Effect of glucose on production and release of proinsulin conversion products by cultured human islets

Isolated human islets were examined for the rates of conversion and release of newly formed (pro)insulin-like peptides. The rate of proinsulin (PI) conversion was 2-fold slower in human beta-cells (t(1/2) = 50 min) than in rat beta-cells (t(1/2) = 25 min). During the first hour following labeling of...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 1998-04, Vol.83 (4), p.1234-1238
Main Authors: ZAMBRE, Y, ZHIDONG LING, XUE HOU, FORIERS, A, VAN DEN BOGAERT, B, VAN SCHRAVENDIJK, C, PIPELEERS, D
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cells, Cultured
Endocrine pancreas
Fundamental and applied biological sciences. Psychology
Glucose - pharmacology
Hormones. Régulation
Humans
Islets of Langerhans - drug effects
Islets of Langerhans - metabolism
Proinsulin - biosynthesis
Proinsulin - metabolism
Rats
Vertebrates: endocrinology
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Summary:Isolated human islets were examined for the rates of conversion and release of newly formed (pro)insulin-like peptides. The rate of proinsulin (PI) conversion was 2-fold slower in human beta-cells (t(1/2) = 50 min) than in rat beta-cells (t(1/2) = 25 min). During the first hour following labeling of newly synthesized proteins, PI represented the main newly formed hormonal peptide in the medium; its release was stimulated 2-fold over the basal level by 20 mmol/L glucose. During the second hour, newly synthesized hormone was mainly released as insulin, with 10- to 20-fold higher rates at 20 mmol/L glucose. Prolonged preculture of the islets at 20 mmol/L glucose did not delay PI conversion, but markedly increased the release of newly formed PI, des(31,32)-PI, and insulin at both low and high glucose levels. Our data demonstrate that 1) the release of PI provides an extracellular index for the hormone biosynthetic activity of human beta-cells; 2) an acute rise in glucose exerts a stronger amplification of the release of converted hormone than in that of nonconverted hormone; and 3) prolonged exposure to high glucose levels results in an elevated basal release of converted and nonconverted PI; this elevation is not associated with a delay in PI conversion, but is attributed to the hyperactivated state of the human beta-cell population, which was recently found to be responsible for an elevation in basal rates of hormone synthesis. These in vitro observations on human beta-cells provide a possible explanation for the altered circulating (pro)insulin levels measured in nondiabetic and noninsulin-dependent diabetic subjects.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.83.4.1234