Insulin response to glucagon with or without tolbutamide in normal and diabetic subjects

In order to investigate insulin response to glucagon, eight normal subjects and thirty diabetic patients were studied. According to fasting blood glucose, diabetic patients were classified into three groups; mild, moderate and severe. An oral glucose tolerance test, a glucagon test and a tolbutamide-glucagon test were performed at intervals of several days. In the glucose tolerance test, insulin response was reduced in the patients with moderate or severe diabetes. Plasma insulin increased and reached a peak 3 min after glucagon injection (glucagon 1) in the normal controls (66.1 +/- 9.9 microunits/ml), while plasma insulin response to glucagon 1 was reduced in the three diabetic groups (35.8 +/- 7.3, 33.2 +/- 9.7 and 22.9 +/- 5.0 microunits/ml, respectively). In the normal subjects glucagon injected 60 min after tolbutamide (glucagon 2) caused a rise in insulin (72.0 +/- 4.9 microunits/ml). In the diabetic groups, glucagon 2 caused a reduced response of plasma insulin (38.6 +/- 8.9, 49.5 +/- 17.4 and 34.8 +/- 11.3 microunits/ml, respectively). Glucagon with or without tolbutamide produced a far greater maximal response of plasma insulin in all the diabetic groups than in the normal subjects, while glucose produced a not significantly different increment of plasma insulin between the normal subjects and the mild diabetics. The present study demonstrates the glucagon injection with or without tolbutamide could clearly discriminate the insulin response in diabetics from that in normal subjects.