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Characterization of a novel glucokinase activator in rat and mouse models.

ABSTRACT: Glucokinase (GK) is a hexokinase isozyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate. Glucokinase activators are being investigated as potential diabetes therapies because of their effects on hepatic glucose output and/or insulin secretion. Here, we have examined the efficacy and mechanisms of action of a novel glucokinase activator, GKA23. In vitro, GKA23 increased the affinity of rat and mouse glucokinase for glucose, and increased glucose uptake in primary rat hepatocytes. In vivo, GKA23 treatment improved glucose homeostasis in rats by enhancing beta cell insulin secretion and suppressing hepatic glucose production. Sub-chronic GKA23 treatment of mice fed a high-fat diet resulted in improved glucose homeostasis and lipid profile.

SUBMITTER: Lu M

PROVIDER: S-EPMC3922816 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Characterization of a novel glucokinase activator in rat and mouse models.

Lu Min M Li Pingping P Bandyopadhyay Gautam G Lagakos William W Dewolf Walter E WE Alford Taylor T Chicarelli Mark Joseph MJ Williams Lance L Anderson Deborah A DA Baer Brian R BR McVean Maralee M Conn Marion M Véniant Murielle M MM Coward Peter P

PloS one 20140212 2

Glucokinase (GK) is a hexokinase isozyme that catalyzes the phosphorylation of glucose to glucose-6-phosphate. Glucokinase activators are being investigated as potential diabetes therapies because of their effects on hepatic glucose output and/or insulin secretion. Here, we have examined the efficacy and mechanisms of action of a novel glucokinase activator, GKA23. In vitro, GKA23 increased the affinity of rat and mouse glucokinase for glucose, and increased glucose uptake in primary rat hepatoc ...[more]

PMID: 24533087

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Chronic glucokinase activator treatment at clinically translatable exposures gives durable glucose lowering in two animal models of type 2 diabetes.

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