Enteroviruses and Type 1 Diabetes: Multiple Mechanisms and Factors?

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Richard E. Lloyd ◽  
Manasi Tamhankar ◽  
Åke Lernmark
Keyword(s):  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Subsequent Development ◽  
Annual Review ◽  
Publication Date ◽  
Virus Infections ◽  
Persistent Infections ◽  
Complex Interactions ◽  
Genetic And Environmental Factors

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Recent studies have strengthened the association between enteroviruses and development of autoimmunity in T1D patients, potentially through persistent infections. Enterovirus infections may contribute to different stages of disease development. We review data from both human cohort studies and experimental research exploring the potential roles and molecular mechanisms by which enterovirus infections can impact disease outcome. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Engineering β Cell Replacement Therapies for Type 1 Diabetes: Biomaterial Advances and Considerations for Macroscale Constructs

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Michelle J. Quizon ◽  
Andrés J. García
Keyword(s):  
Type 1 Diabetes ◽  
Cell Therapy ◽  
Therapeutic Modality ◽  
Annual Review ◽  
Publication Date ◽  
Β Cell ◽  
Cell Replacement ◽  
Clinical Islet Transplantation ◽  
Current Paradigm

While significant progress has been made in treatments for type 1 diabetes (T1D) based on exogenous insulin, transplantation of insulin-producing cells (islets or stem cell–derived β cells) remains a promising curative strategy. The current paradigm for T1D cell therapy is clinical islet transplantation (CIT)—the infusion of islets into the liver—although this therapeutic modality comes with its own limitations that deteriorate islet health. Biomaterials can be leveraged to actively address the limitations of CIT, including undesired host inflammatory and immune responses, lack of vascularization, hypoxia, and the absence of native islet extracellular matrix cues. Moreover, in efforts toward a clinically translatable T1D cell therapy, much research now focuses on developing biomaterial platforms at the macroscale, at which implanted platforms can be easily retrieved and monitored. In this review, we discuss how biomaterials have recently been harnessed for macroscale T1D β cell replacement therapies. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Coaggregation of Asthma and Type 1 Diabetes in Children: A Narrative Review

2021 ◽  
Vol 22 (11) ◽  
pp. 5757
Author(s):  
Laura Sgrazzutti ◽  
Francesco Sansone ◽  
Marina Attanasi ◽  
Sabrina Di Pillo ◽  
Francesco Chiarelli
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Molecular Mechanisms ◽  
Narrative Review ◽  
T Helper ◽  
Children With Asthma ◽  
Potential Link ◽  
Th 1 ◽  
Th1 And Th2

Asthma and type 1 diabetes mellitus (T1DM) are two of the most frequent chronic diseases in children, representing a model of the atopic and autoimmune diseases respectively. These two groups of disorders are mediated by different immunological pathways, T helper (Th)1 for diabetes and Th2 for asthma. For many years, these two groups were thought to be mutually exclusive according to the Th1/Th2 paradigm. In children, the incidence of both diseases is steadily increasing worldwide. In this narrative review, we report the evidence of the potential link between asthma and T1DM in childhood. We discuss which molecular mechanisms could be involved in the link between asthma and T1DM, such as genetic predisposition, cytokine patterns, and environmental influences. Cytokine profile of children with asthma and T1DM shows an activation of both Th1 and Th2 pathways, suggesting a complex genetic-epigenetic interaction. In conclusion, in children, the potential link between asthma and T1DM needs further investigation to improve the diagnostic and therapeutic approach to these patients. The aim of this review is to invite the pediatricians to consider the potential copresence of these two disorders in clinical practice.

COVID-19 and Diabetes

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Awadhesh Kumar Singh ◽  
Kamlesh Khunti
Keyword(s):  
Conclusive Evidence ◽  
Annual Review ◽  
Publication Date ◽  
Β Cells ◽  
Oral Antidiabetic Agents ◽  
Randomized Controlled ◽  
Conclusive Data ◽  
New Onset

The prevalence of diabetes in people with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has varied worldwide. Most of the available evidence suggests a significant increase in severity and mortality of COVID-19 in people with either type 1 (T1DM) or type 2 diabetes mellitus (T2DM), especially in association with poor glycemic control. While new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19 and have been associated with worse outcome, no conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the β cells of pancreatic islets. While all approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19, no conclusive data are yet available to indicate a mortality benefit with any class of these drugs, in the absence of large randomized controlled trials. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Immunotherapy: Building a bridge to a cure for type 1 diabetes

