Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia.

S Vasu, Neville McClenaghan, Janie McCluskey, Peter Flatt

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The novel human-derived pancreatic β-cell line, 1.1B4 exhibits insulin secretion and β-cell enriched gene expression. Recent investigations of the cellular responses of this novel cell line to lipotoxicity and cytokine toxicity revealed similarities to primary human β cells. The current study has investigated the responses of 1.1B4 cells to chronic 48 and 72 h exposure to hyperglycemia to probe mechanisms of human β-cell dysfunction and cell death. Exposure to 25 mM glucose significantly reduced insulin content (p <0.05) and glucokinase activity (p <0.01) after 72 h. Basal insulin release was unaffected but acute secretory response to 16.7 mM glucose was impaired (p <0.05). Insulin release stimulated by alanine, GLP-1, KCl, elevated Ca ( 2+) and forskolin was also markedly reduced after exposure to hyperglycemia (p <0.001). In addition, PDX1 protein expression was reduced by 58% by high glucose (p <0.05). Effects of hyperglycemia on secretory function were accompanied by decreased mRNA expression of INS, GCK, PCSK1, PCSK2, PPP3CB, GJA1, ABCC8, and KCNJ11. In contrast, exposure to hyperglycemia upregulated the transcription of GPX1, an antioxidant enzyme involved in detoxification of hydrogen peroxide and HSPA4, a molecular chaperone involved in ER stress response. Hyperglycemia-induced DNA damage was demonstrated by increased % tail DNA and olive tail moment, assessed by comet assay. Hyperglycemia-induced apoptosis was evident from increased activity of caspase 3/7 and decreased BCL2 protein. These observations reveal significant changes in cellular responses and gene expression in novel human pancreatic 1.1B4 β cells exposed to hyperglycemia, illustrating the usefulness of this novel human-derived cell line for studying human β-cell biology and diabetes.
LanguageEnglish
Pages0-0
JournalISLETS
Volume5
Issue number4
Publication statusPublished - 28 Aug 2013

Fingerprint

Insulin-Secreting Cells
Hyperglycemia
Cell Line
Insulin
Glucose
Proto-Oncogene Proteins c-bcl-2
Tail
Caspase 7
Glucokinase
Gene Expression
Molecular Chaperones
Glucagon-Like Peptide 1
Comet Assay
Olea
Colforsin
Caspase 3
Alanine
Hydrogen Peroxide
DNA Damage
Cell Biology

Cite this

Vasu, S ; McClenaghan, Neville ; McCluskey, Janie ; Flatt, Peter. / Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia. In: ISLETS. 2013 ; Vol. 5, No. 4. pp. 0-0.
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abstract = "The novel human-derived pancreatic β-cell line, 1.1B4 exhibits insulin secretion and β-cell enriched gene expression. Recent investigations of the cellular responses of this novel cell line to lipotoxicity and cytokine toxicity revealed similarities to primary human β cells. The current study has investigated the responses of 1.1B4 cells to chronic 48 and 72 h exposure to hyperglycemia to probe mechanisms of human β-cell dysfunction and cell death. Exposure to 25 mM glucose significantly reduced insulin content (p <0.05) and glucokinase activity (p <0.01) after 72 h. Basal insulin release was unaffected but acute secretory response to 16.7 mM glucose was impaired (p <0.05). Insulin release stimulated by alanine, GLP-1, KCl, elevated Ca ( 2+) and forskolin was also markedly reduced after exposure to hyperglycemia (p <0.001). In addition, PDX1 protein expression was reduced by 58{\%} by high glucose (p <0.05). Effects of hyperglycemia on secretory function were accompanied by decreased mRNA expression of INS, GCK, PCSK1, PCSK2, PPP3CB, GJA1, ABCC8, and KCNJ11. In contrast, exposure to hyperglycemia upregulated the transcription of GPX1, an antioxidant enzyme involved in detoxification of hydrogen peroxide and HSPA4, a molecular chaperone involved in ER stress response. Hyperglycemia-induced DNA damage was demonstrated by increased {\%} tail DNA and olive tail moment, assessed by comet assay. Hyperglycemia-induced apoptosis was evident from increased activity of caspase 3/7 and decreased BCL2 protein. These observations reveal significant changes in cellular responses and gene expression in novel human pancreatic 1.1B4 β cells exposed to hyperglycemia, illustrating the usefulness of this novel human-derived cell line for studying human β-cell biology and diabetes.",
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Vasu, S, McClenaghan, N, McCluskey, J & Flatt, P 2013, 'Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia.', ISLETS, vol. 5, no. 4, pp. 0-0.

Cellular responses of novel human pancreatic β-cell line, 1.1B4 to hyperglycemia. / Vasu, S; McClenaghan, Neville; McCluskey, Janie; Flatt, Peter.

In: ISLETS, Vol. 5, No. 4, 28.08.2013, p. 0-0.

Research output: Contribution to journalArticle

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AB - The novel human-derived pancreatic β-cell line, 1.1B4 exhibits insulin secretion and β-cell enriched gene expression. Recent investigations of the cellular responses of this novel cell line to lipotoxicity and cytokine toxicity revealed similarities to primary human β cells. The current study has investigated the responses of 1.1B4 cells to chronic 48 and 72 h exposure to hyperglycemia to probe mechanisms of human β-cell dysfunction and cell death. Exposure to 25 mM glucose significantly reduced insulin content (p <0.05) and glucokinase activity (p <0.01) after 72 h. Basal insulin release was unaffected but acute secretory response to 16.7 mM glucose was impaired (p <0.05). Insulin release stimulated by alanine, GLP-1, KCl, elevated Ca ( 2+) and forskolin was also markedly reduced after exposure to hyperglycemia (p <0.001). In addition, PDX1 protein expression was reduced by 58% by high glucose (p <0.05). Effects of hyperglycemia on secretory function were accompanied by decreased mRNA expression of INS, GCK, PCSK1, PCSK2, PPP3CB, GJA1, ABCC8, and KCNJ11. In contrast, exposure to hyperglycemia upregulated the transcription of GPX1, an antioxidant enzyme involved in detoxification of hydrogen peroxide and HSPA4, a molecular chaperone involved in ER stress response. Hyperglycemia-induced DNA damage was demonstrated by increased % tail DNA and olive tail moment, assessed by comet assay. Hyperglycemia-induced apoptosis was evident from increased activity of caspase 3/7 and decreased BCL2 protein. These observations reveal significant changes in cellular responses and gene expression in novel human pancreatic 1.1B4 β cells exposed to hyperglycemia, illustrating the usefulness of this novel human-derived cell line for studying human β-cell biology and diabetes.

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