Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance Journal Article

Authors: Bajorunas, D. R.; Dresler, C. M.; Horowitz, G. D.; McDermott, K.; Jeevanandam, M.; Fortner, J. G.; Brennan, M. F.
Article Title: Basal glucagon replacement in chronic glucagon deficiency increases insulin resistance
Abstract: To evaluate the role of glucagon in insulin-mediated glucose metabolism, we studied four men and four women, ranging in age from 30-73 yr (mean ± SEM, 54 ± 5) who had undergone complete pancreatic resection for cancer or chronic pancreatitis 16-58 mo previously. The patients had undetectable C-peptide levels and established lack of biologically active 3500 mol wt glucagon. Euglycemic insulin clamp studies were performed with a 40 mU · m-2 · min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng · kg-1 · min-1). In four patients, hepatic glucose production was determined by a primed-constant infusion of 3-[3H]glucose. Monocyte insulin-binding studies, pre- and postglucagon, were performed in all patients. The 72-h glucagon infusion, resulting in mean plasma glucagon levels of 124 ± 7 pg/ml, caused a significant rise in the mean plasma glucose level (249 ± 8 versus 170 ± 13 mg/dl preglucagon) and a sixfold increase in mean 24-h glucose excretion. Both with and without glucagon, euglycemic hyperinsulinemia achieved identical and complete suppression of hepatic glucose production. The mean glucose utilization rate (4.70 ± 0.36 mg · kg-1 · min-1 preglucagon) was significantly decreased by glucagon replacement (3.83 ± 0.31 mg · kg-1 · min-1, P < 0.02). Mean glucose clearance was also diminished with glucagon (4.49 ± 0.32 versus 5.73 ± 0.45 ml · kg-1 · min-1 preglucagon, P < 0.02). After glucagon administration, no significant change in the percent specific binding of insulin to monocytes could be demonstrated. These data support a role of physiologic concentrations of glucagon in the modulation of peripheral tissue glucose utilization.
Keywords: unclassified drug; human cell; pancreas cancer; pancreas resection; pancreas; drug resistance; drug receptor binding; drug mechanism; diagnosis; pancreatitis; diabetes mellitus; insulin; insulin resistance; drug blood level; radioisotope; glucose tolerance test; intravenous drug administration; pharmacokinetics; hormone substitution; drug urine level; oral drug administration; human experiment; endocrine system; etiology; glucose utilization; glucagon; c peptide; human; priority journal; article; glucagon deficiency; blood and hemopoietic system; insulin i 125; glucose h 3
Journal Title: Diabetes
Volume: 35
Issue: 5
ISSN: 0012-1797
Publisher: American Diabetes Association  
Date Published: 1986-05-01
Start Page: 556
End Page: 562
Language: English
DOI: 10.2337/diab.35.5.556
PROVIDER: scopus
PUBMED: 3514331
Notes: Article -- Export Date: 18 August 2021 -- Source: Scopus; Acknowledgments: We are indebted to Dr. Jonathan Jaspan, University of Chicago, who performed the glucagon chromatographic profiles and assayed the glucagon plasma levels in these patients. Free-insulin concentrations were kindly performed by Dr. S. Edwin Fineberg, Indiana University. We thank Gail Kuhlman for technical assistance and Patty Bradshaw and Susan Ruffini for artistic and secretarial help. We are especially grateful to the nursing staff of the Rockefeller University Clinical Research Center for care of our patients.
Citation Impact
MSK Authors
  1. Murray F Brennan
    1002 Brennan
  2. Joseph G Fortner
    35 Fortner