Nicotinamide Mononucleotide in the Context of Elevated Plasma Levels of Free Fatty Acids Improves Glucose Tolerance by Decreasing Insulin Clearance

The NAD-dependent deacetylase SIRT1 has been shown to be beneficial to beta cell function. Nicotinamide Mononucleotide (NMN), the product of the rate-limiting enzyme in NAD synthesis, has recently been shown to have positive effects on glucose tolerance in mice fed a high fat diet. This is the first study to examine the effects of NMN on insulin clearance and FFA-induced beta cell dysfunction. NMN was i.v. infused, with or without oleate, in C57BL/6 mice over 48h in order to elevate intracellular NAD levels and consequently increase SIRT1 activity. We demonstrated that administration of NMN in the context of elevated plasma FFA levels results in a significant decrease in insulin clearance as well as partial protection against FFA-induced beta cell dysfunction in vivo. This culminated in a large improvement in glucose tolerance. In summary, NMN may have a therapeutic potential to improve glucose tolerance in conditions of increased plasma FFA levels, which is typical in patients with type 2 diabetes mellitus.M.Sc.2018-07-05 00:00:0