The metabolic effects of chronic hyperglucagonaemia

A subject with a benign glucagonoma was studied before and after complete resection of his pancreatic tumour. Studies were undertaken pre- and post-operatively to determine the effects of chronic hyperglucagonaemia on glucose tolerance and glucose kinetics both in the fasting state and during physiological insulin infusions, employing the [3H]-3-glucose technique. In addition the plasma cyclic AMP response to an acute infusion of glucagon was studied pre- and post-operatively. The basal immunoreactive glucagon levels pre- and post-operatively were 10492 +/- 1296 and 149 +/- 15 pg/ml respectively. Pre- and post-operative oral glucose tolerance tests did not differ but were abnormal. Pre-operatively basal hepatic glucose production was normal and it was suppressed rapidly by the low dose insulin infusion, despite continuing hyperglucagonaemia. The metabolic clearance rate of glucose was slightly reduced. There was no plasma cyclic AMP response to a glucagon infusion, suggesting down-regulation of the glucagon receptor by the chronic hyperglucagonaemia. Post-operatively the hepatic glucose production and clearance rate of glucose fell, whereas the plasma cyclic AMP responses to the glucagon infusion reverted to a normal pattern. It is concluded that chronic hyperglucagonaemia is not a major factor in the development of the glucose intolerance, but it may lead to down-regulation of the biological action of glucagon.