Inhibition of insulin secretion by cerulenin might be due to impaired glucose metabolism

Abstract

Background 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 β-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 µM) 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. Copyright © 2006 John Wiley & Sons, Ltd.