Premium
Utilizing a Type 1 Diabetic Nephropathy Model Developed on the Basis of Streptozotocin‐Treated Dahl SS Rats for the Studies of Calcium Handling in the Podocytes
Author(s) -
Lowing Andrea,
Ilatovskaya Daria,
Palygin Oleg,
Pavlov Tengis,
Levchenko Vladislav,
Staruschenko Alexander
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.964.2
Subject(s) - diabetic nephropathy , streptozotocin , podocyte , nephrin , endocrinology , medicine , glomerulosclerosis , excretion , proteinuria , kidney , calcium , diabetes mellitus , chemistry , nephropathy
Podocytes play a key role in the development of nephropathy: podocyte depletion results in reduced GFR and progressive glomerulosclerosis. Circulating factors can activate calcium influx in these cells triggering processes that lead to podocyte loss. This study was aimed at developing a proper model of diabetic nephropathy (DN) on the basis of the Dahl Salt‐Sensitive (SS) rat that could be further used for assessing calcium signaling in podocytes. Type I diabetes was induced in 6 week old SS rats by an injection of 75 mg/kg streptozotocin (STZ) which caused an elevation of blood glucose up to 700 mg/dL; this was then decreased to 350 mg/dL by an insulin pellet implant. Rats were monitored throughout the next 6 or 12 weeks; urine analyses revealed progressive proteinuria, whereas sodium and potassium fractional excretion levels were normal in both control and diabetic groups (0.3 and 14 for fractional excretion of Na and K, respectively). However, 6 weeks after the STZ injection was not sufficient to develop histological features characteristic in DN, whereas the 12 week treatment resulted in typical DN kidney damage. Urinary ELISA showed a 50‐fold increase in nephrin excretion in the 12 week hyperglycemic animals, which is indicative of podocyte depletion and foot processes effacement. At the end of the experiment rat glomeruli were isolated and successfully used for ratiometric confocal measurements with fluorescent dyes or patch‐clamp measurements. In conclusion, this rat model shows the features of diabetic kidney injury and is a good basis for the assessment of calcium signaling and glomerular filtration barrier function during type 1 DN.