Environmental modulation of D-fructose insulinotropic action.
At concentrations in excess of about 80 mmol/l, D-fructose stimulates insulin release from rat islets incubated in the absence of any other exogenous nutrient, an optimal secretory response being recorded in the 240 to 320 mmol/l range. D-galactose and 3-O-methyl-D-glucose fail to reproduce the insulinotropic action of D-fructose. At a concentration of D-fructose close to the threshold value for such an insulinotropic action (80 mmol/l), as little as 1.0-4.0 mmol/l D-glucose is sufficient to increase insulin release, with a sigmoidal concentration-response relationship similar to that otherwise evoked by much higher concentrations of the aldohexose. The release of insulin evoked by D-fructose (240 mmol/l) is abolished in the absence of Ca2+ or presence of KCN (2.0 mmol/l), partially inhibited by 3-O-methyl-D-glucose (80 mmol/l) or D-mannoheptulose (1.0 mmol/l), and potentiated by forskolin (10 micromol/l), theophylline (1.4 mmol/l), cytochalasin B (21 micromol/l) and glibenclamide (5 micromol/l). These findings indicate that the stimulation of insulin release by high concentrations of D-fructose corresponds to an active secretory process modulated by the metabolic fate of the hexose, the availability of ATP, the activity of ATP-sensitive K+ channels, the extracellular concentration of Ca2+, the cell content in cyclic AMP and the motile events under the control of the microfilamentous cell web.
Sener
A
A
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Malaisse
W J
WJ
D000818:Animals; D004777:Environment; D005260:Female; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D005632:Fructose; D005947:Glucose