scholarly journals Influence of Vitamin D on Islet Autoimmunity and Beta-Cell Function in Type 1 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2185 ◽  
Author(s):  
Marco Infante ◽  
Camillo Ricordi ◽  
Janine Sanchez ◽  
Michael J. Clare-Salzler ◽  
Nathalia Padilla ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Vitamin D Deficiency ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Current Knowledge ◽  
Islet Autoimmunity ◽  
Immunomodulatory Effects

Type 1 diabetes (T1D) is a chronic autoimmune disease leading to immune-mediated destruction of pancreatic beta cells, resulting in the need for insulin therapy. The incidence of T1D is increasing worldwide, thus prompting researchers to investigate novel immunomodulatory strategies to halt autoimmunity and modify disease progression. T1D is considered as a multifactorial disease, in which genetic predisposition and environmental factors interact to promote the triggering of autoimmune responses against beta cells. Over the last decades, it has become clear that vitamin D exerts anti-inflammatory and immunomodulatory effects, apart from its well-established role in the regulation of calcium homeostasis and bone metabolism. Importantly, the global incidence of vitamin D deficiency is also dramatically increasing and epidemiologic evidence suggests an involvement of vitamin D deficiency in T1D pathogenesis. Polymorphisms in genes critical for vitamin D metabolism have also been shown to modulate the risk of T1D. Moreover, several studies have investigated the role of vitamin D (in different doses and formulations) as a potential adjuvant immunomodulatory therapy in patients with new-onset and established T1D. This review aims to present the current knowledge on the immunomodulatory effects of vitamin D and summarize the clinical interventional studies investigating its use for prevention or treatment of T1D.

scholarly journals Vitamin D and diabetes mellitus: an update 2013

2014 ◽  
Vol 58 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Luiz Henrique Maciel Griz ◽  
Francisco Bandeira ◽  
Mônica Andrade Lima Gabbay ◽  
Sergio Atala Dib ◽  
Eduardo Freese de Carvalho
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Vitamin D Deficiency ◽  
Pancreatic Beta Cells ◽  
Increased Risk ◽  
Geographical Regions

Vitamin D deficiency and diabetes mellitus are two common conditions and they are widely prevalent across all ages, races, geographical regions, and socioeconomic conditions. Epidemiologic studies have shown association of vitamin D deficiency and increased risk of chronic diseases, such as cancer, cardiovascular disease, type 2 diabetes, and autoimmune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The identification of 1,25(OH)2D receptors and 1-α-hydroxilase expression in pancreatic beta cells, in cells of the immune system, and in various others tissues, besides the bone system support the role of vitamin D in the pathogenesis of type 2 diabetes. Observational studies have revealed an association between 25(OH) D deficiency and the prevalence of type 1 diabetes in children and adolescents. This review will focus on the concept of vitamin D deficiency, its prevalence, and its role in the pathogenesis and risk of diabetes mellitus and cardiovascular diseases.

scholarly journals Serum vitamin D deficiency in children and adolescents is associated with type 1 diabetes mellitus

2018 ◽  
Vol 7 (12) ◽  
pp. 1275-1279 ◽  
Author(s):  
Changwei Liu ◽  
Jingwen Wang ◽  
Yuanyuan Wan ◽  
Xiaona Xia ◽  
Jian Pan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Vitamin D ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Vitamin D Deficiency ◽  
Newly Diagnosed ◽  
25Ohd Level ◽  
Serum 25Ohd ◽  
The Mean

Background To investigate the relationship 25-hydroxy vitamin D (25OHD) level among children and in children with type 1 diabetes mellitus (T1DM). Methods A case–control study was conducted to compare the serum 25OHD levels between cases and controls. This study recruited 296 T1DM children (106 newly diagnosed T1DM patients and 190 established T1DM patients), and 295 age- and gender-matched healthy subjects as controls. Results The mean serum 25OHD in T1DM children was 48.69 ± 15.26 nmol/L and in the controls was 57.93 ± 19.03 nmol/L. The mean serum 25OHD in T1DM children was lower than that of controls (P < 0.01). The mean serum 25OHD level (50.42 ± 14.74 nmol/L) in the newly diagnosed T1DM children was higher than that (47.70 ± 15.50 nmol/L) in the established T1DM children but the difference was not statistically significant (P = 0.16). HbA1c values were associated with 25OHD levels in established T1DM children (r = 0.264, P < 0.01), and there was no association between 25OHD and HbA1c in newly diagnosed T1DM children (r = 0.164; P > 0.05). Conclusion Vitamin D deficiency is common in T1DM children, and it should be worthy of attention on the lack of vitamin D in established T1DM children.

