scholarly journals Pancreatic Tissue Proteomics Unveils Key Proteins, Pathways, and Networks Associated with Type 1 Diabetes

2020 ◽  
Vol 14 (6) ◽  
pp. 2000053
Author(s):  
Jongmin Woo ◽  
Putty‐Reddy Sudhir ◽  
Qibin Zhang
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Tissue ◽  
Tissue Proteomics

scholarly journals One in Ten CD8+ Cells in the Pancreas of Living Individuals With Recent Onset Type 1 Diabetes Recognizes the Preproinsulin Epitope PPI15-24

2021 ◽  
Author(s):  
Ada Admin ◽  
Teresa Rodriguez-Calvo ◽  
Lars Krogvold ◽  
Natalie Amirian ◽  
Knut Dahl-Jørgensen ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cd8 T Cells ◽  
Pancreatic Tissue ◽  
Cell Reactivity ◽  
Tissue Samples ◽  
Recent Onset ◽  
Onset Type

In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with short and long disease duration. The Diabetes Virus Detection (DiViD) study collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset type 1 diabetes. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8+ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We additionally show the heterogeneity of islet distribution and CD8+ T cell infiltration. Our findings contribute to the current limited existing knowledge on T cell reactivity in the pancreas of recent onset type 1 diabetic donors, and indicate that antigen-specific therapies directed towards preproinsulin could have high clinical impact.

REACTIVATION OF TYPE 1 DIABETES IN PATIENTS RECEIVING HUMAN FETAL PANCREATIC TISSUE TRANSPLANTS WITHOUT IMMUNOSUPPRESSION 1

2000 ◽  
Vol 69 (1) ◽  
pp. 166 ◽  
Author(s):  
Barbara M. Brooks-Worrell ◽  
Karen P. Peterson ◽  
Charles M. Peterson ◽  
Jerry P. Palmer ◽  
Lois Jovanovic
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Tissue ◽  
Tissue Transplants

scholarly journals Wip1 regulates the immunomodulatory effects of murine mesenchymal stem cells in type 1 diabetes mellitus via targeting IFN-α/BST2

2020 ◽  
Author(s):  
Na Zhou ◽  
Weijiang Liu ◽  
Yuanlin Liu ◽  
Xue Li ◽  
Yang Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Type 1 Diabetes ◽  
Mesenchymal Stem Cells ◽  
Type 1 Diabetes Mellitus ◽  
Pancreatic Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Effects ◽  
Wild Type

Abstract Background: Mesenchymal stem cells (MSCs) shows significant therapeutic effects in type 1 diabetes mellitus (T1DM) as they could regulate the inflammatory processes. However, little is known about the process of MSCs immunosuppression in T1DM. In this study, we investigated the effects of wild type p53-induce phosphatase 1 (Wip1) on regulating MSCs immunosuppressive capacities in T1DM mice.Methods: Primary wild type (Wip1+/+) MSCs and Wip1 knockout (Wip1−/−) MSCs were cultured in vitro. T1DM mouse model was induced with streptozotocin and then was treated with Wip1+/+ MSCs (5 × 105) or Wip1−/− MSCs (5 × 105) by tail vein injection. The general physiological states of T1DM mice were measured every week. Moreover, the pathological changes in the pancreatic tissue were observed. Enzyme-linked immunosorbent assay (ELISA) and flow cytometry were used to detect the expressions of inflammatory cytokines in mice.Results: Wip1 −/− MSCs had lower therapeutic effects in T1DM mice. Moreover, we screened and confirmed bone marrow stromal cell antigen2 (BST2) gene that showed the target gene for Wip1 through gene chips, quantitative polymerase chain reaction and Western blot. Wip1−/− MSCs exhibited lower immunosuppressive capacity, as evidenced by enhanced expression of BST2, with concurrent increased expression of interferon-α (IFN-α). In vivo distribution analysis results indicated that Wip1−/− MSCs homed to the damaged pancreatic tissue. Wip1−/− MSCs influenced the expression of immune factors by remarkably increasing the expression of tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A), IFN-α, IFN-β, and IFN-γ and decreasing the expression of IL-4 and IL-10.Conclusions: Wip1 affects MSCs immunomodulation by regulating the expression of IFN-α/BST2. These findings suggest that Wip1 is required to regulate the therapeutic effects of MSCs on T1DM treatment, indicating a novel role of Wip1 in immunoregulation.

