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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 systems, 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.

To determine if the glucoregulatory hormones, insulin and glucagon, are altered with aging inman, 44 healthy volunteers, 22-81 yr of age, were evaluted by measurement of basal levels of glucose, insulin, and glucagon in relationship to their fat mass. In addition, the secretory capacities of the alpha and beta cells were assessed by measurement of the amounts of glucagon and insulin released after intravenous administration of glucose and arginine, respectively. Although no significant differences in weight could be distinguished longitudinally, the percentage adiposity was found to increase with age. Basal concentrations of glucose, glucagon, and insulin were not appreciably altered as a function of advancing years. After intravenous glucose, the glucose disappearance rate (Kg) was significantly slower in the elderly in comparison with the young, yet no differences in glucose-induced release were found. Similarly, insulin responses after arginine infusion between young and old were indistinguishable. The release of glucagon in response to arginine infusion was not perceptibly altered during aging. Thus, despite a decline in Kg with advanging age in this healthy population, gross changes in insulin and glucagon release were not apparent. We infer from bese data that decreased carbohydrate tolerance accompanying aging in some populations may be due to factors other than abnormalities in secretion of insulin and glucagon.