Background:

Nateglinide, a D-phenylalanine derivative, is an orally active and short-acting insulinotropic agent and a DPP IV inhibitor. Nateglinide inhibits ATP-sensitive K+ channels in pancreatic β-cells. Nateglinide is used for the treatment of type 2 (non-insulin-dependent) diabetes mellitus[1][2].

Nateglinide inhibits typical recordings of dinitrophenol-induced KATP currents in a concentration-dependent manner. Nateglinide exhibits IC50 values of 7.4 μM and 2.4 μM for 5 mM glucose (G5) and 16 mM (G16) glucose, respectively[2].

Nateglinide (50mg/kg, orally in mice) stimulates human C-peptide secretion in the humanized mice and improved postprandial glucose concentrations[3].

参考文献:
[1]. Christopher J. Dunn, et al. Nateglinide. OFILE Drugs 2000 Sep: 60 (3): 6.
[2]. Shiling Hu, et al. Interaction of nateglinide with KATP channel in h-cells underlies its unique insulinotropic action. European Journal of Pharmacology. 442 (2002) 163-171.
[3]. Jian Luo, et al. Evaluating insulin secretagogues in a humanized mouse model with functional human islets. Metabolism. 2013 Jan;62(1):90-9.
[4]. Duffy NA, et al. Effects of antidiabetic drugs on dipeptidyl peptidase IV activity: nateglinide is an inhibitor of DPP IV and augments the antidiabetic activity of glucagon-like peptide-1. Eur J Pharmacol. 2007 Jul 30;568(1-3):278-86.