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. 510-516
Author(s):  
Jeffrey A. Bluestone ◽  
Jane H. Buckner ◽  
Kevan C. Herold
Keyword(s):  
Type 1 Diabetes ◽  
Immune Cell ◽  
Cell Types ◽  
Underlying Disease ◽  
Β Cells ◽  
Current State ◽  
Islet Inflammation ◽  
Genetic And Environmental Factors ◽  
Key Events

Type 1 diabetes (T1D) is an autoimmune disease in which T cells attack and destroy the insulin-producing β cells in the pancreatic islets. Genetic and environmental factors increase T1D risk by compromising immune homeostasis. Although the discovery and use of insulin have transformed T1D treatment, insulin therapy does not change the underlying disease or fully prevent complications. Over the past two decades, research has identified multiple immune cell types and soluble factors that destroy insulin-producing β cells. These insights into disease pathogenesis have enabled the development of therapies to prevent and modify T1D. In this review, we highlight the key events that initiate and sustain pancreatic islet inflammation in T1D, the current state of the immunological therapies, and their advantages for the treatment of T1D.

scholarly journals Glycosylation of CaV3.2 Channels Contributes to the Hyperalgesia in Peripheral Neuropathy of Type 1 Diabetes

2020 ◽  
Vol 14 ◽  
Author(s):  
Sonja Lj. Joksimovic ◽  
J. Grayson Evans ◽  
William E. McIntire ◽  
Peihan Orestes ◽  
Paula Q. Barrett ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Adult Female ◽  
Molecular Mechanisms ◽  
Sprague Dawley ◽  
Knock Out ◽  
Peripheral Diabetic Neuropathy ◽  
Novel Treatments

Our previous studies implicated glycosylation of the CaV3.2 isoform of T-type Ca2+ channels (T-channels) in the development of Type 2 painful peripheral diabetic neuropathy (PDN). Here we investigated biophysical mechanisms underlying the modulation of recombinant CaV3.2 channel by de-glycosylation enzymes such as neuraminidase (NEU) and PNGase-F (PNG), as well as their behavioral and biochemical effects in painful PDN Type 1. In our in vitro study we used whole-cell recordings of current-voltage relationships to confirm that CaV3.2 current densities were decreased ~2-fold after de-glycosylation. Furthermore, de-glycosylation induced a significant depolarizing shift in the steady-state relationships for activation and inactivation while producing little effects on the kinetics of current deactivation and recovery from inactivation. PDN was induced in vivo by injections of streptozotocin (STZ) in adult female C57Bl/6j wild type (WT) mice, adult female Sprague Dawley rats and CaV3.2 knock-out (KO mice). Either NEU or vehicle (saline) were locally injected into the right hind paws or intrathecally. We found that injections of NEU, but not vehicle, completely reversed thermal and mechanical hyperalgesia in diabetic WT rats and mice. In contrast, NEU did not alter baseline thermal and mechanical sensitivity in the CaV3.2 KO mice which also failed to develop painful PDN. Finally, we used biochemical methods with gel-shift analysis to directly demonstrate that N-terminal fragments of native CaV3.2 channels in the dorsal root ganglia (DRG) are glycosylated in both healthy and diabetic animals. Our results demonstrate that in sensory neurons glycosylation-induced alterations in CaV3.2 channels in vivo directly enhance diabetic hyperalgesia, and that glycosylation inhibitors can be used to ameliorate painful symptoms in Type 1 diabetes. We expect that our studies may lead to a better understanding of the molecular mechanisms underlying painful PDN in an effort to facilitate the discovery of novel treatments for this intractable disease.

scholarly journals ER stress and development of type 1 diabetes

2016 ◽  
Vol 64 (1) ◽  
pp. 2-6 ◽  
Author(s):  
Feyza Engin
Keyword(s):  
Type 1 Diabetes ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Adaptive Responses ◽  
Β Cell ◽  
Cellular Homeostasis ◽  
Unfolded Protein

