Anomeric Specificity of the Stimulatory Effect of
D-Glucose on D-Fructose Phosphorylation by
Human Liver Glucokinase*
Hassan
Jijakli,
Philippe
Courtois,
Hai-Xia
Zhang,
Abdullah
Sener, and
Willy J.
Malaisse
From the Laboratory of Experimental Medicine, Brussels Free
University, B-1070 Brussels, Belgium
D-Glucose was recently reported
to stimulate D-fructose phosphorylation by human B-cell
glucokinase. The present study aims at investigating the anomeric
specificity of such a positive cooperativity. The
-anomer of
D-glucose was found to increase much more markedly than
-D-glucose the phosphorylation of D-fructose
by human liver glucokinase. Such an anomeric preference diminished at
high concentrations of the D-glucose anomers,
i.e. when the effect of the aldohexose upon
D-fructose phosphorylation became progressively less
marked. A comparison between the effects of the two anomers of
D-glucose and those of equilibrated D-glucose
upon D-fructose phosphorylation by human liver glucokinase
indicated that the results obtained with the equilibrated aldohexose
were not significantly different from those expected from the combined
effects of each anomers of D-glucose. In isolated rat
islets incubated for 60 min at 4 °C,
-D-glucose (5.6 mM), but not
-D-glucose (also 5.6 mM), augmented significantly the conversion of
D-[U-14C]fructose (5.0 mM) to
acidic radioactive metabolites. Likewise, in islets prelabeled with
45Ca and perifused at 37 °C, D-fructose
(20.0 mM) augmented 45Ca efflux and provoked a
biphasic stimulation of insulin release from islets exposed to
-D-glucose (5.6 mM), while inhibiting 45Ca efflux and causing only a sluggish and modest increase
in insulin output from islets exposed to
-D-glucose
(also 5.6 mM). The enhancing action of
D-glucose upon D-fructose phosphorylation by
glucokinase thus displays an obvious anomeric preference for
-D-glucose, and such an anomeric specificity remains
operative in intact pancreatic islets.
*
This work was supported by Grants 3.4567.97 and 3.4517.02 from the Belgian Foundation for Scientific Medical Research.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.