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Pathway Description
Repaglinide Action Pathway
Homo sapiens
Drug Action Pathway
Repaglinide is a non-sulfonylurea insulin secretagogue used in the treatment of type 2 diabetes. As the name of the drug class suggests, repaglinide acts on pancreatic beta-cells to stimulate insulin secretion. Under physiological conditions, insulin secretion from beta-cells is mediated by elevated glucose concentration in the blood. Glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentration of ATP will inhibit ATP-dependent potassium channels (ABCC8), which depolarizes the cell. Depolarization causes opening of voltage-gated calcium channels, allowing calcium to enter cell. High intracellular calcium subsequently stimulate vesicle exocytosis and insulin secretion. Repaglinide stimulate insulin secretion in a glucose-sensitive manner by inhibiting ATP-dependent potassium channels. As a result, there tends to be a lesser likelihood of hypoglycemia with repaglinide therapy compared to sulfonylureas.
References
Repaglinide Pathway References
Dornhorst A: Insulinotropic meglitinide analogues. Lancet. 2001 Nov 17;358(9294):1709-16. doi: 10.1016/S0140-6736(01)06715-0.
Pubmed: 11728565
Mizuno CS, Chittiboyina AG, Kurtz TW, Pershadsingh HA, Avery MA: Type 2 diabetes and oral antihyperglycemic drugs. Curr Med Chem. 2008;15(1):61-74.
Pubmed: 18220763
Pancreas Function References
Roder PV, Wu B, Liu Y, Han W: Pancreatic regulation of glucose homeostasis. Exp Mol Med. 2016 Mar 11;48:e219. doi: 10.1038/emm.2016.6.
Pubmed: 26964835
Gaisano HY, Macdonald PE, Vranic M: Glucagon secretion and signaling in the development of diabetes. Front Physiol. 2012 Sep 4;3:349. doi: 10.3389/fphys.2012.00349. eCollection 2012.
Pubmed: 22969729
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