title: Albumin inhibits the insulin-mediated ACE2 increase in cultured podocytes.
abstract: Podocytes are key cells in the glomerular filtration barrier with a major role in the development of diabetic nephropathy. Podocytes are insulin-sensitive cells and have a functionally active local renin-angiotensin system. The presence and activity of angiotensin-converting enzyme 2 (ACE2), the main role of which is cleaving profibrotic and proinflammatory angiotensin-II into angiotensin-(1-7), have been demonstrated in podocytes. Conditionally immortalized mouse podocytes were cultured with insulin in the presence and absence of albumin. We found that insulin increases ACE2 gene and protein expression, by real-time PCR and Western blotting, respectively, and enzymatic activity within the podocyte and these increases were maintained over time. Furthermore, insulin favored an "anti-angiotensin II" regarding ACE/ACE2 gene expression balance and decreased fibronectin gene expression as a marker of fibrosis in the podocytes, all studied by real-time PCR. Similarly, insulin incubation seemed to protect podocytes from cell death, studied by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay. However, all these effects disappeared in the presence of albumin, which may mimic albuminuria, a main feature of DN pathophysiology. Our results suggest that modulation of renin-angiotensin system balance, fibrosis, and apoptosis by insulin in the podocyte may be an important factor in preventing the development and progression of diabetic kidney disease, but the presence of albuminuria seems to block these beneficial effects.
authors.affiliation: Department of Nephrology, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; and.
authors.forename: Eva
authors.initials: E
authors.lastname: Márquez
authors.affiliation: Department of Nephrology, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; and Red de Investigación Renal (REDINREN), Instituto Carlos III, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Riera
authors.affiliation: Department of Nephrology, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; and Red de Investigación Renal (REDINREN), Instituto Carlos III, Madrid, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Pascual
authors.affiliation: Department of Nephrology, Hospital del Mar, Barcelona, Spain; IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; and Red de Investigación Renal (REDINREN), Instituto Carlos III, Madrid, Spain msoler@parcdesalutmar.cat.
authors.forename: María José
authors.initials: MJ
authors.lastname: Soler
mesh_terms: D000418:Albumins / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology
chemical_list: D000418:Albumins; D007328:Insulin; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2
keywords: ACE2; albumin; insulin; podocytes; renin-angiotensin system