DECREASED HEPATIC GLUCAGON-RESPONSES IN TYPE-1 (INSULIN-DEPENDENT) DIABETES-MELLITUS

The effect of glucagon infusion on hepatic glucose production during euglycaemia was evaluated in seven Type 1 (insulin-dependent) diabetic patients and in ten control subjects. In the diabetic subjects normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin and glucose infusion. During the study endogenous insulin secretion was suppressed by somatostain (450-mu-g/h) and replaced by insulin infusion (0.15 mU.kg-1.min-1). H-3-glucose was infused for isotopic determination of glucose turnover. Plasma glucose was clamped at 5 mmol/l for 2 h 30 min and glucagon (1.5 ng.kg-1.min-1) was then infused for the following 3 h. Hepatic glucose production and glucose utilisation were measured during the first, second and third hour of the glucagon infusion. Basal hepatic glucose production (just prior to glucagon infusion) was similar in diabetic (1.2 +/- 0.3 mg.kg-1.min-1) and control (1.6 +/- 0.1 mg.kg-1.min-1) subjects. In diabetic patients hepatic glucose production rose slowly to 2.1 +/- 0.5 mg.kg-1.min-1 during the first hours of glucagon infusion and stabilized at this level (2.4 +/- 0.5 mg.kg-1.min-1) in the third hour. In control subjects hepatic glucose production increased sharply to higher levels than in the diabetic subjects (3.4 +/- 0.3 mg.kg-1.min-1) during the first and second hour of glucagon infusion (p < 0.05) and then gradually fell (2.9 +/- 0.4 mg.kg-1.min-1) during the third hour. In conclusion, when stimulated with glucagon at a physiologic plasma concentration diabetic patients had 1) an overall reduced hepatic glucose production response and 2) an abnormal sluggish response pattern. These abnormalities may imply inappropriate counter-regulation following a hypoglycaemic episode.