title: Pioglitazone increases the glycolytic efficiency of human Sertoli cells with possible implications for spermatogenesis.
abstract: Pioglitazone is a synthetic agonist for the nuclear receptor peroxisome proliferator-activated receptor γ used to treat type 2 diabetes mellitus. Recently we reported that antidiabetic drugs regulate the nutritional support of spermatogenesis by Sertoli cells. Herein, we investigate the effects of pioglitazone on human Sertoli cells metabolism. Human Sertoli cells were cultured in the presence of pioglitazone (1, 10, 100μM). Protein levels of phosphofructokinase 1, lactate dehydrogenase, hexokinase, glucose transporters (GLUT1, GLUT2, GLUT3), monocarboxylate transporter 4 and oxidative phosphorylation complexes were determined by Western blot. Lactate dehydrogenase and alanine aminotransferase activity were assessed and metabolite production and consumption determined by proton nuclear magnetic resonance. Mitochondrial membrane potential was also determined. Glucose consumption more than doubled in human Sertoli cells stimulated with pioglitazone 100μM. Mitochondrial complex II protein levels increased 50% with exposure to pioglitazone (100μM) in human Sertoli cells, though mitochondrial membrane potential was decreased by 32%. The pharmacological concentration of pioglitazone (10μM) almost doubled lactate production and established crucial correlations among key intervenient of glycolysis. Moreover, in the same concentration, alanine aminotransferase decreased more than 80%. Our results suggest that pioglitazone (10μM) increases the efficiency of the glycolytic flux and lactate production by human Sertoli cells, which is essential to sustain and preserve the spermatogenic event. Thus, pioglitazone may improve male fertility and thus, be considered a suitable antidiabetic drug for men in reproductive age.
authors: Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal; CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal.
authors: M J
authors: MJ
authors: Meneses
authors: Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal.
authors: R L
authors: RL
authors: Bernardino
authors: Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal.
authors: R
authors: R
authors: Sá
authors: Centre for Reproductive Genetics Professor Alberto Barros, 4100-009 Porto, Portugal.
authors: J
authors: J
authors: Silva
authors: Centre for Reproductive Genetics Professor Alberto Barros, 4100-009 Porto, Portugal; Department of Genetics, Faculty of Medicine, University of Porto, 4100-009 Porto, Portugal; i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4100-009 Porto, Portugal.
authors: A
authors: A
authors: Barros
authors: Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal; Centre for Reproductive Genetics Professor Alberto Barros, 4100-009 Porto, Portugal.
authors: M
authors: M
authors: Sousa
authors: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal.
authors: B M
authors: BM
authors: Silva
authors: Department of Microscopy, Laboratory of Cell Biology and Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, 4050-313 Porto, Portugal; i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, 4100-009 Porto, Portugal.
authors: P F
authors: PF
authors: Oliveira
authors: CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal. Electronic address: alvesmarc@gmail.com.
authors: M G
authors: MG
authors: Alves
mesh_terms: D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D019344:Lactic Acid / Q000096:biosynthesis; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D000077205:Pioglitazone; D019289:Pyruvic Acid / Q000378:metabolism; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism*; D013091:Spermatogenesis / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D045162:Thiazolidinediones; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D000077205:Pioglitazone
keywords: Mitochondria; Pioglitazone; Sertoli cells; Spermatogenesis