Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 75, Issue -, Pages 23-33Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2016.03.015
Keywords
Insulin; Podocyte; Autophagy; Reactive oxygen species; Filtration barrier permeability
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Funding
- National Science Center [2012/05/N/NZ5/00808, DEC-2014/12/T/NZ5/00273]
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Autophagy is an intracellular defense mechanism responsible for the turnover of damaged or nonfunctional cellular constituents. This process provides cells with energy and essential compounds under unfavorable environmental conditions-such as oxidative stress and hyperglycemia, which are both observed in diabetes. The most common diabetes complication is diabetic nephropathy (DN), which can lead to renal failure. This condition often includes impaired podocyte function. Here we investigated autophagic activity in rat podocytes cultured with a high insulin concentration (300 nM). Autophagy was activated after 60 min of insulin stimulation. Moreover, this effect was abolished following pharmacological (apocynin) or genetic (siRNA) inhibition of NAD(P)H oxidase activity, indicating that insulin-dependent autophagy stimulation involved reactive oxygen species (ROS). We also observed a continuous and time-dependent increase of podocyte albumin permeability in response to insulin, and this process was slightly improved by autophagy inhibition following short-term insulin exposure. Our results suggest that insulin may be a factor affecting the development of diabetic nephropathy. (C) 2016 Elsevier Ltd. All rights reserved.
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