Type 1 diabetes (T1D) results from an autoimmune-mediated destruction of pancreatic β cells. The incidence of T1D is on the rise globally around 3% to 5% per year and rapidly increasing incidence in younger children is of the greatest concern. currently, there is no way to cure or prevent T1D; hence, a deeper understanding of the underlying molecular mechanisms of this disease is essential to the development of new effective therapies. The endoplasmic reticulum (ER) is an organelle with multiple functions that are essential for cellular homeostasis. Excessive demand on the ER, chronic inflammation, and environmental factors lead to ER stress and to re-establish cellular homeostasis, the adaptive unfolded protein response (UPR) is triggered. However, chronic ER stress leads to a switch from a prosurvival to a proapoptotic UPR, resulting in cell death. Accumulating data have implicated ER stress and defective UPR in the pathogenesis of inflammatory and autoimmune diseases, and ER stress has been implicated in β-cell failure in type 2 diabetes. However, the role of ER stress and the UPR in β-cell pathophysiology and in the initiation and propagation of the autoimmune responses in T1D remains undefined. This review will highlight the current understanding and recent in vivo data on the role of ER stress and adaptive responses in T1D pathogenesis and the potential therapeutic aspect of enhancing β-cell ER function and restoring UPR defects as novel clinical strategies against this disease.

Molecular Force Measurement with Tension Sensors

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Lisa S. Fischer ◽  
Srishti Rangarajan ◽  
Tanmay Sadhanasatish ◽  
Carsten Grashoff
Keyword(s):  
Molecular Mechanisms ◽  
Force Measurement ◽  
Annual Review ◽  
Publication Date ◽  
Mechanical Forces ◽  
Biophysical Parameters ◽  
Cellular Mechanotransduction ◽  
Molecular Force ◽  
Molecular Forces ◽  
Physical Principles

The ability of cells to generate mechanical forces, but also to sense, adapt to, and respond to mechanical signals, is crucial for many developmental, postnatal homeostatic, and pathophysiological processes. However, the molecular mechanisms underlying cellular mechanotransduction have remained elusive for many decades, as techniques to visualize and quantify molecular forces across individual proteins in cells were missing. The development of genetically encoded molecular tension sensors now allows the quantification of piconewton-scale forces that act upon distinct molecules in living cells and even whole organisms. In this review, we discuss the physical principles, advantages, and limitations of this increasingly popular method. By highlighting current examples from the literature, we demonstrate how molecular tension sensors can be utilized to obtain access to previously unappreciated biophysical parameters that define the propagation of mechanical forces on molecular scales. We discuss how the methodology can be further developed and provide a perspective on how the technique could be applied to uncover entirely novel aspects of mechanobiology in the future. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Lihe Chen ◽  
Hyun Jun Jung ◽  
Arnab Datta ◽  
Euijung Park ◽  
Brian G. Poll ◽  
...  
Keyword(s):  
Systems Biology ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Water Channel ◽  
Peptide Hormone ◽  
Annual Review ◽  
Publication Date ◽  
Large Scale Data ◽  
V2 Receptor ◽  
Scale Data

Systems biology can be defined as the study of a biological process in which all of the relevant components are investigated together in parallel to discover the mechanism. Although the approach is not new, it has come to the forefront as a result of genome sequencing projects completed in the first few years of the current century. It has elements of large-scale data acquisition (chiefly next-generation sequencing–based methods and protein mass spectrometry) and large-scale data analysis (big data integration and Bayesian modeling). Here we discuss these methodologies and show how they can be applied to understand the downstream effects of GPCR signaling, specifically looking at how the neurohypophyseal peptide hormone vasopressin, working through the V2 receptor and PKA activation, regulates the water channel aquaporin-2. The emerging picture provides a detailed framework for understanding the molecular mechanisms involved in water balance disorders, pointing the way to improved treatment of both polyuric disorders and water-retention disorders causing dilutional hyponatremia. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

MicroRNAs and Diabetes Mellitus Type 1

2021 ◽  
Vol 17 ◽  
Author(s):  
Farbod Bahreini ◽  
Elham Rayzan ◽  
Nima Rezaei
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Early Detection ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Islet Cells ◽  
Diabetes Mellitus Type 1 ◽  
Complementary Sequence ◽  
Multiple Organs

: Type 1 diabetes mellitus is a multifactorial, progressive, autoimmune disease with a strong genetic feature that can affect multiple organs, including kidney, eyes, and nerves. Early detection of type 1 diabetes can help critically to avoid serious damages to these organs. MicroRNAs are small RNA molecules that act in post-transcriptional gene regulation by attaching to the complementary sequence in the 3'-untranslated region of their target genes. Alterations in the expression of microRNA coding genes are extensively reported in several diseases such as type 1 diabetes. Presenting non-invasive biomarkers for early detection of type 1 diabetes by quantifying microRNAs gene expression level can be an influential step in biotechnology and medicine. This review discusses the area of microRNAs dysregulation in type 1 diabetes and affected molecular mechanisms involved in pancreatic islet cells formation and dysregulation in the expression of inflammatory elements as well as pro-inflammatory cytokines.

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