Effects of portal injection of 2,5-anhydro-D-mannitol on pancreatic hormone responses to exercise in rats

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) has been shown to act specifically in liver by decreasing liver ATP and by blocking glycogenolys is and gluconeogenesis. The present investigation was designed to determine the effects of the administration of 2,5-AM on pancreatic hormone response s during a situation of increased energy demand such as physical exercise, and by comparison to the resting response, to test the possibility that the hormonal effects of 2,5-AM during exercise may be dissociated from a decre ase in blood glucose levels. Adrenodemedullated rats were injected intrapor tally with a dose of 200 mg/kg of 2,5-AM (50 mg/ml) or by an equivalent vol ume of saline (0.9% NaCl) before being submitted to a 30-min treadmill run (26 m/min, 0 % grade). Administration of 2,5-AM at rest resulted in a signi ficant (P < 0.05) decrease of plasma glucose and insulin levels and an incr ease in beta-hydroxybutyrate concentrations. During exercise, administratio n of 2,5-AM, as compared to resting values, resulted in a larger decrease i n glucose, a similar decrease in insulin, and a much larger increase in glu cagon, glucagon/insulin molar ratio, and P-hydroxybutyrate concentrations. It is concluded that exercise amplifies some of the metabolic and hormonal effects of 2,5-AM, and that these effects cannot all be explained by the de crease in blood glucose levels.