Environmental modulation of d-fructose insulinotropic action

Abstract

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 μmol/l), theophylline (1.4 mmol/l), cytochalasin B (21 μmol/l) and glibenclamide (5 μmol/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.