title: Molecular mechanisms of beta-cell destruction in IDDM: the role of nicotinamide.
abstract: Autoimmune processes are involved in pancreatic beta-cell destruction in type 1 diabetes. Autoantibodies including islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA), and antibodies directed against the 37/ 40 K antigen appear in the circulation years before clinical onset and permit increasingly precise disease prediction. A cellular immune response causes pancreatic infiltration, while macrophages and Th-cells appear to be implicated-via local release of cytokines-in beta-cell destruction. Generation of free radicals, DNA strand breaks, activation of the enzyme poly (ADP-ribose) polymerase (PARP), and depletion of intracellular nicotinamide adenine dinucleotide (NAD) appear to be common factors in beta-cell death, whether mediated by oxygen radicals, nitric oxide, or streptozotocin. Nicotinamide, a soluble B group vitamin which offers protection against these toxic stimuli, is at high doses a free radical scavenger, a potent inhibitor of PARP, and protects against depletion of intracellular NAD. A sound scientific rationale therefore exists for its use in human prediabetes, and promising pilot studies have been performed in ICA-positive first-degree relatives and school children. No serious side effects have been reported from its use at the doses proposed in man or other species. There is therefore a sound case for submitting this agent to a controlled clinical trial.
authors.affiliation: Department of Diabetes and Metabolism, St Bartholomew's Hospital, London, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Gale
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D007515:Islets of Langerhans / Q000502:physiology*; D009536:Niacinamide / Q000502:physiology* / Q000627:therapeutic use*; D011236:Prediabetic State / Q000188:drug therapy
chemical_list: D009536:Niacinamide