scholarly journals The Prime Cause of type-2 (T2D), Type-1 Diabetes (T1D) And The Relation Between Diabetes and Cancer

2019 ◽  
Author(s):  
Sorush Niknamian
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Beta Cells ◽  
Stress Responses ◽  
Pancreatic Beta Cells ◽  
Physiological Effect ◽  
Bohr Effect ◽  
Evolutionary Mechanisms ◽  
Treatment And Prevention

Diabetes mellitus (DM) is a group of metabolic disorders in which there are high blood sugar levels over a prolonged period. Between 1985 and 2002, the number of people with diabetes grew from 30 million to 217 million, and this incidence will be expected to exceed 366 million by 2030. Type 1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. This research has gone through several important reviews plus one research on 21 mice which is done in Violet Cancer Institute (VCI) to find the prime reason behind T1D and T2D. We have reviewed the physiological and evolutionary mechanisms in both types of diabetes. In all cases, Hypoxia through Bohr Effect have been observed. The Bohr effect increases the efficiency of oxygen transportation through the blood. After hemoglobin binds to oxygen in the lungs because of the high oxygen concentrations, the Bohr effect facilitates its release in the tissues, specifically those tissues which need the most oxygen. Chronic hypoxia in tissues and pancreatic beta-cells through the Bohr Effect (BE) has been discussed in this review/research as the reason for causing T2D and T1D. HIF-1alpha regulates cellular stress responses, While the levels of HIF-1alpha protein are tightly regulated, it can be active under normoxic conditions, Dysregulation may contribute to the pathogenesis of T2D and sudden hypoxia in pancreatic beta-cells through BE which is is the prime cause of T1D which can be of good help for researchers to focus on this physiological effect for the treatment and prevention of these two diseases. Additionally, we have discussed the main relation between diabetes and cancer in this research as well.

scholarly journals Nano-curcumin safely prevents streptozotocin-induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus

2017 ◽  
Vol 174 (13) ◽  
pp. 2074-2084 ◽  
Author(s):  
Raghu Ganugula ◽  
Meenakshi Arora ◽  
Patcharawalai Jaisamut ◽  
Ruedeekorn Wiwattanapatapee ◽  
Heather G Jørgensen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Effective Management

scholarly journals The role of apoptosis in pathogenesis of type 1 diabetes mellitus

2010 ◽  
Vol 13 (1) ◽  
pp. 45-49
Author(s):  
Elena Vladimirovna Pekareva ◽  
Tatiana Vasil'evna Nikonova ◽  
Olga Mikhailovna Smirnova
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Beta Cell ◽  
Type 1 Diabetes Mellitus ◽  
Beta Cells ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cells ◽  
Beta Cell Apoptosis

Type 1 diabetes mellitus (DM1) is known to be associated with progressive destruction of pancreatic beta-cells. Apoptosis plays the key role in this destructiveprocess. The paper focuses on major mechanisms underlying activation of beta-cell apoptosis and its role in regulation of immune processes inpatients with DM1.

scholarly journals Replacing murine insulin 1 with human insulin protects NOD mice from diabetes

2019 ◽  
Author(s):  
Colleen M. Elso ◽  
Nicholas A. Scott ◽  
Lina Mariana ◽  
Emma I. Masterman ◽  
Andrew P.R. Sutherland ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Mouse Models ◽  
Human Insulin ◽  
Murine Model ◽  
Pancreatic Beta Cells ◽  
Autoimmune Diabetes ◽  
Nod Mice ◽  
Human Type 1 Diabetes

AbstractType 1, or autoimmune, diabetes is caused by the T-cell mediated destruction of the insulin-producing pancreatic beta cells. Non-obese diabetic (NOD) mice spontaneously develop autoimmune diabetes akin to human type 1 diabetes. For this reason, the NOD mouse has been the preeminent murine model for human type 1 diabetes research for several decades. However, humanized mouse models are highly sought after because they offer both the experimental tractability of a mouse model and the clinical relevance of human-based research. Autoimmune T-cell responses against insulin, and its precursor proinsulin, play central roles in the autoimmune responses against pancreatic beta cells in both humans and NOD mice. As a first step towards developing a murine model of the human autoimmune response against pancreatic beta cells we set out to replace the murine insulin 1 gene (Ins1) with the human insulin gene (INS) using CRISPR/Cas9. Here we describe a NOD mouse strain that expresses human insulin in place of murine insulin 1, referred to as HuPI. HuPI mice express human insulin, and C-peptide, in their serum and pancreata and have normal glucose tolerance. Compared with wild type NOD mice, the incidence of diabetes is much lower in HuPI mice. Only 15-20% of HuPI mice developed diabetes after 300 days, compared to more than 60% of unmodified NOD mice. Immune-cell infiltration into the pancreatic islets of HuPI mice was not detectable at 100 days but was clearly evident by 300 days. This work highlights the feasibility of using CRISPR/Cas9 to create mouse models of human diseases that express proteins pivotal to the human disease. Furthermore, it reveals that even subtle changes in proinsulin protect NOD mice from diabetes.

