| In Vitro | In vitro activity: LY2608204 activates glucokinase (GK) with EC50 of 42 nM at 10 mM glucose with a concentration dependent manner at lower glucose concentrations. LY2608204 also stimulates glucose metabolism in rat insulinoma INS1-E cells with EC50 of 579 NM. |
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| In Vivo | LY2608204 decreases plasma glucose in a dose-dependent manner at both fasted and postprandial glucose levels. A maximal lowering of glucose AUC versus the untreated control group is observed with the high dose (30 mg/kg) and represents a 42% decrease. Interpolation of the data show that a 20% glucose AUC decrease occurs at an average LY2608204 concentration of 99 ng/mL (179 nM) in plasma, corresponding to a 6.9 mg/kg LY2608204 dose. The in vivo blood brain barrier permeability of LY2608204 results in a mean brain/plasma ratio of 0.17 five minutes post-dose with a mean total brain level of 0.539 nmol/g. |
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| Animal model | Male Wistar rats at a weight of 225-250 g |
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| Formulation & Dosage | Suspended in a 1:1 mixture of solutol/ethanol in a bath sonicator (10% of total volume). The obtained suspension is then diluted with 9 volumes of 10% aqueous solutol solution; 1, 3, 6, 10, 20 and 30 mg/kg; Orally, rats are given a 2 g/kg oral glucose bolus 2 hours after LY2608204 administration. |
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| References | J Biomol Struct Dyn. 2019 Jan 11:1-15. doi: 10.1080/07391102.2019.1567391. |
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