Effects of lipotoxicity on novel insulin secreting human pancreatic β-cell line, 1.1B4.

S Vasu, Neville McClenaghan, Janie McCluskey, Peter Flatt

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Abstract The novel insulin secreting human pancreatic β-cell line, 1.1B4, demonstrates stability in culture and many of the secretory functional attributes of human pancreatic β-cells. This study investigated the cellular responses of 1.1B4 cells to lipotoxicity. Chronic 18 h exposure of 1.1B4 cells to 0.5 mM palmitate resulted in decreased cell viability and insulin content. Secretory responses to classical insulinotropic agents and cellular Ca2+ handling were also impaired. Palmitate decreased glucokinase activity and mRNA expression of genes involved in secretory function but upregulated mRNA expression of HSPA5, EIF2A, EIF2AK3, implicating activation of ER stress response. Palmitate also induced DNA damage and apoptosis of 1.1B4 cells. These responses were accompanied by increased gene expression of antioxidant enzymes - SOD1, SOD2, CAT and GPX1. This study details molecular mechanisms underlying lipotoxicity in 1.1B4 cells and indicates the potential value of the novel beta cell line for future research.
LanguageEnglish
Pages909-918
JournalBiological Chemistry
Volume394
Issue number7
DOIs
Publication statusPublished - 6 Mar 2013

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Palmitates
Insulin-Secreting Cells
Cells
Insulin
Cell Line
Glucokinase
Messenger RNA
Gene Expression
Cell culture
Gene expression
Antioxidants
Genes
Chemical activation
Apoptosis
DNA Damage
Cell Survival
DNA
Enzymes

Cite this

Vasu, S ; McClenaghan, Neville ; McCluskey, Janie ; Flatt, Peter. / Effects of lipotoxicity on novel insulin secreting human pancreatic β-cell line, 1.1B4. In: Biological Chemistry. 2013 ; Vol. 394, No. 7. pp. 909-918.
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Effects of lipotoxicity on novel insulin secreting human pancreatic β-cell line, 1.1B4. / Vasu, S; McClenaghan, Neville; McCluskey, Janie; Flatt, Peter.

In: Biological Chemistry, Vol. 394, No. 7, 06.03.2013, p. 909-918.

Research output: Contribution to journalArticle

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AB - Abstract The novel insulin secreting human pancreatic β-cell line, 1.1B4, demonstrates stability in culture and many of the secretory functional attributes of human pancreatic β-cells. This study investigated the cellular responses of 1.1B4 cells to lipotoxicity. Chronic 18 h exposure of 1.1B4 cells to 0.5 mM palmitate resulted in decreased cell viability and insulin content. Secretory responses to classical insulinotropic agents and cellular Ca2+ handling were also impaired. Palmitate decreased glucokinase activity and mRNA expression of genes involved in secretory function but upregulated mRNA expression of HSPA5, EIF2A, EIF2AK3, implicating activation of ER stress response. Palmitate also induced DNA damage and apoptosis of 1.1B4 cells. These responses were accompanied by increased gene expression of antioxidant enzymes - SOD1, SOD2, CAT and GPX1. This study details molecular mechanisms underlying lipotoxicity in 1.1B4 cells and indicates the potential value of the novel beta cell line for future research.

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