Does a non-cytopathic viral infection of β cells initiate the disease process leading up to their autoimmune destruction?

1990 ◽  
Vol 3 (1) ◽  
pp. 65 ◽  
Author(s):  
Alan K. Foulis
Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 973
Author(s):  
Adrian Vlad ◽  
Viorel Serban ◽  
Romulus Timar ◽  
Alexandra Sima ◽  
Veronica Botea ◽  
...  

Background and Objective: It is known that several viruses are involved in the pathogenesis of type 1 diabetes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new worldwide spread virus that may act as a trigger for the autoimmune destruction of the β-cells, as well, and thus lead to an increase in the incidence of type 1 diabetes. Material and Methods: The Romanian National Organization for the Protection of Children and Adolescents with Diabetes (ONROCAD) has collected information regarding new cases of type 1 diabetes in children aged 0 to 14 years from all over the country since 1996 and has computed the incidence of type 1 diabetes in this age group. Results: We observed a marked increase in the incidence of type 1 diabetes in the first year of the COVID-19 pandemic, with 16.9%, from 11.4/100,000 in 2019 to 13.3/100,000 in 2020, much higher compared to previous years (mean yearly increase was 5.1% in the period 1996–2015 and 0.8% in the interval 2015–2019). The proportion of newly diagnosed cases was significantly higher in the second half of 2020 compared to the second half of the previous years (57.8 vs. 51%, p < 0.0001). Conclusions: All these aspects suggest the role that SARS-CoV-2 could have in triggering pancreatic autoimmunity. To confirm this, however, collecting information from larger populations from different geographical regions, monitoring the incidence curves over a period of several years, and gathering background information on COVID-19 and/or data on COVID-19 specific antibodies are needed.


2002 ◽  
Vol 11 (6) ◽  
pp. 519-528 ◽  
Author(s):  
Wilma L. Suarez-Pinzon ◽  
Yvonne Marcoux ◽  
Aziz Ghahary ◽  
Alex Rabinovitch

Nonobese diabetic (NOD) mice develop diabetes and destroy syngeneic islet grafts through an autoimmune response. Because transforming growth factor (TGF)-β1 downregulates immune responses, we tested whether overexpression of TGF-β1 by gene transfection of NOD mouse islets could protect β-cells in islet grafts from autoimmune destruction. NOD mouse islet cells were transfected with an adenoviral DNA expression vector encoding porcine latent TGF-β1 (Ad TGF- β1) or the adenoviral vector alone (control Ad vector). The frequency of total islet cells expressing TGF-1 protein was increased from 12±1% in control Ad vector-transfected cells to 89 ± 4% in Ad TGF-β1-transfected islet cells, and the frequency of β-cells that expressed TGF-β1 was increased from 12 ± 1% to 60 ± 7%. Also, secretion of TGF-β1 was significantly increased in islets that overexpressed TGF-β1. Ad TGF-β1-transfected NOD mouse islets that overexpressed TGF-β1 prevented diabetes recurrence after transplantation into diabetic NOD mice for a median of 22 days compared with only 7 days for control Ad vector-transfected islets (p = 0.001). Immunohistochemical examination of the islet grafts revealed significantly more TGF-β1+ cells and insulin+ cells and significantly fewer CD45+ leukocytes in Ad TGF-β1-transfected islet grafts. Also, islet β-cell apoptosis was significantly decreased whereas apoptosis of graft-infiltrating leukocytes was significantly increased in Ad TGF-β1-transfected islet grafts. These observations demonstrate that overexpression of TGF-β1, by gene transfection of NOD mouse islets, protects islet β-cells from apoptosis and autoimmune destruction and delays diabetes recurrence after islet transplantation.


2020 ◽  
Vol 295 (49) ◽  
pp. 16655-16664 ◽  
Author(s):  
Joshua D. Stafford ◽  
Zachary R. Shaheen ◽  
Chay Teng Yeo ◽  
John A. Corbett

Viral infection is one environmental factor that may contribute to the initiation of pancreatic β-cell destruction during the development of autoimmune diabetes. Picornaviruses, such as encephalomyocarditis virus (EMCV), induce a pro-inflammatory response in islets leading to local production of cytokines, such as IL-1, by resident islet leukocytes. Furthermore, IL-1 is known to stimulate β-cell expression of iNOS and production of the free radical nitric oxide. The purpose of this study was to determine whether nitric oxide contributes to the β-cell response to viral infection. We show that nitric oxide protects β-cells against virally mediated lysis by limiting EMCV replication. This protection requires low micromolar, or iNOS-derived, levels of nitric oxide. At these concentrations nitric oxide inhibits the Krebs enzyme aconitase and complex IV of the electron transport chain. Like nitric oxide, pharmacological inhibition of mitochondrial oxidative metabolism attenuates EMCV-mediated β-cell lysis by inhibiting viral replication. These findings provide novel evidence that cytokine signaling in β-cells functions to limit viral replication and subsequent β-cell lysis by attenuating mitochondrial oxidative metabolism in a nitric oxide–dependent manner.


