title: Pyridoxal 5'-phosphate (PLP) deficiency might contribute to the onset of type I diabetes.
abstract: The incidence of type I diabetes is rising worldwide, particularly in young children. Type I diabetes is considered a multifactorial disease with genetic predisposition and environmental factors participating. Currently, despite years of research, there is no consensus regarding the factors that initiate the autoimmune response. Type I diabetes is preceded by autoimmunity to islet antigens, among them the protein glutamic acid decarboxylase, GAD-65. Pyridoxal 5'-phosphate (PLP) is formed from vitamin B6 by the action of pyridoxal kinase. Interaction of GAD65 with PLP is necessary for GAD65-mediated synthesis of the neurotransmitter γ-aminobutyric acid (GABA). PLP is also a required cofactor for dopamine synthesis by L-aromatic decarboxylase (L-AADC). Both GAD65 and L-AADC are expressed in pancreatic islets. Here it is proposed that lack of the vitamin B6 derivative pyridoxal 5'-phosphate might contribute to the appearance of pancreatic islet autoimmunity and type I diabetes onset.
authors.affiliation: Department of Experimental and Health Sciences (DCEXS), Pompeu Fabra University, PRBB-Barcelona Biomedical Research Park, c/ Dr. Aiguader, 88 E-08003 Barcelona, Spain. blanca.rubi@upf.edu
authors.forename: B
authors.initials: B
authors.lastname: Rubí
mesh_terms: D015551:Autoimmunity / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology* / Q000378:metabolism; D008954:Models, Biological; D011732:Pyridoxal Phosphate / Q000172:deficiency* / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
chemical_list: D005680:gamma-Aminobutyric Acid; D011732:Pyridoxal Phosphate; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2