title: Involvement of the AMPK-PTEN pathway in insulin resistance induced by high glucose in cultured rat podocytes.
abstract: As part of the filtration barrier, podocytes play an important role in the development of diabetic nephropathy. Disturbances in insulin signaling accompanied by insulin resistance can lead to various intracellular events. We hypothesized that high glucose concentrations would lead to disturbances in interactions between AMPK and PTEN proteins in podocytes. Experiments were performed in primary rat podocytes cultured with normal (5.6mM) or high (30mM) glucose concentrations for 5d. Immunodetection methods were used to detect AMPK, PTEN, insulin receptor, and Akt proteins, and their phosphorylated forms. Insulin-stimulated changes in glucose uptake were used to detect insulin resistance. Isoforms of AMPK were detected by RT-PCR. AMPK and PTEN activities were modified by metformin, Compound C, siRNA for AMPK isoforms α1 and α2 and siRNA for PTEN, respectively. We found that impairment of insulin induction of glucose uptake into podocytes cultivated in the presence of high glucose concentrations for long periods of time is associated with increased PTEN levels in an AMPK-dependent manner.
authors.affiliation: Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Science, Gdańsk, Poland. Electronic address: drogacka@imdik.pan.pl.
authors.forename: Dorota
authors.initials: D
authors.lastname: Rogacka
authors.affiliation: Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Science, Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Piwkowska
authors.affiliation: Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Science, Gdańsk, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Audzeyenka
authors.affiliation: Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Science, Gdańsk, Poland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Angielski
authors.affiliation: Laboratory of Molecular and Cellular Nephrology, Mossakowski Medical Research Centre, Polish Academy of Science, Gdańsk, Poland; Department of Therapy Monitoring and Pharmacogenetics, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Jankowski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008687:Metformin / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014162:Transfection
chemical_list: D008687:Metformin; D055372:AMP-Activated Protein Kinases; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; D005947:Glucose
keywords: AMPK; Hyperglycemia; Metformin; PTEN; Podocytes