title: Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis.
abstract: Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by (1)H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.
authors.affiliation: Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Covilhã, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Rato
authors.affiliation: Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Covilhã, Portugal ; Department of Life Sciences, Faculty of Sciences and Technology and Center for Neurosciences and Cell Biology (CNC), University of Coimbra, Portugal.
authors.forename: M G
authors.initials: MG
authors.lastname: Alves
authors.affiliation: Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Covilhã, Portugal.
authors.forename: T R
authors.initials: TR
authors.lastname: Dias
authors.affiliation: Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Covilhã, Portugal.
authors.forename: J E
authors.initials: JE
authors.lastname: Cavaco
authors.affiliation: Health Sciences Research Centre (CICS), Faculty of Health Sciences, University of Beira Interior (UBI), Covilhã, Portugal ; Department of Microscopy, Laboratory of Cell Biology, Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto, Portugal ; Unit for Multidisciplinary Research in Biomedicine (UMIB), Abel Salazar Institute of Biomedical Sciences (ICBAS), University of Porto (UP), Portugal.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000235:genetics / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D006019:Glycolysis / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010732:Phosphofructokinase-1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D013739:Testosterone; D004958:Estradiol; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D010732:Phosphofructokinase-1; D005947:Glucose