scholarly journals Similarities Between Bacterial GAD and Human GAD65: Implications in Gut Mediated Autoimmune Type 1 Diabetes

2021 ◽  
Author(s):  
Monica Westley ◽  
Tiffany Richardson ◽  
Suhana Bedi ◽  
Baofeng Jia ◽  
Fiona S.L. Brinkman ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Gut Microbiome ◽  
Pancreatic Beta Cells ◽  
Acid Decarboxylase ◽  
Host Immune System ◽  
Gamma Aminobutyric Acid ◽  
Human Gut ◽  
Autoimmune Attack

Abstract    A variety of islet autoantibodies (AAbs) can predict and possibly dictate eventual type 1 diabetes (T1D) diagnosis. Upwards of 75% of those with T1D are positive for AAbs against glutamic acid decarboxylase (GAD65), a producer of gamma-aminobutyric acid (GABA) in human pancreatic beta cells. Interestingly, bacterial populations within the human gut also express GAD65 and produce GABA. Evidence suggests that dysbiosis of the microbiome may correlate with T1D pathogenesis and physiology. Therefore, autoimmune linkages between the gut microbiome and islets susceptible to autoimmune attack need to be further elucidated. Utilizing silico analyses, we show here that 25 GAD sequences from different human gut bacterial sources show sequence and motif similarities to human beta cell GAD65. Our motif analyses determined that a majority of gut GAD sequences contain the pyroxical dependent decarboxylase domain of human GAD65 which is important for its enzymatic activity. Additionally, we showed overlap with known human GAD65 T-cell receptor epitopes which may implicate the immune destruction of beta cells. Thus, we propose a physiological hypothesis in which changes in the gut microbiome in those with T1D result in a release of bacterial GAD, thus causing miseducation of the host immune system. Due to the notable similarities, we found between humans and bacterial GAD, these deputized immune cells may then go on to target human beta cells leading to the development of T1D.

scholarly journals Peroxiredoxin 6 Attenuates Alloxan-Induced Type 1 Diabetes Mellitus in Mice and Cytokine-Induced Cytotoxicity in RIN-m5F Beta Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Elena G. Novoselova ◽  
Olga V. Glushkova ◽  
Sergey M. Lunin ◽  
Maxim O. Khrenov ◽  
Svetlana B. Parfenyuk ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Cell Apoptosis ◽  
Pancreatic Beta Cells ◽  
Apoptotic Cell ◽  
Main Idea ◽  
Severe Form ◽  
Peroxiredoxin 6 ◽  
Cells Cultured

Type 1 diabetes is associated with the destruction of pancreatic beta cells, which is mediated via an autoimmune mechanism and consequent inflammatory processes. In this article, we describe a beneficial effect of peroxiredoxin 6 (PRDX6) in a type 1 diabetes mouse model. The main idea of this study was based on the well-known data that oxidative stress plays an important role in pathogenesis of diabetes and its associated complications. We hypothesised that PRDX6, which is well known for its various biological functions, including antioxidant activity, may provide an antidiabetic effect. It was shown that PRDX6 prevented hyperglycemia, lowered the mortality rate, restored the plasma cytokine profile, reversed the splenic cell apoptosis, and reduced the β cell destruction in Langerhans islets in mice with a severe form of alloxan-induced diabetes. In addition, PRDX6 protected rat insulinoma RIN-m5F β cells, cultured with TNF-α and IL-1β, against the cytokine-induced cytotoxicity and reduced the apoptotic cell death and production of ROS. Signal transduction studies showed that PRDX6 prevented the activation of NF-κB and c-Jun N-terminal kinase signaling cascades in RIN-m5F β cells cultured with cytokines. In conclusion, there is a prospect for therapeutic application of PRDX6 to delay or even prevent β cell apoptosis in type 1 diabetes.

