Pyridoxal 5'-phosphate (PLP) deficiency might contribute to the onset of type I diabetes

Med Hypotheses. 2012 Jan;78(1):179-82. doi: 10.1016/j.mehy.2011.10.021. Epub 2011 Nov 15.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmunity / immunology*
  • Diabetes Mellitus, Type 1 / etiology*
  • Glutamate Decarboxylase / metabolism
  • Humans
  • Islets of Langerhans / immunology*
  • Islets of Langerhans / metabolism
  • Models, Biological*
  • Pyridoxal Phosphate / deficiency*
  • Pyridoxal Phosphate / metabolism
  • gamma-Aminobutyric Acid / biosynthesis


  • gamma-Aminobutyric Acid
  • Pyridoxal Phosphate
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2