Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells)

Jude T. Deeney, Jesper Gromada, Marianne Høy, Hervør L. Olsen, Christopher J. Rhodes, Marc Prentki, Per Olof Berggren, Barbara E. Corkey

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Non-insulin-dependent diabetes mellitus is associated with, in addition to impaired insulin release, elevated levels of free fatty acids (FFA) in the blood. Insulin release is stimulated when β-cells are acutely exposed to FFA, whereas chronic exposure may inhibit glucose-induced insulin secretion. In the present study we investigated the direct effects of long chain acyl- CoA (LC-CoA), the active intracellular form of FFA, on insulin exocytosis. Palmitoyl-CoA stimulated both insulin release from streptolysin-O- permeabilized HIT cells and fusion of secretory granules to the plasma membrane of mouse pancreatic β-cells, as measured by cell capacitance. The LC-CoA effect was chain length-dependent, requiring chain lengths of at least 14 carbons. LC-CoA needed to be present to stimulate insulin release, and consequently there was no effect following its removal. The stimulatory effect was observed after inhibition of protein kinase activity and in the absence of ATP, even though both kinases and ATP, themselves, modulate exocytosis. The effect of LC-CoA was inhibited by cerulenin, which has been shown to block protein acylation. The data suggest that altered LC-CoA levels, resulting from FFA or glucose metabolism, may act directly on the exocytotic machinery to stimulate insulin release by a mechanism involving LC-CoA protein binding.

Original languageEnglish
Pages (from-to)9363-9368
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number13
DOIs
StatePublished - Mar 31 2000
Externally publishedYes

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Acyl Coenzyme A
Exocytosis
Insulin-Secreting Cells
Insulin
Nonesterified Fatty Acids
Chain length
Cerulenin
Adenosine Triphosphate
Palmitoyl Coenzyme A
Glucose
Acylation
Cell Fusion
Secretory Vesicles
Cell membranes
Medical problems
Protein Binding
Metabolism
Protein Kinases
Type 2 Diabetes Mellitus
Machinery

ASJC Scopus subject areas

  • Biochemistry

Cite this

Deeney, J. T., Gromada, J., Høy, M., Olsen, H. L., Rhodes, C. J., Prentki, M., ... Corkey, B. E. (2000). Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells). Journal of Biological Chemistry, 275(13), 9363-9368. https://doi.org/10.1074/jbc.275.13.9363

Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells). / Deeney, Jude T.; Gromada, Jesper; Høy, Marianne; Olsen, Hervør L.; Rhodes, Christopher J.; Prentki, Marc; Berggren, Per Olof; Corkey, Barbara E.

In: Journal of Biological Chemistry, Vol. 275, No. 13, 31.03.2000, p. 9363-9368.

Research output: Contribution to journalArticle

Deeney, JT, Gromada, J, Høy, M, Olsen, HL, Rhodes, CJ, Prentki, M, Berggren, PO & Corkey, BE 2000, 'Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells)', Journal of Biological Chemistry, vol. 275, no. 13, pp. 9363-9368. https://doi.org/10.1074/jbc.275.13.9363
Deeney, Jude T. ; Gromada, Jesper ; Høy, Marianne ; Olsen, Hervør L. ; Rhodes, Christopher J. ; Prentki, Marc ; Berggren, Per Olof ; Corkey, Barbara E. / Acute stimulation with long chain acyl-CoA enhances exocytosis in insulin-secreting cells (HIT T-15 and NMRI β-cells). In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 13. pp. 9363-9368.
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