| Autor: |
Yasmeeni Zambre, Zhidong Ling, Hou, X., Andre Foriers, Den Bogaert, B., Christiaan Van Schravendijk, Daniel Pipeleers |
| Přispěvatelé: |
Toxicology, Dermato-cosmetology and Pharmacognosy, Vrije Universiteit Brussel |
| Rok vydání: |
1998 |
| Předmět: |
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| Zdroj: |
Vrije Universiteit Brussel |
| ISSN: |
0021-972X |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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