Elucidating the mechanism
Tissue samples measuring ~2 x 2 cm were excised at 0 min (acute), 2, 5, 15 or 60 min after injection and immediately frozen in 2-methyl-butane.To evaluate whether niacinamide and 1-methyl-niacinamide were entirely confined within the excised tissue, 1 cm thick sections along the four edges of the 0 min (acute) sample were also excised.Niacinamide mediates the acceleration of initial insulin aspart absorption, and the mechanism of action appears to be multifaceted.Niacinamide increases the initial abundance of insulin aspart monomers and transport of insulin aspart after subcutaneous administration, and also mediates a transient, local vasodilatory effect.Animal experiments were carried out in accordance with the Danish Act on Experiments on Animals, the Appendix A of ETS 123 and EU Directive 2010/63.A procedure project license was issued by the national authority.
Domestic pigs (Landrace-Yorkshire-Duroc [LYD]) were accommodated and cared for by competent personnel and supervised by laboratory animal veterinarians.
Animals were housed with 12-h day–night cycles with lights on at am, in a holding room with target temperatures of 21±2 °C and target relative humidity from 30–70%.
Pigs were single housed in enriched pens with the possibility of social interaction.
The composition of the formulations are shown in Table .
Formulations with 1-methyl-niacinamide, an analogue of niacinamide, were also administered.