scholarly journals Kallikrein in rat pancreatic tissue after beta cell destruction or acinar cell atrophy.

1981 ◽  
Vol 29 (12) ◽  
pp. 1431-1436 ◽  
Author(s):  
T B Orstavik ◽  
I B Brekke ◽  
J Alumets ◽  
O A Carretero
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Acinar Cell ◽  
Pancreatic Beta Cells ◽  
Exocrine Pancreas ◽  
Acinar Cells ◽  
Beta Cell Destruction ◽  
Cell Destruction ◽  
Duct Occlusion ◽  
Cell Atrophy

The purpose of this study was to determine whether glandular kallikrein in rat pancreas is located in the beta cells of the endocrine pancreas or in the acinar cells of the exocrine pancreas. Kallikrein was measured by radial immunodiffusion and a direct radioimmunoassay in homogenates of pancreas obtained from 1) control rats, 2) rats with pancreatic beta cells selectively destroyed by streptozotocin, and 3) rats with acinar cell atrophy induced by pancreatic duct occlusion. Beta cell destruction was confirmed by the presence of hyperglycemia and by an almost total depletion of insulin-producing cells as demonstrated immunohistochemically. Acinar cell atrophy was confirmed histologically and by an almost total depletion of trypsin-like enzymes in pancreatic homogenates. The concentration of kallikrein in pancreatic homogenates was unchanged after beta cell destruction, whereas it was greatly decreased following acinar cell atrophy. Kallikrein was, by immunohistochemistry, demonstrated in the acinar cell only. The immunohistochemical localization of kallikrein agrees with the above results. These studies strongly indicate that kallikrein is predominantly located in the acinar cells of the exocrine pancreas.

scholarly journals The absence of H-2 antigens from mouse pancreatic beta-cells demonstrated by immunoferritin labeling.

1979 ◽  
Vol 150 (1) ◽  
pp. 1-9 ◽  
Author(s):  
E L Parr
Keyword(s):  
Endothelial Cells ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Beta Cell ◽  
Pancreatic Duct ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Acinar Cells ◽  
Cell Types ◽  
Capillary Endothelial Cells

Islets of Langerhans were isolated from mouse pancreases and fixed in periodatelysine-paraformaldehyde. The fixed islets were then dissociated with trypsin and EDTA to yield cell suspensions that contained mainly four cell types; beta-cells, capillary endothelial cells, acinar cells, and pancreatic duct epithelial cells. The nonislet cells were probably associated wtih the surface of the isolated islets. The H-2 antigens of the dissociated pancreatic cells were labeled with an immunoferritin technique. Pancreatic duct epithelial cells showed specific ferritin labeling on their lateral cell membranes but not on apical microvillus membranes. Acinar cells were also labeled on lateral membranes, and the capillary endothelial cells were labeled on both the luminal and albuminal aspects of their surface membranes. In contrast, pancreatic beta-cells were unlabeled. The number of ferritin molecules per unit length of beta-cell membrane was essentially the same on cells from the antigenic strain and the congeneic control strain, and was about 200-fold less than on the labeled pancreatic duct epithelial cell lateral membranes. Pancreatic beta-cells are therefore one of six known epithelial cell types on which H-2 antigens can not be detected by immunoferritin labeling. The apparent absence of H-2 antigens from these cells suggests a study of the viability of beta-cells in allografts of dissociated islet cells, in which the beta-cell would not be in contact with antigenic cells. Such studies might lead to a new approach to the control of diabetes mellitus by transplantation.

scholarly journals The microRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts

2021 ◽  
Author(s):  
Geert Antoine Martens ◽  
Geert Stange ◽  
Lorenzo Piemonti ◽  
Jasper Anckaert ◽  
Zhidong Ling ◽  
...  
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Beta Cells ◽  
Islet Transplantation ◽  
Beta Cell Death ◽  
Beta Cell Destruction ◽  
Cell Destruction ◽  
Graft Outcome ◽  
Plasma Microrna

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. MicroRNA-375 (miR-375) ranks among top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 hour before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to identification of 8 microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients, by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

scholarly journals Liraglutide and sitagliptin counter beta- to alpha-cell transdifferentiation in diabetes

2020 ◽  
Vol 245 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Neil Tanday ◽  
Peter R Flatt ◽  
Nigel Irwin ◽  
R Charlotte Moffett
Keyword(s):  
Insulin Resistance ◽  
Beta Cell ◽  
Beta Cells ◽  
Lineage Tracing ◽  
Alpha Cell ◽  
Beta Cell Destruction ◽  
Glucose Levels ◽  
Cell Destruction ◽  
Cell Transdifferentiation ◽  
The Impact

