A novel role for somatostatin in the survival of mouse pancreatic beta cells

Erin L. Damsteegt, Zoheb Hassan, Nirun V. Hewawasam, Kittiwadee Sarnsamak, Peter M. Jones, Astrid C. Hauge-Evans*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Background/Aims: Cross-talk between different pancreatic islet cell types regulates islet function and somatostatin (SST) released from pancreatic delta cells inhibits insulin secretion from pancreatic beta cells. In other tissues SST exhibits both protective and pro-apoptotic properties in a tissue-specific manner, but little is known about the impact of the peptide on beta cell survival. Here we investigate the specific role of SST in the regulation of beta cell survival in response to physiologically relevant inducers of cellular stress including palmitate, cytokines and glucose. Methods: Pancreatic MIN6 beta cells and primary mouse islet cells were pre-treated with SST with or without the Gi/o signalling inhibitor, pertussis toxin, and exposed to different cellular stress factors. Apoptosis and proliferation were assessed by measurement of caspase 3/7 activity, TUNEL and BrdU incorporation, respectively, and expression of target genes was measured by qPCR. Results: SST partly alleviated upregulation of cellular stress markers (Hspa1a and Ddit3) and beta cell apoptosis in response to factors such as lipotoxicity (palmitate), pro-inflammatory cytokines (IL1β and TNFα) and low glucose levels. This effect was mediated via a Gi/o protein-dependent pathway, but did not modify transcriptional upregulation of the specific NFκB-dependent genes, Nos2 and Ccl2, nor was it associated with transcriptional changes in SST receptor expression. Conclusion: Our results suggest an underlying protective effect of SST which modulates the beta cell response to ER stress and apoptosis induced by a range of cellular stressors associated with type 2 diabetes.

Original languageEnglish
Pages (from-to)486-502
Number of pages17
JournalCellular Physiology and Biochemistry
Volume52
Issue number3
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Beta cell survival
  • Cellular stress
  • Intra-islet communication
  • Lipotoxicity
  • Somatostatin
  • Type 2 diabetes

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