Type 1 Diabetes: Causes, Symptoms and Treatments, Review with Personal Experience
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Type 1 Diabetes Autoantigen Epitope in the Pathogenesis of Junction of Proinsulin Is an Early Evidence That a Peptide Spanning T
Evidence That a Peptide Spanning the B-C Junction of Proinsulin Is an Early Autoantigen Epitope in the Pathogenesis of Type 1 Diabetes This information is current as of September 24, 2021. Wei Chen, Isabelle Bergerot, John F. Elliott, Leonard C. Harrison, Norio Abiru, George S. Eisenbarth and Terry L. Delovitch J Immunol 2001; 167:4926-4935; ; doi: 10.4049/jimmunol.167.9.4926 Downloaded from http://www.jimmunol.org/content/167/9/4926 References This article cites 50 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/167/9/4926.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 24, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Evidence That a Peptide Spanning the B-C Junction of Proinsulin Is an Early Autoantigen Epitope in the Pathogenesis of Type 1 Diabetes1 Wei Chen,2* Isabelle Bergerot,2* John F. -
Diabetes Is a Disease in Which the Body's Ability to Produce Or Respond
Early Signs and Symptoms of diabetes: Early symptoms of diabetes, especially type 2 diabetes, can be subtle or seemingly harmless. Over time, however, you may Diabetes is a disease in which the develop diabetes complications, even if you body’s ability to produce or respond to haven't had diabetes symptoms. In the the hormone insulin is impaired, United States alone, more than 8 million resulting in abnormal metabolism of people have undiagnosed diabetes, Treatments: carbohydrates and elevated levels of according to the American Diabetes Association. Understanding possible glucose (sugar) in the blood. • Insulin therapy diabetes symptoms can lead to early • Oral medications diagnosis and treatment and a lifetime of Diabetes can be broken down into • better health. If you're experiencing any of Diet changes two types, Type 1 and Type 2. Type 1 • Exercise diabetes involves the the following diabetes signs and symptoms, see your doctor. body attacking itself by The medications you take vary by mistake, this then the type of diabetes and how well the causes the body to stop making insulin. With medicine controls you blood glucose levels. Type 2 diabetes the Type 1 diabetics must have insulin. Type 2 body does not respond may or may not include insulin and may just like it should to the be controlled with diet and exercise alone. insulin the pancreas is If you notice any of these changes notify making. Your body tells the pancreas that it needs to make more insulin since the your health care provider. The earlier • insulin that is already there is not working. -
Type 1 Diabetes and Celiac Disease: Overview and Medical Nutrition Therapy
Nutrition FYI Type 1 Diabetes and Celiac Disease: Overview and Medical Nutrition Therapy Sarah Jane Schwarzenberg, MD, and Carol Brunzell, RD, CDE In patients with celiac disease (gluten- problems recognized only retrospec- glycemia, but only several months sensitive enteropathy, or GSE), inges- tively as resulting from celiac disease; after initiation. tion of the gliadin fraction of wheat it is common for “asymptomatic” It seems likely that a malabsorp- gluten and similar molecules (pro- patients to report improved health or tive disease could create opportunity lamins) from barley, rye, and possibly sense of well-being when following a for hypoglycemia in diabetes, partic- oats causes damage to the intestinal gluten-free diet. Up to one-third of ularly in patients under tight control. epithelium. The injury results from an patients may have unexplained failure Serological testing for GSE in abnormal T-cell response against to thrive, abdominal pain, or short patients with type 1 diabetes, with gliadin. Thus, GSE is a disease in stature.3,6 early diagnosis of GSE, may reduce which host susceptibility must be More controversial is the question this risk by allowing patients to be combined with a specific environmen- of whether GSE affects blood glucose diagnosed in a pre-symptomatic tal trigger to affect injury.1 control. A study by Acerini et al.7 in a state. It also seems prudent to closely Typically, patients with GSE have type 1 diabetic population found no monitor insulin needs and blood glu- chronic diarrhea and failure to thrive. difference between the celiac and non- cose control during the early phase of However, some patients present with celiac subpopulation in terms of instituting a gluten-free diet. -
Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface
Hindawi Publishing Corporation Journal of Diabetes Research Volume 2016, Article ID 6179635, 4 pages http://dx.doi.org/10.1155/2016/6179635 Research Article Sulfatide Preserves Insulin Crystals Not by Being Integrated in the Lattice but by Stabilizing Their Surface Karsten Buschard,1 Austin W. Bracey,2 Daniel L. McElroy,2 Andrew T. Magis,2 Thomas Osterbye,1 Mark A. Atkinson,2 Kate M. Bailey,2 Amanda L. Posgai,2 and David A. Ostrov2 1 Bartholin Instituttet, Rigshospitalet, 2100 Copenhagen, Denmark 2Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, 1600 SW Archer Road, Gainesville, FL 32610, USA Correspondence should be addressed to Karsten Buschard; [email protected] Received 30 October 2015; Revised 14 January 2016; Accepted 14 January 2016 Academic Editor: Fabrizio Barbetti Copyright © 2016 Karsten Buschard et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Sulfatide is known to chaperone insulin crystallization within the pancreatic beta cell, but it is not known if this results from sulfatide being integrated inside the crystal structure or by binding the surface of the crystal. With this study, we aimed to characterize the molecular mechanisms underlying the integral role for sulfatide in stabilizing insulin crystals prior to exocytosis. Methods. We cocrystallized human insulin in the presence of sulfatide and solved the structure by molecular replacement. Results. The crystal structure of insulin crystallized in the presence of sulfatide does not reveal ordered occupancy representing sulfatide in the crystal lattice, suggesting that sulfatide does not permeate the crystal lattice but exerts its stabilizing effect by alternative interactions such as on the external surface of insulin crystals. -
Prediabetes: What Is It and What Can I Do?
