Compromised chronic efficacy of a Glucokinase Activator AZD1656 in mouse models for common humanGCKRvariants
Brian E Ford,
Shruti S Chachra,
Ahmed Alshawi
et al.
Abstract:Glucokinase activators (GKAs) have been developed as blood glucose lowering drugs for type 2 diabetes. Despite good short-term efficacy, several GKAs showed a decline in efficacy chronically during clinical trials. The underlying mechanisms remain incompletely understood. We tested the hypothesis that deficiency in the liver glucokinase regulatory protein (GKRP) as occurs with common human GCKR variants affects chronic GKA efficacy. We used a Gckr-P446L mouse model for the GCKR exonic rs1260326 (P446L) variant… Show more
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