Heterogeneity and compartmental properties of insulin storage and secretion in rat islets

Journal Article · Mon Mar 01 04:00:00 EST 1982 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI110481· OSTI ID:5310602

Gold, G; Landahl, H D; Gishizky, M L; Grodsky, G M

To investigate compartmental properties of insulin storage and secretion, isolated rat islets were used for pulse-labeling experiments, after which proinsulin and insulin were purified rigorously. Processing of proinsulin to insulin neared completion by 3 h without additional loss of either radioactive peptide by cellular or extracellular proteolysis. The amount of labeled hormone rapidly diminished in islets; it was secreted at a higher fractional rate than immunoreactive insulin, resulting in secreted insulin's having a higher specific activity than the average cellular insulin. Newly synthesized insulin, therefore, was secreted preferentially. Changes in the specific activity of secreted and cellular insulin with time were consistent with changes predicted for islets containing 33% of their total insulin in a glucose-labile compartment. Predictions were based on steady-state analysis of a simple storage-limited representation of B cell function. Islets from either the dorsal or ventral part of the pancreas also contained 33% of their total insulin in a glucose-labile compartment. The same compartment was mobilized by 20 mM glucose, 50 mM potassium + 2 mM glucose, or 20 MM glucose + 1 mM 3-isobutylmethylxanthine as indicated by the specific activity ratio of secreted vs. cellular insulin, even though average secretion rates with these stimuli differed by more than threefold. In the absence of calcium, the effectiveness of 20 mM glucose as a secretagogue declined markedly, and the older stored insulin was preferentially mobilized because secreted insulin had a lower rather than a higher specific activity than cellular insulin. Results provide insight into the mechanisms of nonrandom mobilization and secretion of insulin form the B cell.

• Research Organization: Department of Biochemistry and Biophysics, University of California, San Francisco
• OSTI ID: 5310602
• Journal Information: J. Clin. Invest.; (United States), Journal Name: J. Clin. Invest.; (United States) Vol. 69:3; ISSN JCINA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
BIOCHEMICAL REACTION KINETICS
HORMONES
INSULIN
KINETICS
LABELLED COMPOUNDS
MAMMALS
METABOLISM
PEPTIDE HORMONES
RATS
REACTION KINETICS
RODENTS
VERTEBRATES