| Authors |
Mallipattu SK, Gallagher EJ, Leroith D, Liu R, Mehrotra A, Horne SJ, Chuang PY,
Yang VW, He JC
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| Submitted By |
Submitted Externally on 3/12/2014 |
| Status |
Published |
| Journal |
American journal of physiology. Renal physiology |
| Year |
2014 |
| Date Published |
3/5/2014 |
| Volume : Pages |
306 : F1008 - F1017 |
| PubMed Reference |
24598803 |
| Abstract |
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, 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 non-obese 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.
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