Straub SG, Sharp GW.Inhibition of insulin secretion by
cerulenin might be due to impaired glucose metabolism.
Diabetes Metab Res Rev. 2006 May 16
The Department of Molecular Medicine, College of Veterinary
Medicine, Cornell University, Ithaca, NY 14853, USA.
sgs4@cornell.edu
Cerulenin, an inhibitor of protein acylation, has been used
as a tool to study the potential role of protein acylation in a
variety of activities in different cells, and in
stimulus-secretion coupling in pancreatic islets and clonal
beta-cells. METHODS: In the present study we investigated its
effects on stimulated insulin secretion, glucose metabolism and
utilization, oxygen consumption and ATP levels. RESULTS: In
isolated rat pancreatic islets, cerulenin pre-treatment (100
microM) inhibited insulin secretion in response to glucose, and
to the non-hydrolysable analogue of leucine, aminobicyclo-[2,2,1]heptane-2-carboxylic
acid (BCH). These data are in accord with the hypothesis that
protein acylation could be involved in the stimulation of
insulin secretion. However, we also found that cerulenin
profoundly decreased glucose oxidation, glucose utilization,
oxygen consumption and ATP levels. Consequently, decreased
metabolism provides an alternative mechanism to inhibition of
protein acylation that could explain the inhibition of insulin
secretion by cerulenin. CONCLUSIONS: Inhibition of insulin
secretion by cerulenin can no longer be taken as evidence in
favour of a role for protein acylation in the control of insulin
release. As protein acylation is known to be involved in the
normal functioning of proteins in stimulus-secretion coupling
and exocytosis, more direct approaches to understand its role(s)
are required.
PMID: 16705622
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