Figure 7.

Effects of diabetes on nicotinamide adenine dinucleotide (NAD⁺) metabolisms. In type 2 diabetes, reduced sirtuin‐1 (SIRT1)–liver kinase B1 (LKB1)–adenosine monophosphate‐activated protein kinase (AMPK) cascade (1–3) decreases nicotinamide phosphoribosyltransferase (NAMPT) expression (4), which decreases NAD⁺ synthesis. Increased reactive oxygen species (ROS) activates poly‐adenosine diphosphate ribosyl‐polymerase (PARP) (5) and increases NAD⁺ consumption. This reaction occurs strongly in insulinopenic type 1 diabetes. In both diabetes, decreased plasma thiamine and reduced transketolase activity might cause impaired phosphoribosyl diphosphate (PRPP) production (6). Excessive nicotinamide increases nicotinamide catabolites N1‐nicotinamide, N‐methyl‐2‐pyridone‐5‐carboxamide (2‐PY), 4‐PY production (7) and produces more H₂O₂ by aldehyde oxidase.