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Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic beta-cells

Diakogiannaki, Eleftheria, Dhayal, Shalinee, Childs, Caroline E., Calder, Philip C., Welters, Hannah J. and Morgan, Noel G. (2007) Mechanisms involved in the cytotoxic and cytoprotective actions of saturated versus monounsaturated long-chain fatty acids in pancreatic beta-cells Journal of Endocrinology, 194, (2), pp. 283-291. (doi:10.1677/JOE-07-0082).

Record type: Article

Abstract

Long-chain saturated and monounsaturated fatty acids differ in their propensity to induce beta-cell death in vitro with palmitate (C16:0) being cytotoxic, whereas palmitoleate (C16:1n-7) is cytoprotective. We now show that this cytoprotective capacity extends to a poorly metabolised C16:1n-7 derivative, methyl-palmitoleate (0.25 mM palmitate alone: 92 +/- 4% death after 18 h; palmitate plus 0.25 mM methyl-palmitoleate: 12 +/- 2%; P < 0.001). Palmitoleate and its methylated derivative also acted as mitogens in cultured beta-cells (5-bromo-2-deoxyuridine incorporation - control: 0.15 +/- 0.01 units; 0.25 mM palmitoleate: 0.22 +/- 0.01 units; P < 0.05). It has been proposed that alterations in neutral lipid synthesis (particularly triacylglycerol (TAG) formation) might mediate the differential responses to saturated and unsaturated fatty acids and we have examined this proposition. Palmitate and palmitoleate both promoted beta-cell phospholipid remodelling and increased TAG formation (control: 0.9 +/- 0.1 nmol TAG/10(6) cells; 0.25 mM palmitate: 1.55 +/- 0.07; 0.25 mM palmitoleate: 1.4 +/- 0.05; palmitate plus palmitoleate: 2.3 +/- 0.1). By contrast, methyl-palmitoleate failed to influence TAG levels (0.25 mM methyl-palmitoleate alone: 0.95 +/- 0.06 nmol TAG/10(6) cells; methyl-palmitoleate plus palmitate: 1.5 +/- 0.05) or its fatty acid composition in beta-cells exposed to palmitate. The results suggest that monounsaturated fatty acids can promote cell viability and mitogenesis by a mechanism that does not require their metabolism and is independent of alterations in TAG formation.

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Published date: August 2007
Organisations: Faculty of Medicine, Medicine

Identifiers

Local EPrints ID: 61064
URI: http://eprints.soton.ac.uk/id/eprint/61064
PURE UUID: f1ebb9b8-ed31-4c70-9202-5700e8f7fdc6
ORCID for Caroline E. Childs: ORCID iD orcid.org/0000-0001-6832-224X

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Date deposited: 24 Sep 2008
Last modified: 17 Jul 2017 14:22

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Contributors

Author: Eleftheria Diakogiannaki
Author: Shalinee Dhayal
Author: Hannah J. Welters
Author: Noel G. Morgan

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