A Novel Role for Somatostatin in the Survival of Mouse Pancreatic Beta Cells.

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Abstrakt

Tytuł:: A Novel Role for Somatostatin in the Survival of Mouse Pancreatic Beta Cells.
Autorzy:: Damsteegt EL; Health Science Research Group, Department of Life Sciences, University of Roehampton, London, UK.
Hassan Z; Department of Diabetes, School of Life Course Sciences, King's College London, London, UK.
Hewawasam NV; Health Science Research Group, Department of Life Sciences, University of Roehampton, London, UK.
Sarnsamak K; Health Science Research Group, Department of Life Sciences, University of Roehampton, London, UK.
Jones PM; Department of Diabetes, School of Life Course Sciences, King's College London, London, UK.
Hauge-Evans AC; Health Science Research Group, Department of Life Sciences, University of Roehampton, London, UK, .
Źródło:: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2019; Vol. 52 (3), pp. 486-502. Date of Electronic Publication: 2019 Mar 15.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: 2019- : Düsseldorf, Germany : Cell Physiol Biochem Press GmbH & Co KG
Original Publication: Basel ; New York : S. Karger, 1991-2018.
MeSH Terms:: Cell Proliferation/*drug effects
Glucose/*antagonists & inhibitors
Insulin-Secreting Cells/*drug effects
Islets of Langerhans/*drug effects
Pertussis Toxin/*antagonists & inhibitors
Somatostatin/*pharmacology
Animals ; Apoptosis/drug effects ; Caspase 3/genetics ; Caspase 3/metabolism ; Caspase 7/genetics ; Caspase 7/metabolism ; Cell Line ; Chemokine CCL2/genetics ; Chemokine CCL2/metabolism ; Gene Expression Regulation ; Glucose/pharmacology ; HSP70 Heat-Shock Proteins/genetics ; HSP70 Heat-Shock Proteins/metabolism ; Insulin-Secreting Cells/cytology ; Insulin-Secreting Cells/metabolism ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/pharmacology ; Islets of Langerhans/metabolism ; Male ; Mice ; Mice, Inbred ICR ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/metabolism ; Palmitic Acid/antagonists & inhibitors ; Palmitic Acid/pharmacology ; Pertussis Toxin/pharmacology ; Tissue Culture Techniques ; Transcription Factor CHOP/genetics ; Transcription Factor CHOP/metabolism ; Tumor Necrosis Factor-alpha/antagonists & inhibitors ; Tumor Necrosis Factor-alpha/pharmacology
Grant Information:: BDA: 10/0003980 UK RD Lawrence Fellowship Grant, Diabetes UK; UK Equipment Grant, Society for Endocrinology
Contributed Indexing:: Keywords: Beta cell survival; Cellular stress; Intra-islet communication; Lipotoxicity; Somatostatin; Type 2 diabetes
Substance Nomenclature:: 0 (Ccl2 protein, mouse)
0 (Chemokine CCL2)
0 (Ddit3 protein, mouse)
0 (HSP70 Heat-Shock Proteins)
0 (Hsp70.3 protein, mouse)
0 (IL1B protein, mouse)
0 (Interleukin-1beta)
0 (NF-kappa B)
0 (Tumor Necrosis Factor-alpha)
147336-12-7 (Transcription Factor CHOP)
2V16EO95H1 (Palmitic Acid)
51110-01-1 (Somatostatin)
EC 1.14.13.39 (Nitric Oxide Synthase Type II)
EC 1.14.13.39 (Nos2 protein, mouse)
EC 2.4.2.31 (Pertussis Toxin)
EC 3.4.22.- (Casp3 protein, mouse)
EC 3.4.22.- (Casp7 protein, mouse)
EC 3.4.22.- (Caspase 3)
EC 3.4.22.- (Caspase 7)
IY9XDZ35W2 (Glucose)
Entry Date(s):: Date Created: 20190316 Date Completed: 20190319 Latest Revision: 20190319
Update Code:: 20240105
DOI:: 10.33594/000000035
PMID:: 30873823
: Czasopismo naukowe

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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 G i/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 G i/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.
Competing Interests: The authors have nothing to disclose.
(© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)

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