title: Effect of glucose on production and release of proinsulin conversion products by cultured human islets.
abstract: 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.
authors.affiliation: Diabetes Research Center and the Department of Pharmaceutical and Biochemical Analysis, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Y
authors.initials: Y
authors.lastname: Zambre
authors.forename: Z
authors.initials: Z
authors.lastname: Ling
authors.forename: X
authors.initials: X
authors.lastname: Hou
authors.forename: A
authors.initials: A
authors.lastname: Foriers
authors.forename: B
authors.initials: B
authors.lastname: Van Den Bogaert
authors.forename: C
authors.initials: C
authors.lastname: Van Schravendijk
authors.forename: D
authors.initials: D
authors.lastname: Pipeleers
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats
chemical_list: D011384:Proinsulin; D005947:Glucose