The mechanism of nitric oxide-induced apoptosis in the pancreatic β-cell may involve cGMP and protein kinase G

2018 ◽  
pp. 115-124
Author(s):  
Anne C. Loweth ◽  
Gwyn T. Williams ◽  
Roger D. Hurst ◽  
John H.B. Scarpello ◽  
Noel G. Morgan
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
Protein Kinase G ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Induced Apoptosis

Evidence for the involvement of cGMP and protein kinase G in nitric oxide-induced apoptosis in the pancreatic B-cell line, HIT-T15

FEBS Letters ◽  
1997 ◽  
Vol 400 (3) ◽  
pp. 285-288 ◽  
Author(s):  
Anne C Loweth ◽  
Gwyn T Williams ◽  
John H.B Scarpello ◽  
Noel G Morgan
Keyword(s):  
Nitric Oxide ◽  
Protein Kinase ◽  
B Cell ◽  
Cell Line ◽  
Protein Kinase G ◽  
Pancreatic B Cell ◽  
Induced Apoptosis

scholarly journals Protein Kinase B/Akt Prevents Fatty Acid-induced Apoptosis in Pancreatic β-Cells (INS-1)

2002 ◽  
Vol 277 (51) ◽  
pp. 49676-49684 ◽  
Author(s):  
Christian E. Wrede ◽  
Lorna M. Dickson ◽  
Melissa K. Lingohr ◽  
Isabelle Briaud ◽  
Christopher J. Rhodes
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Cell Apoptosis ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Glycogen Synthase Kinase ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Induced Apoptosis

Free fatty acids (FFA) have been reported to reduce pancreatic β-cell mitogenesis and to increase apoptosis. Here we show that the FFA, oleic acid, increased apoptosis 16-fold in the pancreatic β-cell line, INS-1, over a 18-h period as assessed by Hoechst 33342/propidium iodide staining and caspase-3 and -9 activation, with negligible necrosis. A parallel analysis of the phosphorylation activation of protein kinase B (PKB) showed this was reduced in the presence of FFA that correlated with the incidence of apoptosis. At stimulatory 15 mmglucose and/or in the added presence of insulin-like growth factor 1, FFA-induced β-cell apoptosis was lessened compared with that at a basal 5 mmglucose. However, most strikingly, adenoviral mediated expression of a constitutively active PKB, but not a “kinase-dead” PKB variant, essentially prevented FFA-induced β-cell apoptosis under all glucose/insulin-like growth factor 1 conditions. Further analysis of pro-apoptotic downstream targets of PKB, implicated a role for PKB-mediated phosphorylation inhibition of glycogen synthase kinase-3α/β and the forkhead transcription factor, FoxO1, in protection of FFA-induced β-cell apoptosis. In addition, down-regulation of the pro-apoptotic tumor suppresser protein, p53, via PKB-mediated phosphorylation of MDM2 might also play a role in partially protecting β-cells from FFA-induced apoptosis. Adenoviral mediated expression of wild type p53 potentiated FFA-induced β-cell apoptosis, whereas expression of a dominant negative p53 partly inhibited β-cell apoptosis by ∼50%. Hence, these data demonstrate that PKB activation plays an important role in promoting pancreatic β-cell survival in part via inhibition of the pro-apoptotic proteins glycogen synthase kinase-3α/β, FoxO1, and p53. This, in turn, provides novel insight into the mechanisms involved in FFA-induced β-cell apoptosis.

cGMP-independent anti-apoptotic effect of nitric oxide on thapsigargin-induced apoptosis in the pancreatic β-cell line INS-1

Life Sciences ◽  
2008 ◽  
Vol 83 (25-26) ◽  
pp. 865-870 ◽  
Author(s):  
Akiko Noguchi ◽  
Masahiro Takada ◽  
Koichi Nakayama ◽  
Tomohisa Ishikawa
Keyword(s):  
Nitric Oxide ◽  
Cell Line ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Apoptotic Effect ◽  
Induced Apoptosis

scholarly journals Physiological concentrations of interleukin-6 directly promote insulin secretion, signal transduction, nitric oxide release, and redox status in a clonal pancreatic β-cell line and mouse islets

2012 ◽  
Vol 214 (3) ◽  
pp. 301-311 ◽  
Author(s):  
Mauricio da Silva Krause ◽  
Aline Bittencourt ◽  
Paulo Ivo Homem de Bittencourt ◽  
Neville H McClenaghan ◽  
Peter R Flatt ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Cell Metabolism ◽  
Redox Status ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Upstream Kinase ◽  
Mouse Islets

Interleukin-6 (IL6) has recently been reported to promote insulin secretion in a glucagon-like peptide-1-dependent manner. Herein, the direct effects of IL6 (at various concentrations from 0 to 1000 pg/ml) on pancreatic β-cell metabolism, AMP-activated protein kinase (AMPK) signaling, insulin secretion, nitrite release, and redox status in a rat clonal β-cell line and mouse islets are reported. Chronic insulin secretion (in μg/mg protein per 24 h) was increased from 128.7±7.3 (no IL6) to 178.4±7.7 (at 100 pg/ml IL6) in clonal β-cells and increased significantly in islets incubated in the presence of 5.5 mM glucose for 2 h, from 0.148 to 0.167±0.003 ng/islet. Pretreatment with IL6 also induced a twofold increase in basal and nutrient-stimulated insulin secretion in subsequent 20 min static incubations. IL6 enhanced both glutathione (GSH) and glutathione disulphide (GSSG) by nearly 20% without changing intracellular redox status (GSSG/GSH). IL6 dramatically increased iNOS expression (byca. 100-fold) with an accompanying tenfold rise in nitrite release in clonal β-cells. Phosphorylated AMPK levels were elevated approximately twofold in clonal β-cells and mouse islet cells. Calmodulin-dependent protein kinase kinase levels (CaMKK), an upstream kinase activator of AMPK, were also increased by 50% after IL6 exposure (in β-cells and islets). Our data have demonstrated that IL6 can stimulate β-cell-dependent insulin secretion via direct cell-based mechanisms. AMPK, CaMKK (an upstream kinase activator of AMPK), and the synthesis of nitric oxide appear to alter cell metabolism to benefit insulin secretion. In summary, IL6 exerts positive effects on β-cell signaling, metabolism, antioxidant status, and insulin secretion.

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