Glucagon Supports Postabsorptive Plasma Glucose Concentrations in Humans With Biologically Optimal Insulin Levels

OBJECTIVE Based on the premise that postabsorptive patients with type 1 diabetes receiving intravenous insulin in a dose that maintains stable euglycemia are receiving biologically optimal insulin replacement, we tested the hypothesis that glucagon supports postabsorptive plasma glucose concentrations in humans. RESEARCH DESIGN AND METHODS Fourteen patients with type 1 diabetes were studied after an overnight fast on up to five occasions. Insulin was infused intravenously to hold plasma glucose concentrations at ∼100 mg/dl (5.6 mmol/l) overnight and fixed from -60 to 240 min the following morning. From 0 through 180 min the patients also received 1) saline, 2) octreotide 30 ng · kg(-1) · min(-1) with growth hormone replacement or octreotide with growth hormone, plus 3) glucagon in doses of 0.5 ng · kg(-1) · min(-1), 4) 1.0 ng · kg(-1) · min(-1), and 5) 2.0 ng · kg(-1) · min(-1). RESULTS Compared with a mean ± SE of 98 ± 5 mg/dl (5.4 ± 0.3 mmol/l) at 180 min during saline, mean plasma glucose concentrations declined to 58 ± 1 mg/dl (3.2 ± 0.1 mmol/l) (P < 0.001) at 180 min during octreotide plus saline and were 104 ± 16 mg/dl (5.8 ± 0.9 mmol/l) (NS), 143 ± 13 mg/dl (7.9 ± 0.7 mmol/l) (P = 0.004), and 160 ± 15 mg/dl (8.9 ± 0.8 mmol/l) (P < 0.001) at 180 min during octreotide plus glucagon in doses of 0.5, 1.0, and 2.0 ng · kg(-1) · min(-1), respectively. CONCLUSIONS In the setting of biologically optimal insulin replacement, suppression of glucagon secretion with octreotide caused a progressive fall in plasma glucose concentrations that was prevented by glucagon replacement. These data document that glucagon supports postabsorptive glucose concentrations in humans.