scholarly journals Beneficial effect of 1,25 dihydroxyvitamin D3 on cytokine-treated human pancreatic islets

2001 ◽  
Vol 169 (1) ◽  
pp. 161-168 ◽  
Author(s):  
R Riachy ◽  
B Vandewalle ◽  
S Belaich ◽  
J Kerr-Conte ◽  
V Gmyr ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Cell Viability ◽  
Pancreatic Islets ◽  
Mhc Class I ◽  
Class I ◽  
Insulin Content ◽  
Hsp70 Expression ◽  
Human Pancreatic Islets ◽  
Mnsod Activity

We examined whether 1,25 dihydroxyvitamin D(3) (1,25 D(3)), the active form of vitamin D involved in the regulation of the immune system, may also protect human pancreatic islet cells from destruction induced by cytokines. In this study, we specifically investigated the effect of 1,25 D(3) on oxidative stress and major histocompatibility complex (MHC) induction, both implicated in cytokine-induced islet cell dysfunction and destruction. We also investigated the effects of 1,25 D(3) on interleukin (IL)-6, a pleiotropic cytokine implicated in the pathogenesis of immunoinflammatory disorders. Human pancreatic islets, isolated from heart-beating donors, were treated with a combination of three cytokines, IL-1beta+tumor necrosis factor alpha+interferon gamma, in the presence or absence of vitamin D, and compared with with untreated control cells. Metabolic activity was assessed by cell viability and insulin content. Oxidative stress was estimated by heat shock protein 70 (hsp70) expression, cell manganese superoxide dismutase (MnSOD) activity and nitrite release, a reflexion of nitric oxide (NO) synthesis. Variation of immunogenicity of islet preparations was determined by analysis of the MHC class I and class II transcripts. Inflammatory status was evaluated by IL-6 production. After 48 h of contact with cytokines, insulin content was significantly decreased by 40% but cell viability was not altered. MHC expression significantly increased six- to sevenfold as well as NO and IL-6 release (two- to threefold enhancement). MnSOD activity was not significantly induced and hsp70 expression was not affected by the combination of cytokines. The addition of 1,25 D(3) significantly reduced nitrite release, IL-6 production and MHC class I expression which then became not significantly different from controls. These results suggest that the effect of 1,25 D(3) in human pancreatic islets cells may be a reduction of the vulnerability of cells to cytotoxic T lymphocytes and a reduction of cytotoxic challenge. Hence, 1,25 D(3) might play a role in the prevention of type 1 diabetes and islet allograft rejection.

scholarly journals A subgroup of lupus patients with nephritis, innate T cell activation and low vitamin D is identified by the enhancement of circulating MHC class I‐related chain A

2019 ◽  
Vol 196 (3) ◽  
pp. 336-344
Author(s):  
M. Pérez‐Ferro ◽  
F. I. Romero‐Bueno ◽  
C. Serrano del Castillo ◽  
I. Mahillo ◽  
A. Alvear ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cell ◽  
Mhc Class I ◽  
T Cell Activation ◽  
Cell Activation ◽  
Class I

scholarly journals Essential Role of Thioredoxin 2 in Mitigating Oxidative Stress in Retinal Epithelial Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Eriko Sugano ◽  
Namie Murayama ◽  
Maki Takahashi ◽  
Kitako Tabata ◽  
Makoto Tamai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Viability ◽  
Metabolic Activity ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Hsp70 Expression ◽  
Age Related ◽  
Shock Proteins ◽  
Thioredoxin 2

The retina is constantly subjected to oxidative stress, which is countered by potent antioxidative systems present in retinal pigment epithelial (RPE) cells. Disruption of these systems leads to the development of age-related macular degeneration. Thioredoxin 2 (Trx2) is a potent antioxidant, which acts directly on mitochondria. In the present study, oxidative stress was induced in the human RPE cell line (ARPE-19) using 4-hydroxynonenal (4-HNE) or C2-ceramide. The protective effect of Trx2 against oxidative stress was investigated by assessing cell viability, the kinetics of cell death, mitochondrial metabolic activity, and expression of heat shock proteins (Hsps) in Trx2-overexpressing cell lines generated by transfecting ARPE cells with an adeno-associated virus vector encoding Trx2. We show that overexpression of Trx2 reduced cell death induced by both agents when they were present in low concentrations. Moreover, early after the induction of oxidative stress Trx2 played a key role in the maintenance of the cell viability through upregulation of mitochondrial metabolic activity and inhibition of Hsp70 expression.

IDDM in BB rats. Enhanced MHC class I heavy-chain gene expression in pancreatic islets

Diabetes ◽  
1988 ◽  
Vol 37 (10) ◽  
pp. 1411-1418 ◽  
Author(s):  
S. J. Ono ◽  
B. Issa-Chergui ◽  
E. Colle ◽  
R. D. Guttmann ◽  
T. A. Seemayer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islets ◽  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Bb Rats

scholarly journals Author Correction: Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Francesca Urbano ◽  
Marco Bugliani ◽  
Agnese Filippello ◽  
Alessandra Scamporrino ◽  
Stefania Di Mauro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Islets ◽  
Direct Effect ◽  
Mitochondrial Function ◽  
Β Cells ◽  
Human Pancreatic Islets

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

scholarly journals Ex vivo transcriptional profiling of human pancreatic islets following chronic exposure to monounsaturated fatty acids

