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Abstract #2079

Stimulatory Effect of Glucokinase Activation on Hepatic Glycogen Turnover as Measured by 13C-MRS

Didier Laurent1, Brittany Yerby1, Jiaping Gao1, Alokesh Duttaroy1

1Novartis Institutes for Biomedical Research, Cambridge, MA, USA

A primary defect in hepatic glucose uptake may lead to an excessive rise in plasma glucose following meal ingestion. In response to rising levels of plasma glucose, glucokinase (GK) activation causes a shift in glucose metabolism towards storage and utilization. Here, we used 13C-MRS to measure, in a rat model of insulin resistance, the effects of a GK activator on hepatic G6P and glycogen contents. We demonstrate that GK activation is followed by a drastic increase in both glycogen synthesis and breakdown, suggesting that hepatic glycogen metabolism can be used as an early biomarker of drug efficacy.