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Published on: June 25, 2017
Decreased expression of hepatic glucokinase in type 2 diabetes
Rebecca A Haeusler1, Stefania Camastra2, Brenno Astiarraga2
1Columbia University, Department of Pathology and Cell Biology, New York, NY, USA.
Background/Objectives:
Increased endogenous glucose production is a hallmark of type 2 diabetes. Evidence from animal models has suggested that a likely cause of this is increased mRNA expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase (encoded by G6PC, PCK1 and PCK2). But another contributing factor may be decreased liver glucokinase (encoded by GCK).
Methods:
We examined expression of these enzymes in liver biopsies from 12 nondiabetic and 28 diabetic individuals. Diabetic patients were further separated into those with HbA1c lower or higher than 7.0.
Results:
In diabetic subjects with HbA1c > 7.0, we found that gluconeogenic enzymes were expressed normally, but GCK was suppressed more than 60%. Moreover, HbA1c and fasting glucose were negatively correlated with GCK, but showed no correlation with G6PC, PCK1, or PCK2.
Conclusion:
These findings suggest an underlying dysregulation of hepatic GCK expression during frank diabetes, which has implications for the therapeutic use of glucokinase activators in this population.
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