Hepatic metabolism of glucagon in the dog: contribution of the liver to overall metabolic disposal of glucagon
Abstract
The hepatic extraction (HE) of glucagon (G) and insulin (I) was measured in 27 dogs, using peripheral infusion of the hormones following elimination of endogenous secretion by pancreatectomy (Px) or somatostatin (S) infusion. HE(G) was 22.5 +/- 1.7%, and HE(I) was 45.1 +/- 3%. HE(G) in seven Px dogs was 27.9 +/- 4.2%, not significantly different from the value of 20.6 +/- 1.6% in 20 S-infused dogs, with corresponding values for HE(I) being 44.9 +/- 6 and 46.0 +/- 3.6%, respectively, suggesting that S does not affect HE of either hormone. HE of endogenous G (22.1 +/- 2.8%) was similar to that of exogenously infused G (19.1 +/- 1.9). HE(G) was nonsaturable in the physiologic and pathophysiologic range of plasma G levels, but there was evidence of saturability in the pharmacologic range. Comparison of simultaneously measured parameters of I and G metabolism indicated independence of the metabolic processes of these two islet hormones, despite distinct similarities in their overall patterns of metabolic disposal. Metabolic clearance rates (MCR) for G and I were 12.6 +/- 0.8 and 19.5 +/- 1.0 ml . kg-1 . min-1, while simultaneously measured hepatic HE rates were 4.2 +/- 0.3 and 8.1 +/- 0.6 ml . kg-1 . min-1, respectively. MCR(G) was independent of arterial G levels. Half-life of infused G and I was 5.5 +/- 0.5 and 4.1 +/- 0.3 min, respectively. The liver accounted for 34.7 +/- 2.4% of the MCR(G) and 42.0 +/- 2.9% of MCR(I). The liver is thus an important site for G removal. However…
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Because the glucagon antiserum crossreacts with species in addition to 3,500-dalton glucagon and somatostatin suppresses 3,500-dalton glucagon preferentially, biologically active glucagon was likely suppressed substantially.
“However, since the antiserum used crossreacts with species in addition to 3,500dalton glucagon (25), and somatostatin suppresses 3,500-dalton glucagon preferentially (26–28), biologically active glucagon was likely suppressed substantially.”
From Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man (1984) · cites this paper as [27]
Somatostatin preferentially suppresses the secretion of 3,500-D glucagon in dogs, a glucagonoma patient, and normal humans.
“Since somatostatin preferentially suppresses the secretion of 3,500-D glucagon in dogs (20, 21), a glucagonoma patient (22), and normal humans¹”
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- Authors
- Jaspan, J. B., Polonsky, K. S., Lewis, M., Pensler, J., Pugh, W., Moossa, A. R., & Rubenstein, A. H.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 1981-03-01
- Volume
- 240
- Issue
- 3
- Pages
- E233-E244
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2278625749
- Cited by
- 68
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2019: 1 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 4 · 2012: 2
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucagon, hepatic extraction, hepatic metabolism, insulin, metabolic clearance rate, somatostatin, pancreatic resection
- MeSH terms
- Animals, Dogs, Female, Glucagon, Hepatic Artery, Insulin, Liver, Male, Metabolic Clearance Rate, Portal Vein, Regional Blood Flow
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