scholarly journals Integrated analysis of the pancreas and islets reveals unexpected findings in human male with type 1 diabetes

2021 ◽  
Author(s):  
Rachana Haliyur ◽  
John T Walker ◽  
May Sanyoura ◽  
Conrad V Reihsmann ◽  
Shristi Shrestha ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Genetic Risk Score ◽  
Cell Mass ◽  
Pancreatic Tissue ◽  
Isolated Islets ◽  
Histological Evaluation ◽  
Integrated Analysis ◽  
Β Cells ◽  
Β Cell

Abstract Clinical and pathologic heterogeneity in type 1 diabetes is increasingly being recognized. Findings in the islets and pancreas of a 22-year-old male with 8 years of type 1 diabetes were discordant with expected results and clinical history (islet autoantibodies negative, A1C 11.9%) and led to comprehensive investigation to define the functional, molecular, genetic, and architectural features of the islets and pancreas in order to understand the cause of the donor’s diabetes. Examination of the donor’s pancreatic tissue found substantial, but reduced, β cell mass with some islets devoid of β cells (29.3% of 311 islets) while other islets had many β cells. Surprisingly, isolated islets from the donor pancreas had substantial insulin secretion that is uncommon for type 1 diabetes of this duration. Targeted and whole genome sequencing and analysis did not uncover monogenic causes of diabetes but did identify high-risk HLA haplotypes and a genetic risk score suggestive of type 1 diabetes. Further review of pancreatic tissue found islet inflammation and some previously described α cell molecular features seen in type 1 diabetes. By integrating analysis of isolated islets, histological evaluation of the pancreas, and genetic information, we concluded that the donor’s clinical insulin deficiency was most likely the result autoimmune-mediated β cell loss, but that the constellation of findings was not typical for type 1 diabetes. This report highlights the pathologic and functional heterogeneity that can be present in type 1 diabetes.

Islet of Langerhans Transplantation for the Treatment of Type 1 Diabetes

Swiss Surgery ◽  
2003 ◽  
Vol 9 (5) ◽  
pp. 242-246 ◽  
Author(s):  
Bucher ◽  
Mathe ◽  
Bosco ◽  
Andres ◽  
Bühler ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Enzymatic Digestion ◽  
Pancreatic Tissue ◽  
Islet Of Langerhans ◽  
Insulin Independence ◽  
Islet Mass ◽  
Clinical Islet Transplantation ◽  
Islet Transplants

Islet of Langerhans transplantation is gaining recognition as a therapy for type 1 diabetes. The procedure involves enzymatic digestion of the pancreatic tissue, purification of the islets from the exocrine tissue, infusion of the islets into the portal vein and implantation in the liver. Until 1999, an overall rate of insulin independence of 14% at one year was reported in the International Islet Transplant Registry. The results of the "Edmonton protocol" since 2000 were a breakthrough in the field, with reports of 80% insulin independence at 1-year after solitary islet transplantation in non uremic patients with brittle type 1 diabetes. A rapamycin-based, steroid-free, islet-sparing immunosuppressive regimen was designed and the problem of the insufficient islet mass was tackled by sequential infusions of islets isolated from at least two pancreata. The University of Geneva has been involved in clinical islet transplantation since 1992, and has performed 51 allogeneic and 17 autologous. Twenty-one patients have been transplanted in Geneva since 2002. They were five solitary islet transplants, 14 islet after kidney transplants and two simultaneous islet-kidney (SIK) recipients. Insulin independence was achieved in 67%.

scholarly journals Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study

Diabetologia ◽  
2021 ◽  
Author(s):  
Sami Oikarinen ◽  
Lars Krogvold ◽  
Bjørn Edwin ◽  
Trond Buanes ◽  
Olle Korsgren ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Pancreatic Islets ◽  
Culture Medium ◽  
Mononuclear Cells ◽  
Virus Detection ◽  
Duodenal Mucosa ◽  
Pancreatic Tissue ◽  
Newly Diagnosed ◽  
Peripheral Blood Mononuclear

