Cited by 303Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes and associated disorders

Insulin within islets is a physiologic glucagon release inhibitor

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Maruyama, H, Hisatomi, A, Orci, L, Grodsky, G M, Unger, R H·1984·Journal of Clinical Investigation

Abstract

To determine if glucagon secretion is under physiological control of intra-islet insulin, pancreata from normal rats were perfused at a 100 mg/dl glucose concentration with either guinea pig antiinsulin serum or normal guinea pig serum in a nonrecirculating system. Perfusion of antiserum was followed within 3 min by a significant rise in glucagon that reached peak levels three times the base-line values and assumed a hectic pattern that returned rapidly to base-line levels upon termination of the antiserum perfusion. Nonimmune guinea pig serum had no effect. To gain insight into the probable site of insulin neutralization, 125I-labeled human gamma-globulin was added to antiserum or nonimmune serum and perfused for 3 min. More than 83% of the radioactivity was recovered in the effluent within 3 min after termination of the infusion, and only 0.05 +/- 0.015% of the radioactivity injected was present in the pancreas 10 min after the perfusion. The maximal amount of insulin that could be completely bound to insulin antibody at a dilution and under conditions simulating those of the perfusion experiments was 20 mU/min. It is concluded that insulin maintains an ongoing restraint upon alpha cell secretion and in its absence causes hectic hypersecretion of glucagon. This restraint probably occurs largely in the intravascular compartment. Loss of this release-inhibiting action of insulin may account for initiation of hyperglucagonemia in insulin-deficient states.

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Research works printed but not linked: 2

  1. Samols, E., J. Tyler, and V. Marks. 1972. Glucagon-insulin interrelationships. In Glucagon. Molecular Physiology, Clinical and Therapeutic Implications. P. J. Lefebvre and R. H. Unger, editors. Pergamon Press Inc., Elmsford, NY. 151-174.
  2. Harris, V., G. R. Faloona, and R. H. Unger. 1979. Glucagon. In Methods of Hormone Radioimmunoassay. B. M. Jaffe and H. R. Behrman, editors. Academic Press, Inc., New York. 643-656.

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Authors
Maruyama, H., Hisatomi, A., Orci, L., Grodsky, G. M., & Unger, R. H.
Affiliations
  • University of Geneva (CH)
  • University of Texas Health Science Center at Dallas (US)
Venue
Journal of Clinical Investigation
Published
1984-12-01
Volume
74
Issue
6
Pages
2296-2299
ISSN
0021-9738 (ISSN-L)
OpenAlex
W1984541901
Cited by
303
References
17
Citations by year
2026: 3 · 2025: 1 · 2024: 5 · 2023: 5 · 2022: 1 · 2021: 15 · 2020: 10 · 2019: 9 · 2018: 11 · 2017: 12 · 2016: 14 · 2015: 10 · 2014: 15 · 2013: 6 · 2012: 8
FWCI
9.15
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (2r01am022150-07)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
insulin, glucagon secretion, pancreatic islets, alpha cells, hyperglucagonemia, insulin deficiency, hypersecretion
MeSH terms
Animals, Glucagon, Guinea Pigs, Insulin, Insulin Antibodies, Islets of Langerhans, Male, Perfusion, Time Factors, Rats

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