Glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.
OBJECTIVE
Given the interest in glucagon antagonism as a potential treatment of diabetes, we tested the hypothesis that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.


METHODS
Following preliminary studies that indicated that a peripheral intravenous insulin dose of 0.1 mU x kg(-1) x min(-1) (lower than those used previously) provides basal insulin replacement and that a glucagon dose of 1.0 ng x kg(-1) x min(-1) underreplaces basal glucagon, we infused the somatostatin analog octreotide (30 ng x kg(-1) x min(-1)) (with growth hormone replacement) over 4 h in 14 healthy adults on four separate occasions to produce endogenous insulin and glucagon deficiency with 1) saline (combined insulin and glucagon deficiency), 2) insulin replacement (isolated glucagon deficiency), 3) partial glucagon replacement (insulin and partial glucagon deficiency), and 4) insulin and partial glucagon replacement (partial glucagon deficiency).


RESULTS
During combined insulin and glucagon deficiency, glucose production decreased and then increased, and mean (+/-SE) plasma glucose decreased from 83 +/- 1 to 63 +/- 2 mg/dl at 60 min and then increased to 89 +/- 3 mg/dl at 240 min. During isolated glucagon deficiency, plasma glucose decreased to hypoglycemic levels and was 55 +/- 2 mg/dl at 240 min (P < 0.0001 vs. combined insulin and glucagon deficiency). Partial glucagon replacement raised plasma glucose to higher levels (P = 0.0469) during insulin deficiency and to higher levels (P = 0.0090) during insulin replacement.


CONCLUSIONS
These three findings provide direct evidence that glucagon, in concert with insulin, supports the postabsorptive plasma glucose concentration in humans.
Breckenridge
Suzanne M
SM
Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cooperberg
Benjamin A
BA
Arbelaez
Ana Maria
AM
Patterson
Bruce W
BW
Cryer
Philip E
PE
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood / Q000494:pharmacology*; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D019382:Human Growth Hormone; D005934:Glucagon; D005947:Glucose; D015282:Octreotide