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 glycogenolysis and gluconeogenesis. The present investigation was designed to determine the effects of the administration of 2,5-AM on pancreatic hormone responses 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 decrease in blood glucose levels. Adrenodemedullated rats were injected intraportally with a dose of 200 mg/kg of 2,5-AM (50 mg/ml) or by an equivalent volume 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 significant (P < 0.05) decrease of plasma glucose and insulin levels and an increase in beta-hydroxybutyrate concentrations. During exercise, administration of 2,5-AM, as compared to resting values, resulted in a larger decrease in glucose, a similar decrease in insulin, and a much larger increase in glucagon, glucagon/insulin molar ratio, and beta-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 decrease in blood glucose levels.