Glucagon metabolism in man, studies on the metabolic clearance rate and the plasma acute disappearance time of glucagon in normal and diabetic subjects

To investigate further the "hyperglucagonaemia" of diabetes mellitus, the metabolic clearance rate (MCR) and acute disappearance time (t1/2) of unlabelled pancreatic glucagon were estimated in 9 normal subjects and 7 insulin-dependent diabetics, using a constant infusion technique. The mean MCR (+/-SE) was similar for both groups (control: 9.0 +/- 0.6; diabetics: 11.4 +/- 1.0 ml/kg/min). The MCR was not influenced by the concentration of glucagon at the time of plateau, and the exogenous hormone appeared to be handled similarly to endogenous glucagon. On the other hand, t1/2 calculated from the fractional decay rate of glucagon from plateau was significantly prolonged in the diabetics (t1/2 6.6 +/- 0.5 min) compared with the control group (t1/2 4.8 +/- 0.2 min, P less than 0.01). Furthermore, there was no correlation between MCR and t1/2, for the control, diabetic, or combined group. It therefore appears that the MCR of glucagon is similar in normal and diabetic subjects. However, since the acute disappearance time (t1/2) of glucagon is not identical in these two groups, it appears that the kinetics of the overall in vivo metabolism of pancreatic glucagon are not similar in diabetic and control subjects.