Evidence for a sustained increase in clonal beta-cell basal intracellular Ca2+ levels after incubation in the presence of newly diagnosed type-1 diabetic patient sera. Possible role in serum-induced inhibition of insulin secretion

SJ Conroy, I Green, G Dixon, PM Byrne, J Nolan, Yasser Abdel-Wahab, Neville McClenaghan, Peter Flatt, P Newsholme

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Abstract

We have previously reported that newly diagnosed Type-1 diabetic patient sera potently suppressed insulin secretion from a clonal rat pancreatic beta-cell line (BRIN BD11) but did not alter cell viability. Here, we report that apoptosis in BRIN BD11 cells incubated in various sera types (fetal calf serum (FCS), normal human serum and Type-1 diabetic patient) was virtually undetectable. Although low levels of necrosis were detected, these were not significantly different between cells incubated in sera from different sources. ATP levels were reduced by approximately 30% while nitrite production increased twofold from BRIN BD 11 cells incubated for 24 h in the presence of Type-1 diabetic patient sera compared with normal human sera. Additionally, ATP levels were reduced by approximately 40% and DNA fragmentation increased by more than 20-fold in BRIN BD11 cells incubated in FCS in the presence of a pro-inflammatory cytokine cocktail (interleukin-1beta, tumour necrosis factor-a and interferon-gamma), compared with cells incubated in the absence of cytokines. Nitric oxide production from BRIN BD 11 cells was markedly increased (up to 10-fold) irrespective of sera type when the cytokine cocktail was included in the incubation medium. Type-1 diabetic patient sera significantly (P
LanguageEnglish
Pages53-62
JournalJournal of Endrocrinology
Volume173
Issue number1
Publication statusPublished - Apr 2002

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Insulin
Serum
Cytokines
Adenosine Triphosphate
Insulin-Secreting Cells
DNA Fragmentation
Nitrites
Interleukin-1beta
Interferon-gamma
Cell Survival
Nitric Oxide
Necrosis
Tumor Necrosis Factor-alpha
Apoptosis
Cell Line

Cite this

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title = "Evidence for a sustained increase in clonal beta-cell basal intracellular Ca2+ levels after incubation in the presence of newly diagnosed type-1 diabetic patient sera. Possible role in serum-induced inhibition of insulin secretion",
abstract = "We have previously reported that newly diagnosed Type-1 diabetic patient sera potently suppressed insulin secretion from a clonal rat pancreatic beta-cell line (BRIN BD11) but did not alter cell viability. Here, we report that apoptosis in BRIN BD11 cells incubated in various sera types (fetal calf serum (FCS), normal human serum and Type-1 diabetic patient) was virtually undetectable. Although low levels of necrosis were detected, these were not significantly different between cells incubated in sera from different sources. ATP levels were reduced by approximately 30{\%} while nitrite production increased twofold from BRIN BD 11 cells incubated for 24 h in the presence of Type-1 diabetic patient sera compared with normal human sera. Additionally, ATP levels were reduced by approximately 40{\%} and DNA fragmentation increased by more than 20-fold in BRIN BD11 cells incubated in FCS in the presence of a pro-inflammatory cytokine cocktail (interleukin-1beta, tumour necrosis factor-a and interferon-gamma), compared with cells incubated in the absence of cytokines. Nitric oxide production from BRIN BD 11 cells was markedly increased (up to 10-fold) irrespective of sera type when the cytokine cocktail was included in the incubation medium. Type-1 diabetic patient sera significantly (P",
author = "SJ Conroy and I Green and G Dixon and PM Byrne and J Nolan and Yasser Abdel-Wahab and Neville McClenaghan and Peter Flatt and P Newsholme",
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T1 - Evidence for a sustained increase in clonal beta-cell basal intracellular Ca2+ levels after incubation in the presence of newly diagnosed type-1 diabetic patient sera. Possible role in serum-induced inhibition of insulin secretion

AU - Conroy, SJ

AU - Green, I

AU - Dixon, G

AU - Byrne, PM

AU - Nolan, J

AU - Abdel-Wahab, Yasser

AU - McClenaghan, Neville

AU - Flatt, Peter

AU - Newsholme, P

PY - 2002/4

Y1 - 2002/4

N2 - We have previously reported that newly diagnosed Type-1 diabetic patient sera potently suppressed insulin secretion from a clonal rat pancreatic beta-cell line (BRIN BD11) but did not alter cell viability. Here, we report that apoptosis in BRIN BD11 cells incubated in various sera types (fetal calf serum (FCS), normal human serum and Type-1 diabetic patient) was virtually undetectable. Although low levels of necrosis were detected, these were not significantly different between cells incubated in sera from different sources. ATP levels were reduced by approximately 30% while nitrite production increased twofold from BRIN BD 11 cells incubated for 24 h in the presence of Type-1 diabetic patient sera compared with normal human sera. Additionally, ATP levels were reduced by approximately 40% and DNA fragmentation increased by more than 20-fold in BRIN BD11 cells incubated in FCS in the presence of a pro-inflammatory cytokine cocktail (interleukin-1beta, tumour necrosis factor-a and interferon-gamma), compared with cells incubated in the absence of cytokines. Nitric oxide production from BRIN BD 11 cells was markedly increased (up to 10-fold) irrespective of sera type when the cytokine cocktail was included in the incubation medium. Type-1 diabetic patient sera significantly (P

AB - We have previously reported that newly diagnosed Type-1 diabetic patient sera potently suppressed insulin secretion from a clonal rat pancreatic beta-cell line (BRIN BD11) but did not alter cell viability. Here, we report that apoptosis in BRIN BD11 cells incubated in various sera types (fetal calf serum (FCS), normal human serum and Type-1 diabetic patient) was virtually undetectable. Although low levels of necrosis were detected, these were not significantly different between cells incubated in sera from different sources. ATP levels were reduced by approximately 30% while nitrite production increased twofold from BRIN BD 11 cells incubated for 24 h in the presence of Type-1 diabetic patient sera compared with normal human sera. Additionally, ATP levels were reduced by approximately 40% and DNA fragmentation increased by more than 20-fold in BRIN BD11 cells incubated in FCS in the presence of a pro-inflammatory cytokine cocktail (interleukin-1beta, tumour necrosis factor-a and interferon-gamma), compared with cells incubated in the absence of cytokines. Nitric oxide production from BRIN BD 11 cells was markedly increased (up to 10-fold) irrespective of sera type when the cytokine cocktail was included in the incubation medium. Type-1 diabetic patient sera significantly (P

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JF - Journal of Endrocrinology

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