| Bioactivity | GKA50 is a potent glucokinase activator (EC50=33 nM at 5 mM glucose). GKA50 stimulates insulin release from mouse islets of Langerhans. GKA50 is a glucose-like activator of beta-cell metabolism in rodent and human islets and a Ca2+-dependent modulator of insulin secretion. GKA50 shows significant glucose lowering in high fat fed female rats[1][2][3][4]. | |||||||||
| Invitro | GKA50 (0.01-100 μM; 24 hours) enhances INS-1 cell proliferation with EC50values ranging from 1 to 2 μM[2].GKA50 (1.2 μM+40 μM glucose; 2-4 days) treatment reduces apoptosis induced by chronic high glucose in INS-1 cells[2].GKA50 activates human glucokinase enzymatic activity with an EC50 of 0.022 μM. GKA50 stimulates insulin secretion in the pancreatic insulinoma cell line, INS-1, with an EC50 of 0.065 μM. GKA50 reduces chronic-high-glucose-induced apoptosis via modulation of glucokinase and apoptotic protein BAD[2]. Cell Proliferation Assay[2] Cell Line: | |||||||||
| In Vivo | GKA50 (1-30 mg/kg; p.o.) gives significant glucose lowering in an oral glucose tolerance test[1]. Animal Model: | |||||||||
| Name | GKA50 | |||||||||
| CAS | 851884-87-2 | |||||||||
| Formula | C26H28N2O6 | |||||||||
| Molar Mass | 464.51 | |||||||||
| Appearance | Solid | |||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | |||||||||
| Storage |
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| Reference | [1]. Coope GJ, et al. Predictive blood glucose lowering efficacy by Glucokinase activators in high fat fed female Zucker rats. Br J Pharmacol. 2006 Oct;149(3):328-35. [2]. McGlasson L, et al. The glucokinase activator GKA50 causes an increase in cell volume and activation of volume-regulated anion channels in rat pancreatic β-cells. Mol Cell Endocrinol. 2011 Aug 6;342(1-2):48-53. [3]. Johnson D, et al. Glucose-dependent modulation of insulin secretion and intracellular calcium ions by GKA50, a glucokinase activator. Diabetes. 2007;56(6):1694-1702. |