Decreased expression of hepatic glucokinase in type 2 diabetes.
Mol Metab
; 4(3): 222-6, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-25737948
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Prognostic_studies
Language:
En
Journal:
Mol Metab
Year:
2015
Document type:
Article
Affiliation country:
United States