Annals of the New York Academy of Sciences · 1993 · 49 citations · 16 references
MedicineBiochemistryPharmacologyBiochemical PharmacologyCellular PharmacologyMolecular PharmacologyDiabetes MellitusDiabetes PharmacotherapyDiabetes PreventionEnzyme InhibitionNeuroprotectionNicotinamide Adenine Dinucleotide MetabolismFree Radical GenerationFree Radical ScavengingIslet Cell DysfunctionIslet Cell PhysiologyNad+ HomeostasisNicotinamide Adenine Dinucleotide (Nad+) MetabolismParp InhibitionProtective Treatments
Nicotinamide can protect the NOD mouse from diabetes if given early enough and in sufficient dose. The effect partly wanes with time. There is reduced islet inflammation. Similar protective effects can be demonstrated in quasi-experimental interventions in humans--both diabetes related and unrelated deemed at risk of developing diabetes by reason of having islet cell antibodies. Nicotinamide protects isolated islets in vitro from the toxicity of a number of agents, but only in doses that produce significant PARP inhibition, and increased intracellular levels of NAD. It is unlikely that the protective effect demonstrated in humans is due to significant PARP inhibition, as the levels of nicotinamide achieved with the doses used are too low. Other effects of the vitamin are more likely, e.g., increase in NAD pool size by de novo synthesis, or inhibition of free radical generation. The drug appears to be safe in the doses employed in humans.
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EVIDENCE FOR A LONG PREDIABETIC PERIOD IN TYPE I (INSULIN-DEPENDENT) DIABETES MELLITUS
A N Gorsuch, John Lister, B.M. Dean et al. · The Lancet · 1981 · 483 citations
Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes
Ezio Bonifacio, Marion Shattock, B.M. Dean et al. · The Lancet · 1990 · 351 citations
Affinity-purified human Interleukin I is cytotoxic to isolated islets of Langerhans
Thomas Mandrup‐Poulsen, Klaus Bendtzen, Jørn Nerup et al. · Diabetologia · 1986 · 324 citations · Full text