Transdifferentiation of beta- to alpha-cells has been implicated in the pathogenesis of diabetes. To investigate the impact of contrasting aetiologies of beta-cell stress, as well as clinically approved incretin therapies on this process, lineage tracing of beta-cells in transgenic Ins1 Cre/+/Rosa26-eYFP mice was investigated. Diabetes-like syndromes were induced by streptozotocin (STZ), high fat feeding (HFF) or hydrocortisone (HC), and effects of treatment with liraglutide or sitagliptin were investigated. Mice developed the characteristic metabolic features associated with beta-cell destruction or development of insulin resistance. Liraglutide was effective in preventing weight gain in HFF mice, with both treatments decreasing energy intake in STZ and HC mice. Treatment intervention also significantly reduced blood glucose levels in STZ and HC mice, as well as increasing either plasma or pancreatic insulin while decreasing circulating or pancreatic glucagon in all models. The recognised changes in pancreatic morphology induced by STZ, HFF or HC were partially, or fully, reversed by liraglutide and sitagliptin, and related to advantageous effects on alpha- and beta-cell growth and survival. More interestingly, induction of diabetes-like phenotype, regardless of pathogenesis, led to increased numbers of beta-cells losing their identity, as well as decreased expression of Pdx1 within beta-cells. Both treatment interventions, and especially liraglutide, countered detrimental islet cell transitioning effects in STZ and HFF mice. Only liraglutide imparted benefits on beta- to alpha-cell transdifferentiation in HC mice. These data demonstrate that beta- to alpha-cell transdifferentiation is a common consequence of beta-cell destruction or insulin resistance and that clinically approved incretin-based drugs effectively limit this.

scholarly journals Mediators and mechanisms of pancreatic beta-cell death in type 1 diabetes

2008 ◽  
Vol 52 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Pierre Pirot ◽  
Alessandra K. Cardozo ◽  
Décio L. Eizirik
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Map Kinases ◽  
Pancreatic Beta Cell ◽  
Insulin Deficiency ◽  
Beta Cell Destruction ◽  
Pro Inflammatory Cytokines

Type 1 diabetes mellitus (T1D) is characterized by severe insulin deficiency resulting from chronic and progressive destruction of pancreatic beta-cells by the immune system. The triggering of autoimmunity against the beta-cells is probably caused by environmental agent(s) acting in the context of a predisposing genetic background. Once activated, the immune cells invade the islets and mediate their deleterious effects on beta-cells via mechanisms such as Fas/FasL, perforin/granzyme, reactive oxygen and nitrogen species and pro-inflammatory cytokines. Binding of cytokines to their receptors on the beta-cells activates MAP-kinases and the transcription factors STAT-1 and NFkappa-B, provoking functional impairment, endoplasmic reticulum stress and ultimately apoptosis. This review discusses the potential mediators and mechanisms leading to beta-cell destruction in T1D.

Beta-cell destruction in NOD mice correlates with Fas (CD95) expression on beta-cells and proinflammatory cytokine expression in islets

Diabetes ◽  
1999 ◽  
Vol 48 (1) ◽  
pp. 21-28 ◽  
Author(s):  
W. Suarez-Pinzon ◽  
O. Sorensen ◽  
R. C. Bleackley ◽  
J. F. Elliott ◽  
R. V. Rajotte ◽  
...  
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Proinflammatory Cytokine ◽  
Nod Mice ◽  
Cytokine Expression ◽  
Beta Cell Destruction ◽  
Cell Destruction ◽  
Proinflammatory Cytokine Expression

scholarly journals Monoclonal antibody-mediated cytotoxicity against rat Beta cells detected in vitro does not cause Beta-cell destruction in vivo

Diabetologia ◽  
1992 ◽  
Vol 35 (7) ◽  
pp. 608-613 ◽  
Author(s):  
B. Ziegler ◽  
S. Lucke ◽  
E. K�hler ◽  
B. Hehmke ◽  
M. Schlosser ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Destruction ◽  
Cell Destruction

scholarly journals The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1693
Author(s):  
Geert A. Martens ◽  
Geert Stangé ◽  
Lorenzo Piemonti ◽  
Jasper Anckaert ◽  
Zhidong Ling ◽  
...  
Keyword(s):  
Cell Death ◽  
Beta Cell ◽  
Beta Cells ◽  
Islet Transplantation ◽  
Beta Cell Death ◽  
Beta Cell Destruction ◽  
Cell Destruction ◽  
Graft Outcome ◽  
Plasma Microrna

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. microRNA-375 (miR-375) ranks among the top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 h before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to the identification of eight microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome, and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

scholarly journals Endoplasmic Reticulum-Mitochondria Crosstalk and Beta-Cell Destruction in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Saurabh Vig ◽  
Joost M. Lambooij ◽  
Arnaud Zaldumbide ◽  
Bruno Guigas
Keyword(s):  
Endoplasmic Reticulum ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Destruction ◽  
Unfolded Protein ◽  
Cell Destruction ◽  
The Unfolded Protein Response ◽  
And Function

Beta-cell destruction in type 1 diabetes (T1D) results from the combined effect of inflammation and recurrent autoimmunity. In response to inflammatory signals, beta-cells engage adaptive mechanisms where the endoplasmic reticulum (ER) and mitochondria act in concert to restore cellular homeostasis. In the recent years it has become clear that this adaptive phase may trigger the development of autoimmunity by the generation of autoantigens recognized by autoreactive CD8 T cells. The participation of the ER stress and the unfolded protein response to the increased visibility of beta-cells to the immune system has been largely described. However, the role of the other cellular organelles, and in particular the mitochondria that are central mediator for beta-cell survival and function, remains poorly investigated. In this review we will dissect the crosstalk between the ER and mitochondria in the context of T1D, highlighting the key role played by this interaction in beta-cell dysfunctions and immune activation, especially through regulation of calcium homeostasis, oxidative stress and generation of mitochondrial-derived factors.

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