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insulin clamp studies were performed with a 40 mU · m-2 · min-1 insulin infusion in the basal, post-absorptive, insulin-withdrawn state, before and during the last 3 h of a 72-h glucagon replacement-dose infusion (1.25 ng · kg-1 · min-1).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
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0022500004&doi=10.2337%2fdiab.35.5.556&partnerID=40&md5=136e45e8e04361aa10196de7afa4b932
Notes: Article -- Export Date: 18 August 2021 -- Source: Scopus -- MSK author Malayappa Jeevanandam's first name is misspelled on the original publication
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MSK Authors
  1. Murray F Brennan
    1059 Brennan
  2. Joseph G Fortner
    38 Fortner
  3. Daiva R. Bajorunas
    24 Bajorunas
  4. Malayappa Jeevanandam
    38 Jeevanandam
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