GKA50 quarterhydrate is a potent glucokinase activator (EC50=33 nM at 5 mM glucose). GKA50 quarterhydrate stimulates insulin release from mouse islets of Langerhans and MIN6 cells. GKA50 quarterhydrate shows significant glucose lowering in high fat fed female rats[1][2].
GKA50 (0.01-100 μM; 24 hours) enhances INS-1 cell proliferation with EC50 values 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: INS-1 cells (starved overnight with 3 μM glucose)
GKA50 (1-30 mg/kg; p.o.) gives significant glucose lowering in an oral glucose tolerance test[1]. Animal Model: High-fat-fed obese female Zucker (fa/fa) rats[1]
[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.