Fig. 5

Niacin and insulin signaling. (A) Insulin binds its receptor on adipocytes and this receptor activates the AKT serine/threonine kinase (also known as protein kinase B). AKT generates downstream signals, including PDE3B (phosphodiesterase 3B) and HIF-1α (hypoxia inducible transcription factor-1α). HIF-1α cell signals promote glycolysis, lactate production, and the release of lactate from cells through the transporter, MCT1 (SLC16A1/monocarboxylate transporter 1). Hypoxia activates HIF-1α and its dimer partner HIF-1β but inhibits insulin receptor activation. HCARs (hydroxy-carboxylic acid receptors) are G-protein-coupled receptors. HCARs bind distinct ligands and induce Gi (inhibitory) signals to AC (adenylate cyclase) that catalyzes the formation of cAMP (cyclic adenosine monophosphate) from ATP (adenosine triphosphate). The function of HCAR1 may depend, in part, on the presence of HCAR2. PDE3B, Gi, and β-napthoflavone activated aryl hydrocarbon (AHR) signals antagonize lipolysis. Niacin also induces serum adiponectin production through HCAR2. (B) Insulin is produced by pancreatic islet beta-cells and circulates through the liver and kidney, as well as other tissues. Niacin inhibits insulin production and increases glomerular filtration rates (GFR) in CKD