Regulation of liver glucokinase activity in rats with fructose-induced insulin resistance and impaired glucose and lipid metabolism

FRANCINI F; CASTRO MC; GAGLIARDINO JJ; MASSA ML

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY

NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS

Año: 2009 vol. 87 p. 702 - 710

0008-4212

Abstract: We evaluated the relative role of different liver glucokinase (GK) activity regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2), in intact animals with fructose-induced (FRD) insulin resistance and impaired glucose/lipid metabolism during 3 weeks. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content and GK activity, GK and PFK2 protein and gene expression in FRD and control rats. FRD rats had significantly higher blood glucose, insulin and triglyceride levels and liver triglyceride content, insulin resistance and impaired glucose tolerance. FRD rats have significantly higher GK activity in the cytosolic fraction (18.3 ± 0.35 and 11.27 ± 0.34 mU/mg protein; p <0.05). Differences in GK protein concentration were not significant (116 and 100%), suggesting a potentially impaired GK traslocation in FRD rats. While GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals; PFK2 immunological blockage decreased significantly GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals; under these conditions, PFK2 increase would be the main enhancer of GK activity.