The failure of aminophylline to modulate glucagon release in man

There are conflicting results regarding the impact of cyclic AMP on pancreatic glucagon release. The effect of aminophylline, a phosphodiesterase inhibitor, on glucagon secretion was studied in four non-obese, non-diabetic, healthy young male volunteers. The subjects received separate infusions of: 1) aminophylline; 2) aminophylline and propranolol; 3) arginine; 4) aminophylline and arginine; 5) insulin; 6) aminophylline and insulin; and 7) aminophylline and isoproterenol. Aminophylline not only failed to alter glucagon levels but also did not affect the glucagon responses observed after arginine and insulin-induced hypoglycemia. The concurrent infusion of isoproterenol and aminophylline also failed to cause a glucagon response. Although glucagon release has been evoked by cyclic AMP in some in vitro system, administration of aminophylline to human subjects does not enhance secretion. These results indirectly suggest that cyclic AMP is of little importance in the control of glucagon secretion in man, though the effects of aminophylline at the cellular level may be complex.