2014 ◽  
Vol 222 (3) ◽  
pp. G13-G25 ◽  
Author(s):  
James E Bowe ◽  
Zara J Franklin ◽  
Astrid C Hauge-Evans ◽  
Aileen J King ◽  
Shanta J Persaud ◽  
...  

The pathophysiology of diabetes as a disease is characterised by an inability to maintain normal glucose homeostasis. In type 1 diabetes, this is due to autoimmune destruction of the pancreatic β-cells and subsequent lack of insulin production, and in type 2 diabetes it is due to a combination of both insulin resistance and an inability of the β-cells to compensate adequately with increased insulin release. Animal models, in particular genetically modified mice, are increasingly being used to elucidate the mechanisms underlying both type 1 and type 2 diabetes, and as such the ability to study glucose homeostasisin vivohas become an essential tool. Several techniques exist for measuring different aspects of glucose tolerance and each of these methods has distinct advantages and disadvantages. Thus the appropriate methodology may vary from study to study depending on the desired end-points, the animal model, and other practical considerations. This review outlines the most commonly used techniques for assessing glucose tolerance in rodents and details the factors that should be taken into account in their use. Representative scenarios illustrating some of the practical considerations of designingin vivoexperiments for the measurement of glucose homeostasis are also discussed.


Type 1 diabetes mellitus (T1D), one of the most chronic childhood disease, results from an autoimmune destruction of pancreatic β cells producing insulin, with insulin deficiency. Recently significant technological advances have been achieved in treatment and quality of life in diabetic patients but the causes are still uncertain, so it is still very difficult to foresee the possible prevention of this disease. The genetic factors alone do not explain the high risk of T1D, sharply increased over the last 40 years in Sardinia, with the second highest risk in the world after Finland, even as many of the people genetically predisposed to T1D do not develop the disease [1]. It is still unknown why some people develop T1D although it is agreed that genetic, non-genetic and probably epigenetic environmental factors all together contribute to the disease. The environmental factors are probably very important for both the development and the increase of T1D. The epigenetic factor possible interrelationships are to be cleared at most.


2020 ◽  
Vol 117 (49) ◽  
pp. 31219-31230
Author(s):  
Shanshan Tang ◽  
Mingfeng Zhang ◽  
Samuel Zeng ◽  
Yaxun Huang ◽  
Melissa Qin ◽  
...  

Type 1 diabetes (T1D) results from the autoimmune destruction of β cells, so cure of firmly established T1D requires both reversal of autoimmunity and restoration of β cells. It is known that β cell regeneration in nonautoimmune diabetic mice can come from differentiation of progenitors and/or transdifferentiation of α cells. However, the source of β cell regeneration in autoimmune nonobese diabetic (NOD) mice remains unclear. Here, we show that, after reversal of autoimmunity by induction of haploidentical mixed chimerism, administration of gastrin plus epidermal growth factor augments β cell regeneration and normalizes blood glucose in the firmly established diabetic NOD mice. Using transgenic NOD mice with inducible lineage-tracing markers for insulin-producing β cells, Sox9+ductal progenitors, Nestin+mesenchymal stem cells, and glucagon-producing α cells, we have found that both reactivation of dysfunctional low-level insulin expression (insulinlo) β cells and neogenesis contribute to the regeneration, with the latter predominantly coming from transdifferentiation of α cells. These results indicate that, after reversal of autoimmunity, reactivation of β cells and transdifferentiation of α cells can provide sufficient new functional β cells to reach euglycemia in firmly established T1D.


2017 ◽  
Vol 88 (5) ◽  
pp. 307-315 ◽  
Author(s):  
Mireia Fonolleda ◽  
Marta Murillo ◽  
Federico Vázquez ◽  
Joan Bel ◽  
Marta Vives-Pi

Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.


2009 ◽  
Vol 106 (37) ◽  
pp. 15768-15773 ◽  
Author(s):  
René Maehr ◽  
Shuibing Chen ◽  
Melinda Snitow ◽  
Thomas Ludwig ◽  
Lisa Yagasaki ◽  
...  

Type 1 diabetes (T1D) is the result of an autoimmune destruction of pancreatic β cells. The cellular and molecular defects that cause the disease remain unknown. Pluripotent cells generated from patients with T1D would be useful for disease modeling. We show here that induced pluripotent stem (iPS) cells can be generated from patients with T1D by reprogramming their adult fibroblasts with three transcription factors (OCT4, SOX2, KLF4). T1D-specific iPS cells, termed DiPS cells, have the hallmarks of pluripotency and can be differentiated into insulin-producing cells. These results are a step toward using DiPS cells in T1D disease modeling, as well as for cell replacement therapy.


2000 ◽  
Vol 12 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Janette Allison ◽  
Helen Thomas ◽  
Dianne Beck ◽  
Jamie L. Brady ◽  
Andrew M. Lew ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document