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Nateglinide-d5 is intended for use as an internal standard for the quantification of nateglinide by GC- or LC-MS. Nateglinide is a hypoglycemic agent.1,2,3 It induces insulin and somatostatin release from perfused rat pancreas when used at concentrations ranging from 0.03 to 3 μM.1 Nateglinide (3 µM) increases intracellular calcium levels in isolated rat pancreatic β cells, an effect that can be inhibited by the L-type calcium channel blocker nitrendipine . Nateglinide-induced secretion of insulin and somatostatin and calcium influx is also reversed by the potassium channel activator diazoxide . Oral administration of nateglinide (1.6 mg/kg) reduces blood glucose levels by 20% in fasted mice.2 It also decreases blood glucose levels in an oral glucose tolerance test in normal rats, genetically diabetic KK mice, and a rat model of diabetes induced by streptozotocin .3 Formulations containing nateglinide have been used in the treatment of type 2 diabetes.

1.Fujitani, S., Ikenoue, T., Akiyoshi, M., et al.Somatostatin and insulin secretion due to common mechanisms by a new hypoglycemic agent, A-4166, in perfused rat pancreasMetabolism45(2)184-189(1996) 2.Shinkai, H., Toi, K., Kumashiro, I., et al.N-acylphenylalanines and related compounds. A new class of oral hypoglycemic agentsJ. Med. Chem.31(11)2092-2097(1988) 3.Sato, Y., Nishikawa, M., Shinkai, H., et al.Possibility of ideal blood glucose control by a new oral hypoglycemic agent, N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166), and its stimulatory effect on insulin secretion in animalsDiabetes Res. Clin. Pract.12(1)53-59(1991)

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