2007 ◽  
Vol 196 (3) ◽  
pp. 455-464 ◽  
Author(s):  
George Bikopoulos ◽  
Aurelio da Silva Pimenta ◽  
Simon C Lee ◽  
Jonathan R Lakey ◽  
Sandy D Der ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Pancreatic Islets ◽  
Chronic Exposure ◽  
Ex Vivo ◽  
Transcriptional Profiling ◽  
Gene Clusters ◽  
Human Islets ◽  
Insulin Content ◽  
Ros Generation ◽  
Human Pancreatic Islets

The aim of this study was to assess the effects of chronic free fatty acid (FFA) exposure on gene expression and the functional state of human pancreatic islets. Chronic exposure of islets to oleate (OA) resulted in a significant reduction in glucose-stimulated insulin secretion (GSIS) compared with control (466±82 vs 234±57 ng/μg DNA, P<0.05). OA treatment also led to reduction in total insulin content of the islets (17 609±3816 vs 10 599±3876 ng insulin/μg DNA) and to an increase in the rate of reactive oxygen species (ROS) generation. Interestingly, the suppressive effects of OA on biosynthesis and secretion of insulin were accompanied by alteration in the expression of 40 genes, as determined by microarray analysis and subsequent qPCR validation. The majority of genes regulated by OA encoded metabolic enzymes. The expression of enzymes involved in oxidative defense was elevated, indicating a link between ROS generation and antioxidant defense activation. Additionally, pretreatment of human islets with OA led to a significant increase (30%) in the rate of oxidation of this fatty acid and to a significant decrease (75%) in glucose oxidation. Importantly, individual analysis of gene clusters from the islets of all donors revealed the induction of genes involved in inflammation and immunity, which provides further evidence that FFA are risk factors for the development of type 2 diabetes. In summary, our data indicate that chronic exposure of human islets to FFA activates inflammatory and metabolic pathways that lead to oxidative stress, reduced β-cell insulin content, and inhibition of GSIS.

scholarly journals Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Francesca Urbano ◽  
Marco Bugliani ◽  
Agnese Filippello ◽  
Alessandra Scamporrino ◽  
Stefania Di Mauro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pancreatic Islets ◽  
Cell Function ◽  
Antioxidant Defense System ◽  
Design Strategies ◽  
Β Cell ◽  
Mitochondrial Oxidative Stress ◽  
Human Pancreatic Islets ◽  
Increased Risk ◽  
Β Cell Function

AbstractStatins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins.

IDDM in BB Rats: Enhanced MHC Class I Heavy-Chain Gene Expression in Pancreatic Islets

Diabetes ◽  
1988 ◽  
Vol 37 (10) ◽  
pp. 1411-1418 ◽  
Author(s):  
S. Jeremy Ono ◽  
B. Issa-Chergui ◽  
E. Colle ◽  
R. D. Guttmann ◽  
T. A. Seemayer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pancreatic Islets ◽  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Bb Rats

scholarly journals The direct effects of the angiotensin-converting enzyme inhibitors, zofenoprilat and enalaprilat, on isolated human pancreatic islets

2006 ◽  
Vol 154 (2) ◽  
pp. 355-361 ◽  
Author(s):  
Roberto Lupi ◽  
Silvia Del Guerra ◽  
Marco Bugliani ◽  
Ugo Boggi ◽  
Franco Mosca ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Ace Inhibitors ◽  
High Glucose ◽  
Ace Inhibitor ◽  
Human Islets ◽  
Converting Enzyme ◽  
Β Cells ◽  
Human Pancreatic Islets

Objective: Data from prospective studies suggest a significant reduction in the risk of new diabetes from drug therapies containing angiotensin-converting enzyme (ACE) inhibitors. Since the renin–angiotensin system (RAS) has been found locally in several tissues and cells, including pancreatic islets, we hypothesized that the positive metabolic effects of ACE inhibitors may be due to a beneficial action of these compounds on insulin-secreting β-cells. Design and methods: Isolated human pancreatic islets were studied after 24 h of incubation with 22.2 mmol/l glucose, with or without the presence in the incubation medium of 0.5–6.0 mmol/l zofenoprilat or enalaprilat, ACE inhibitor drugs which differ by the presence of a sulphydryl or a carboxyl group in their structural formula. Functional and molecular studies were then performed to assess insulin secretion, redox balance, mRNA and protein expression. Results: Angiotensinogen, ACE and angiotensin type 1 receptor mRNA expression increased in islets cultured in high glucose; this was similarly prevented by the presence of either ACE inhibitor. As expected, preculture of human islets in high glucose determined a marked reduction in insulin secretion which was associated with enhanced oxidative stress, as shown by increased nitrotyrosine concentrations, and enhanced expression of protein kinase C β and NADPH oxidase. The presence of either of the ACE inhibitors counteracted several of the deleterious effects of high glucose exposure, including reduction of insulin secretion and increased oxidative stress; zofenoprilat showed significantly more marked effects. Conclusions: These results showed that: (a) RAS molecules are present in human islets and their expression is sensitive to glucose concentration, (b) ACE inhibitors, and in particular zofenoprilat, protect human islets from glucotoxicity and (c) the effects of ACE inhibition are associated with decreased oxidative stress. Together, these findings provide evidence that the possible beneficial effects of ACE inhibitors in human diabetes are due, at least in part, to a protective action on pancreatic β-cells.

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