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Am J Physiol Renal Physiol. 2013 Jul 15;305(2):F182-8. doi: 10.1152/ajprenal.00548.2012. Epub 2013 May 22.

Insulin directly stimulates VEGF-A production in the glomerular podocyte.

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1
Academic and Children's Renal Unit, University of Bristol, Learning and Research building, Southmead Hospital, Bristol, United Kingdom.

Abstract

Podocytes are critically important for maintaining the integrity of the glomerular filtration barrier and preventing albuminuria. Recently, it has become clear that to achieve this, they need to be insulin sensitive and produce an optimal amount of VEGF-A. In other tissues, insulin has been shown to regulate VEGF-A release, but this has not been previously examined in the podocyte. Using in vitro and in vivo approaches, in the present study, we now show that insulin regulates VEGF-A in the podocyte in both mice and humans via the insulin receptor (IR). Insulin directly increased VEGF-A mRNA levels and protein production in conditionally immortalized wild-type human and murine podocytes. Furthermore, when podocytes were rendered insulin resistant in vitro (using stable short hairpin RNA knockdown of the IR) or in vivo (using transgenic podocyte-specific IR knockout mice), podocyte VEGF-A production was impaired. Importantly, in vivo, this occurs before the development of any podocyte damage due to podocyte insulin resistance. Modulation of VEGF-A by insulin in the podocyte may be another important factor in the development of glomerular disease associated with conditions in which insulin signaling to the podocyte is deranged.

KEYWORDS:

insulin; podocyte; podocyte-specific insulin receptor knockout mice; vascular endothelial growth factor-A

PMID:
23698113
PMCID:
PMC3725664
DOI:
10.1152/ajprenal.00548.2012
[Indexed for MEDLINE]
Free PMC Article
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