Prospects of antigen-specific therapy in type 1 diabetes mellitus

2012 ◽  
Vol 15 (4) ◽  
pp. 28-32
Author(s):  
Tatiana Vasil'evna Nikonova ◽  
Yulia Viktorovna Alekseeva
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Pancreatic Beta Cells ◽  
Large Scale ◽  
Specific Immunotherapy ◽  
Preventive Measures ◽  
Therapeutic Agents ◽  
Specific Therapy

Type 1 diabetes mellitus is commonly recognized as an autoimmune disease characterized by progressive destruction of pancreatic ?-beta-cells. Progress in diagnostics at preclinical stage is accompanied with active development of preventive measures. So far, there are no specific therapeutic agents approved for clinical practice. However, ongoing large-scale studies have outlined some promising solutions, antigen-specific immunotherapy being one of them.

scholarly journals Beta Cell Autophagy in the Pathogenesis of Type 1 Diabetes

2021 ◽  
Author(s):  
Charanya Muralidharan ◽  
Amelia K Linnemann
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Potential Role ◽  
Cell Dysfunction ◽  
Unconventional Secretion ◽  
Insulin Dependent

Type 1 diabetes is an insulin-dependent, autoimmune disease where the pancreatic beta cells are destroyed resulting in hyperglycemia. This multi-factorial disease involves multiple environmental and genetic factors, and has no clear etiology. Accumulating evidence suggests that early signaling defects within the beta cells may promote a change in the local immune mileu, contributing to autoimmunity. Therefore, many studies have been focused on intrinsic beta cell mechanisms that aid in restoration of cellular homeostasis under environmental conditions that cause dysfunction. One of these intrinsic mechanisms to promote homeostasis is autophagy, defects in which are clearly linked with beta cell dysfunction in the context of type 2 diabetes. Recent studies have now also pointed towards beta cell autophagy defects in the context of type 1 diabetes. In this perspectives review, we will discuss the evidence supporting a role for beta cell autophagy in the pathogenesis of type 1 diabetes, including a potential role for unconventional secretion of autophagosomes/lysosomes in the changing dialogue between the beta cell and immune cells.

scholarly journals BET Proteins Are Required for Transcriptional Activation of the Senescent Islet Cell Secretome in Type 1 Diabetes

2019 ◽  
Vol 20 (19) ◽  
pp. 4776 ◽  
Author(s):  
Peter J. Thompson ◽  
Ajit Shah ◽  
Hara Apostolopolou ◽  
Anil Bhushan
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Transcriptional Activation ◽  
Pancreatic Beta Cells ◽  
Islet Cells ◽  
Disease Onset ◽  
Protein Inhibition ◽  
Bet Protein

Type 1 diabetes (T1D) results from the progressive loss of pancreatic beta cells as a result of autoimmune destruction. We recently reported that during the natural history of T1D in humans and the female nonobese diabetic (NOD) mouse model, beta cells acquire a senescence-associated secretory phenotype (SASP) that is a major driver of disease onset and progression, but the mechanisms that activate SASP in beta cells were not explored. Here, we show that the SASP in islet cells is transcriptionally controlled by Bromodomain ExtraTerminal (BET) proteins, including Bromodomain containing protein 4 (BRD4). A chromatin analysis of key beta cell SASP genes in NOD islets revealed binding of BRD4 at active regulatory regions. BET protein inhibition in NOD islets diminished not only the transcriptional activation and secretion of SASP factors, but also the non-cell autonomous activity. BET protein inhibition also decreased the extent of SASP induction in human islets exposed to DNA damage. The BET protein inhibitor iBET-762 prevented diabetes in NOD mice and also attenuated SASP in islet cells in vivo. Taken together, our findings support a crucial role for BET proteins in the activation of the SASP transcriptional program in islet cells. These studies suggest avenues for preventing T1D by transcriptional inhibition of SASP.

Upregulation of HLA class II in pancreatic beta cells from organ donors with type 1 diabetes

Diabetologia ◽  
2021 ◽  
Author(s):  
Estefania Quesada-Masachs ◽  
Samuel Zilberman ◽  
Sakthi Rajendran ◽  
Tiffany Chu ◽  
Sara McArdle ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Class Ii ◽  
Hla Class Ii ◽  
Organ Donors
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