Circulating glucagon. Plasma profiles and metabolism in health and disease.

JB Jaspan, AH Rubenstein - 1977 - cabidigitallibrary.org
JB Jaspan, AH Rubenstein
1977cabidigitallibrary.org
The patterns of immunoreactive glucagon (IRG) components are reviewed in normal
subjects and in patients with renal failure, diabetes mellitus, glucagonoma and other
conditions. The role of the kidneys and the liver in the metabolism of glucagon is discussed.
It is concluded that circulating IRG is heterogeneous, consisting of at least 4 fractions: A:
above 40 000 daltons; B: 9000 daltons; C: 3500 daltons; and D: below 2000 daltons. In
healthy subjects plasma IRG is distributed between the" A" and" C" peak components in …
Abstract
The patterns of immunoreactive glucagon (IRG) components are reviewed in normal subjects and in patients with renal failure, diabetes mellitus, glucagonoma and other conditions. The role of the kidneys and the liver in the metabolism of glucagon is discussed. It is concluded that circulating IRG is heterogeneous, consisting of at least 4 fractions: A: above 40 000 daltons; B: 9000 daltons; C: 3500 daltons; and D: below 2000 daltons. In healthy subjects plasma IRG is distributed between the "A" and "C" peak components in highly variable proportions. Small quantities of the "B" peak component may be present in normal plasma, but the values are too low to be measured by routine methods. Patients with chronic renal failure have high plasma glucagon values, with the appearance of 56 plus or minus 3% in the 9000-dalton fraction. Decreased responsiveness of that component accounts for the impaired suppression or stimulation of plasma IRG in uraemic patients in response to glucose or arginine challenge. The biological significance of fractions other than the 3500-dalton moiety is unknown. The 9000-dalton fraction may be a precursor, proglucagon, and may be an indicator of an underlying glucagonoma. Metabolism of glucagon occurs mainly in the liver and kidney. The liver extracts the 3500-dalton fraction but not the other components. The kidney metabolizes the 3500-dalton fraction (by glomerular filtration and peritubular uptake) and the 9000-dalton component (by peritubular uptake). The metabolic handling of pancreatic beta-cell and alpha-cell peptides is similar.
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