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 Hubungan Paparan Sinar Matahari, Status Gizi, dan Asupan Makan terhadap Kadar Vitamin D Anak dan Remaja Penderita Diabetes Mellitus Tipe 1

2021 ◽  
Vol 5 (1) ◽  
pp. 41
Author(s):  
Inggita Kusumastuty ◽  
Dian Handayani ◽  
Harjoedi Adji Tjahjono ◽  
Elsa Permata Sari ◽  
Silvy Kartika Rahayuningtyas ◽  
...  
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Food Intake ◽  
Nutritional Status ◽  
Children And Adolescents ◽  
Vitamin D Deficiency ◽  
Protein Intake ◽  
Sunlight Exposure ◽  
Vitamin D Levels

Background: Previous research state the correlation between vitamin D deficiency and Type 1 diabetes. The deficiency of Vitamin D is caused by vitamin D intake, sunlight exposure, or nutritional status. Indonesia, as a tropical country, is close to the equator and receives sunlight all year long. Little research has been done on vitamin D levels in children and adolescents with Type 1 Diabetes in Indonesia.Objective: The study aims to determine the relationship among sunlight exposure, nutritional status, food intake, and vitamin D levels in children and adolescents with Type 1 Diabetes.Methods: The study design was cross-sectional with a sample size of 31 children and adolescents aged 5-19 years. Sunlight exposure data were collected using the Sun Exposure Questionnaire form, nutritional status o BMI/age data were using the WHO Anthro, food intake data were using the Semi-Quantitative Food Frequency Questioner, and vitamin D level data were using the ELISA method. Statistical analysis was conducted by using SPSS Version 21 with Pearson and Spearman correlation test.Results: All respondents showed vitamin D deficiency. Most respondents had low sunlight exposure and nutritional status in the normoweight category. The majority of respondents had good energy and protein intake, excess fat, low carbohydrates, and low vitamin D and calcium.Conclusion:There is a positive relationship between sunlight exposure and vitamin D level (p = 0.001, r = 0.627). However, there is no relationship among nutritional status, protein intake, fat, carbohydrates, vitamin D and calcium on the level of vitamin D (p = 0.409; p = 0.240; p = 0.311; p = 0.822; p = 0.231; 0.382).

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.

scholarly journals miRNA142-3p targets Tet2 and impairs Treg differentiation and stability in models of type 1 diabetes

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Martin G. Scherm ◽  
Isabelle Serr ◽  
Adam M. Zahm ◽  
Jonathan Schug ◽  
Saverio Bellusci ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
T Cell Activation ◽  
Pancreatic Beta Cells ◽  
Cell Activation ◽  
Clinical Symptoms ◽  
Mechanistic Model ◽  
Treg Cells ◽  
Islet Autoimmunity ◽  
Molecular Approaches

AbstractIn type 1 diabetes, the appearance of islet autoantibodies indicates the onset of islet autoimmunity, often many years before clinical symptoms arise. While T cells play a major role in the destruction of pancreatic beta cells, molecular underpinnings promoting aberrant T cell activation remain poorly understood. Here, we show that during islet autoimmunity an miR142-3p/Tet2/Foxp3 axis interferes with the efficient induction of regulatory T (Treg) cells, resulting in impaired Treg stability in mouse and human. Specifically, we demonstrate that miR142-3p is induced in islet autoimmunity and that its inhibition enhances Treg induction and stability, leading to reduced islet autoimmunity in non-obese diabetic mice. Using various cellular and molecular approaches we identify Tet2 as a direct target of miR142-3p, thereby linking high miR142-3p levels to epigenetic remodeling in Tregs. These findings offer a mechanistic model where during islet autoimmunity miR142-3p/Tet2-mediated Treg instability contributes to autoimmune activation and progression.

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