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.


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.
Cooperberg
Benjamin A
BA
Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, USA.
Cryer
Philip E
PE
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005934:Glucagon / Q000097:blood* / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007408:Intestinal Absorption; D008297:Male; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon