Metabolic modulation by concomitant administration of insulin and glucagon in pancreatectomy patients

The metabolic kinetics after a total pancreatectomy, especially the postoperative loss of pancreatic endocrine function including insulin and glucagon secretions, remain unexplored. We examined the metabolic status of patients after a total pancreatectomy under insulin control and the effects of glucagon administration on metabolic kinetics.

The metabolic assessments of 11 patients who had undergone total pancreatectomy were performed using indirect calorimetry with blood amino acid and lipid analysis in the following three metabolic conditions: 1) under conventional insulin control alone, 2) when a pharmacologically active amount of glucagon was administered, and 3) when an additional amount of insulin was administered concomitantly to attain the insulin/glucagon molar ratio in the serum similar to the physiological value.

Under conventional insulin control alone, the level of calorigenesis from proteins was decreased mainly due to an impairment in the utilization of glycogenic amino acids. Furthermore, carbohydrates were not sufficiently utilized, and lipid metabolism was increased as a result of the reduced lipid catabolism. When a pharmacologically active amount of glucagon was administered, the utilization of glycogenic amino acids and lipids increased. However, the utilization of carbohydrates was slightly reduced. When an additional amount of insulin was administered, an increased utilization of protein was observed. At the same time, marked improvement was observed in the utilization of carbohydrates which was reduced in 1) and 2) indicated above. Furthermore, the utilization of lipids in calorigenesis was not reduced, but it was reduced in lipid catabolism.

The above findings indicate the importance of administering insulin and glucagon concomitantly and maintaining the blood insulin/glucagon ratio at a level similar to the physiological value regardless of the administered dosages of these two hormones in order to improve the energy and nutritional metabolism following a total pancreatectomy.