ping Su ◽  
Yue Zhou ◽  
Lei Ye ◽  
Kok-Onn Lee ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Thymosin Β4 ◽  
Early Diabetic Nephropathy

scholarly journals Diabetic nephropathy in a nonobese mouse model of Type 2 diabetes mellitus

2014 ◽  
Vol 306 (9) ◽  
pp. F1008-F1017 ◽  
Author(s):  
Sandeep K. Mallipattu ◽  
Emily J. Gallagher ◽  
Derek LeRoith ◽  
Ruijie Liu ◽  
Anita Mehrotra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Large Body ◽  
Background Strain ◽  
Functional Inactivation ◽  
Novel Model

A large body of research has contributed to our understanding of the pathophysiology of diabetic nephropathy. Yet, many questions remain regarding the progression of a disease that accounts for nearly half the patients entering dialysis yearly. Several murine models of diabetic nephropathy secondary to Type 2 diabetes mellitus (T2DM) do exist, and some are more representative than others, but all have limitations. In this study, we aimed to identify a new mouse model of diabetic nephropathy secondary to T2DM in a previously described T2DM model, the MKR (MCK-KR-hIGF-IR) mouse. In this mouse model, T2DM develops as a result of functional inactivation of insulin-like growth factor-1 receptor (IGF-1R) in the skeletal muscle. These mice are lean, with marked insulin resistance, hyperinsulinemia, hyperglycemia, and dyslipidemia and thus are representative of nonobese human T2DM. We show that the MKR mice, when under stress (high-fat diet or unilateral nephrectomy), develop progressive diabetic nephropathy with marked albuminuria and meet the histopathological criteria as defined by the Animal Models of Diabetic Complications Consortium. Finally, these MKR mice are fertile and are on a common background strain, making it a novel model to study the progression of diabetic nephropathy.

Modulation of single-nephron GFR in the db/db mouse model of type 2 diabetes mellitus. II. Effects of renal mass reduction

2008 ◽  
Vol 294 (6) ◽  
pp. R1840-R1846 ◽  
Author(s):  
David Z. Levine ◽  
Michelle Iacovitti ◽  
Susan J. Robertson
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Mouse Model ◽  
Neuronal Nitric Oxide Synthase ◽  
Single Nephron ◽  
Oxide Synthase

This study examines for the first time the effects of uninephrectomy (Nx) on modulation of whole kidney glomerular filtration rate (GFR), single-nephron GFR (SNGFR), and progression of diabetic nephropathy in the db/db mouse model of type 2 diabetes mellitus. To characterize SNGFR and tubuloglomerular feedback (TGF) responses to Nx and chronic neuronal nitric oxide synthase inhibition in the db/db mouse, we studied the effects of Nx on whole kidney GFR, SNGFR, and TGF characteristics in db/db and wild-type (WT) mice after Nx or sham Nx. We also documented progression of glomerular changes over a 6-mo period. Whole kidney GFR and SNGFR were significantly higher in db/db Nx than db/db sham mice, without change in proximal tubule reabsorptive rates. The TGF responses, determined as proximal-distal SNGFR differences, were brisk: 12.1 ± 1.0 vs. 8.4 ± 0.6 nl/min in WT sham ( P < 0.05), 15.7 ± 1.0 vs. 12.0 ± 1.0 nl/min in WT Nx ( P < 0.05), and 17.8 ± 1.3 vs. 14.3 ± 1.0 nl/min in db/db Nx ( P < 0.05) mice. Chronic ingestion of the neuronal nitric oxide synthase inhibitor S-methylthiocitrulline for 2–3 wk after Nx had no effect on SNGFR or the TGF response. These studies show further elevations in whole kidney GFR and SNGFR in these hyperglycemic morbidly obese db/db mice, with an intact TGF system after Nx. In addition, in the db/db Nx mice, 4–6 mo after Nx, there was an exacerbation of the lesions of diabetic nephropathy, as quantified by a significant increase in the ratio of mesangial surface area to total glomerular surface area.

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