title: Intracellular depletion of insulin by oleate is due to an inhibited synthesis and not to an increased secretion.
abstract: In the polyclonal rat pancreatic beta-cell line INS-1, immunoreactive insulin (IRI, insulin and its precursors) and C-peptide (surrogate marker for mature insulin) were quantified after a 1-h incubation at 16.7 mM glucose with or without oleate. Oleate caused a 20% decrease (P <or= 0.01) and a shift towards mature insulin (P <or= 0.01) in intracellular IRI. As IRI secretion was significantly (P <or= 0.01) diminished in the presence of oleate at hyperglycemic conditions the loss of intracellular IRI had to be due to other reasons which was then examined by focussing on newly synthesized, radiolabelled IRI*. Thereby, oleate caused a 50% decrease in newly synthesized intracellular IRI* (P <or= 0.01) and-contrary to the findings in complete intracellular IRI-a shift towards immature insulin precursors. Taken together, exposure of INS-1 cells to oleate induces an intracellular lack of uncompletely processed IRI. This is due to an inhibited biosynthetic supply which can not compensate for intracellular IRI-degradation and (to a neglible extent) for insulin secretion.
authors.affiliation: Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany. cornelius.bollheimer@klinik.uni-regensburg.de
authors.forename: L C
authors.initials: LC
authors.lastname: Bollheimer
authors.forename: T M
authors.initials: TM
authors.lastname: Kestler
authors.forename: J
authors.initials: J
authors.lastname: Michel
authors.forename: R
authors.initials: R
authors.lastname: Buettner
authors.forename: J
authors.initials: J
authors.lastname: Schölmerich
authors.forename: K D
authors.initials: KD
authors.lastname: Palitzsch
mesh_terms: D000818:Animals; D012634:Bodily Secretions / Q000187:drug effects; D002096:C-Peptide / Q000378:metabolism; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D007328:Insulin / Q000276:immunology / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D051381:Rats
chemical_list: D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D011500:Protein Synthesis Inhibitors; D019301:Oleic Acid