Abstract Aims/hypothesis The Diabetes Virus Detection (DiViD) study is the first study to laparoscopically collect pancreatic tissue and purified pancreatic islets together with duodenal mucosa, serum, peripheral blood mononuclear cells (PBMCs) and stools from six live adult patients (age 24–35 years) with newly diagnosed type 1 diabetes. The presence of enterovirus (EV) in the pancreatic islets of these patients has previously been reported. Methods In the present study we used reverse transcription quantitative real-time PCR (RT-qPCR) and sequencing to characterise EV genomes present in different tissues to understand the nature of infection in these individuals. Results All six patients were found to be EV-positive by RT-qPCR in at least one of the tested sample types. Four patients were EV-positive in purified islet culture medium, three in PBMCs, one in duodenal biopsy and two in stool, while serum was EV-negative in all individuals. Sequencing the 5′ untranslated region of these EVs suggested that all but one belonged to enterovirus B species. One patient was EV-positive in all these sample types except for serum. Sequence analysis revealed that the virus strain present in the isolated islets of this patient was different from the strain found in other sample types. None of the islet-resident viruses could be isolated using EV-permissive cell lines. Conclusions/interpretation EV RNA can be frequently detected in various tissues of patients with type 1 diabetes. At least in some patients, the EV strain in the pancreatic islets may represent a slowly replicating persisting virus. Graphical abstract

scholarly journals One in Ten CD8+ Cells in the Pancreas of Living Individuals With Recent Onset Type 1 Diabetes Recognizes the Preproinsulin Epitope PPI15-24

2021 ◽  
Author(s):  
Ada Admin ◽  
Teresa Rodriguez-Calvo ◽  
Lars Krogvold ◽  
Natalie Amirian ◽  
Knut Dahl-Jørgensen ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cd8 T Cells ◽  
Pancreatic Tissue ◽  
Cell Reactivity ◽  
Tissue Samples ◽  
Recent Onset ◽  
Onset Type

In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with short and long disease duration. The Diabetes Virus Detection (DiViD) study collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset type 1 diabetes. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8+ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We additionally show the heterogeneity of islet distribution and CD8+ T cell infiltration. Our findings contribute to the current limited existing knowledge on T cell reactivity in the pancreas of recent onset type 1 diabetic donors, and indicate that antigen-specific therapies directed towards preproinsulin could have high clinical impact.

scholarly journals Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens

2021 ◽  
Author(s):  
Silke Smeets ◽  
Diedert Luc De Paep ◽  
Geert Stangé ◽  
Katrijn Verhaeghen ◽  
Bart Van der Auwera ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Cell ◽  
Age Groups ◽  
Pancreatic Tissue ◽  
Organ Donors ◽  
Tissue Samples ◽  
Increased Risk ◽  
Islet Cell Antigens

AbstractAutoantibodies against islet cell antigens are routinely used to identify subjects at increased risk of symptomatic type 1 diabetes, but their relation to the intra-islet pathogenetic process that leads to positivity for these markers is poorly understood. We screened 556 non-diabetic organ donors (3 months to 24 years) for five different autoantibodies and found positivity in 27 subjects, 25 single- and two double autoantibody-positive donors. Histopathological screening of pancreatic tissue samples showed lesion characteristic for recent-onset type 1 diabetes in the two organ donors with a high-risk profile, due to their positivity for multiple autoantibodies and HLA-inferred risk. Inflammatory infiltrates (insulitis) were found in a small fraction of islets (<5%) and consisted predominantly of CD3+CD8+ T-cells. Islets with insulitis were found in close proximity to islets devoid of insulin-positivity; such pseudo-atrophic islets were present in multiple small foci scattered throughout the pancreatic tissue or were found to be distributed with a lobular pattern. Relative beta cell area in both single and multiple autoantibody-positive donors was comparable to that in autoantibody-negative controls. In conclusion, in organ donors under age 25 years, insulitis and pseudo-atrophic islets were restricted to multiple autoantibody-positive individuals allegedly at high risk of developing symptomatic type 1 diabetes, in line with reports in older age groups. These observations may give further insight into the early pathogenetic events that may culminate in clinically overt disease.

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