title: Metabolic fingerprints in testicular biopsies from type 1 diabetic patients.
abstract: Diabetes mellitus (DM) is a metabolic disease that has grown to pandemic proportions. Recent reports have highlighted the effect of DM on male reproductive function. Here, we hypothesize that testicular metabolism is altered in type 1 diabetic (T1D) men seeking fertility treatment. We propose to determine some metabolic fingerprints in testicular biopsies of diabetic patients. For that, testicular tissue from five normal and five type 1 diabetic men was analyzed by high-resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy. mRNA and protein expression of glucose transporters and glycolysis-related enzymes were also evaluated. Our results show that testes from diabetic men presented decreased levels of lactate, alanine, citrate and creatine. The mRNA levels of glucose transporter 1 (GLUT1) and phosphofructokinase 1 (PFK1) were decreased in testes from diabetic men but only GLUT3 presented decreased mRNA and protein levels. Lactate dehydrogenase (LDH) and glutamate pyruvate transaminase (GPT) protein levels were also found to be decreased in testes from diabetic men. Overall, our results show that T1D alters glycolysis-related transporters and enzymes, compromising lactate content in the testes. Moreover, testicular creatine content was severely depressed in T1D men. Since lactate and creatine are essential for germ cells development and support, the data discussed here open new insights into the molecular mechanism by which DM promotes subfertility/infertility in human males.
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506, Covilhã, Portugal. alvesmarc@gmail.com.
authors.forename: Marco G
authors.initials: MG
authors.lastname: Alves
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506, Covilhã, Portugal.|Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Multidisciplinary Unit for Biomedical Research (UMIB), University of Porto, 4050-313, Porto, Portugal.
authors.forename: Ana D
authors.initials: AD
authors.lastname: Martins
authors.affiliation: Laboratory of Physiology, Faculty of Medicine, University of Coimbra, 3000-548, Coimbra, Portugal.|CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517, Coimbra, Portugal.|Department of Life Sciences, Faculty of Science and Technology (FCTUC), University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Rui A
authors.initials: RA
authors.lastname: Carvalho
authors.affiliation: Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Multidisciplinary Unit for Biomedical Research (UMIB), University of Porto, 4050-313, Porto, Portugal.|Centre for Reproductive Genetics Prof. Alberto Barros, 4100-009, Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.affiliation: Centre for Reproductive Genetics Prof. Alberto Barros, 4100-009, Porto, Portugal.|Department of Genetics, Faculty of Medicine, University of Porto, 4200 - 319, Porto, Portugal.
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
authors.affiliation: Centre for Reproductive Genetics Prof. Alberto Barros, 4100-009, Porto, Portugal.
authors.forename: Joaquina
authors.initials: J
authors.lastname: Silva
authors.affiliation: Center of Reproductive Medicine, Maternity Dr. Alfredo da Costa, Centro Hospitalar de Lisboa Central (CHLC), 1069-089, Lisboa, Portugal.
authors.forename: Soraia
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Center of Reproductive Medicine, Maternity Dr. Alfredo da Costa, Centro Hospitalar de Lisboa Central (CHLC), 1069-089, Lisboa, Portugal.
authors.forename: Teresinha
authors.initials: T
authors.lastname: Simões
authors.affiliation: CICS - UBI - Health Sciences Research Centre, University of Beira Interior, 6201-506, Covilhã, Portugal. pfobox@gmail.com.|Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS) and Multidisciplinary Unit for Biomedical Research (UMIB), University of Porto, 4050-313, Porto, Portugal. pfobox@gmail.com.
authors.forename: Pedro Fontes
authors.initials: PF
authors.lastname: Oliveira
mesh_terms: D001706:Biopsy; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D012098:Reproduction / Q000502:physiology; D013737:Testis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C495687:SLC2A3 protein, human; D007770:L-Lactate Dehydrogenase
keywords: Diabetes; Lactate; Metabolism; Spermatogenesis; Testes