title: 1,25-Dihydroxyvitamin D increases the gene expression of enzymes protecting from glucolipotoxicity in peripheral blood mononuclear cells and human primary endothelial cells.
abstract: Besides its classical function as an orchestrator of calcium and phosphorus homeostasis, vitamin D also affects insulin secretion and tissue efficiency. A number of studies have consistently reported the inverse relationship between vitamin D deficiency and type 2 diabetes. Activation of certain metabolic pathways and down-stream transcription factors may protect from glucolipotoxicity and their targeted activation -e.g. by vitamin D - might explain the detrimental role of vitamin D deficiency in diabetes. The aim of the study was to quantify gene and protein expression of selected enzymes involved in the protection from glucolipotoxicity, specifically glyoxalase 1 (GLO1), and other enzymes with antioxidant activity - hemoxygenase (HMOX), thiamin pyrophosphokinase (TPK1) and transketolase (TKT), under normo- and hyperglycemic conditions and upon addition of vitamin D in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The results of our study indicate that the active form of vitamin D regulates gene expression of enzymes opposing the harmful effect of glucolipotoxicity whose activities appear to be suppressed by hyperglycemia. However, we were unable to confirm this effect on protein expression. While we cannot speculate on the effect of vitamin D on diabetes itself our results support its role in the protection against existing glucolipotoxicity therefore possibly translating into the prevention of development of diabetic complications.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic. katarina.kuricova@gmail.com pleskacova@mail.muni.cz paci@med.muni.cz kankov@med.muni.cz.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kuricova
authors.forename: Anna
authors.initials: A
authors.lastname: Pleskacova
authors.forename: Lukas
authors.initials: L
authors.lastname: Pacal
authors.forename: Katerina
authors.initials: K
authors.lastname: Kankova
mesh_terms: D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000201:enzymology; D013836:Thiamin Pyrophosphokinase / Q000235:genetics / Q000378:metabolism*; D014174:Transketolase / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D007328:Insulin; D014807:Vitamin D; D014174:Transketolase; D013836:Thiamin Pyrophosphokinase; C000597196:GLO1 protein, human; D007791:Lactoylglutathione Lyase