Prediabetes: What Is It and What Can I Do? What is prediabetes? Weight loss can delay or prevent diabetes. Prediabetes is a condition that comes before Reaching a healthy weight can help you a lot. diabetes. It means your blood glucose levels are If you’re overweight, any weight loss, even higher than normal but aren’t high enough to be 7 percent of your weight (for example, losing called diabetes. about 15 pounds if you weigh 200), may lower your risk for diabetes. There are no clear symptoms of prediabetes. You can have it and not know it. If I have prediabetes, what does it mean? It means you might get type 2 diabetes soon or down the road. You are also more likely to get heart disease or have a stroke. The good news is that you can take steps to delay or prevent type 2 diabetes. How can I delay or prevent type 2 diabetes? You may be able to delay or prevent type 2 diabetes with: Daily physical activity, such as walking. Weight loss, if needed. Losing even a few pounds will help. Medication, if your doctor prescribes it. If you have prediabetes, these steps may bring your blood glucose to a normal range. But you are still at a higher risk for type 2 diabetes. Regular physical activity can delay or prevent diabetes. Being active is one of the best ways to delay or prevent type 2 diabetes. It can also lower your weight and blood pressure, and improve cholesterol levels. Ask your health care team about activities that are safe for you. -
Isolation and Proteomics of the Insulin Secretory Granule
H OH metabolites OH Review Isolation and Proteomics of the Insulin Secretory Granule Nicholas Norris , Belinda Yau * and Melkam Alamerew Kebede Charles Perkins Centre, School of Medical Sciences, University of Sydney, Camperdown, NSW 2006, Australia; [email protected] (N.N.); [email protected] (M.A.K.) * Correspondence: [email protected] Abstract: Insulin, a vital hormone for glucose homeostasis is produced by pancreatic beta-cells and when secreted, stimulates the uptake and storage of glucose from the blood. In the pancreas, insulin is stored in vesicles termed insulin secretory granules (ISGs). In Type 2 diabetes (T2D), defects in insulin action results in peripheral insulin resistance and beta-cell compensation, ultimately leading to dysfunctional ISG production and secretion. ISGs are functionally dynamic and many proteins present either on the membrane or in the lumen of the ISG may modulate and affect different stages of ISG trafficking and secretion. Previously, studies have identified few ISG proteins and more recently, proteomics analyses of purified ISGs have uncovered potential novel ISG proteins. This review summarizes the proteins identified in the current ISG proteomes from rat insulinoma INS-1 and INS-1E cell lines. Here, we also discuss techniques of ISG isolation and purification, its challenges and potential future directions. Keywords: insulin secretory granule; beta-cells; granule protein purification 1. Insulin Granule Biogenesis and Function Citation: Norris, N.; Yau, B.; Kebede, The insulin secretory granule (ISG) is the storage vesicle for insulin in pancreatic M.A. Isolation and Proteomics of the beta-cells. It was long treated as an inert carrier for insulin but is now appreciated as a Insulin Secretory Granule. -
Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes
258 Diabetes Care Volume 42, February 2019 Proinsulin Secretion Is a Emily K. Sims,1,2 Henry T. Bahnson,3 Julius Nyalwidhe,4 Leena Haataja,5 Persistent Feature of Type 1 Asa K. Davis,3 Cate Speake,3 Linda A. DiMeglio,1,2 Janice Blum,6 Diabetes Margaret A. Morris,7 Raghavendra G. Mirmira,1,2,8,9,10 7 10,11 Diabetes Care 2019;42:258–264 | https://doi.org/10.2337/dc17-2625 Jerry Nadler, Teresa L. Mastracci, Santica Marcovina,12 Wei-Jun Qian,13 Lian Yi,13 Adam C. Swensen,13 Michele Yip-Schneider,14 C. Max Schmidt,14 Robert V. Considine,9 Peter Arvan,5 Carla J. Greenbaum,3 Carmella Evans-Molina,2,8,9,10,15 and the T1D Exchange Residual C-peptide Study Group* OBJECTIVE Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (‡3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) 1Department of Pediatrics, Indiana University ‡ 2 School of Medicine, Indianapolis, IN C-peptide positive, with high stimulated values 0.2 nmol/L; ) C-peptide posi- 2 tive, with low stimulated values ‡0.017 but <0.2 nmol/L; and 3)C-peptide Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indian- <0.017 nmol/L. -
The Saga of Antigen-Specific Immunotherapy for Type 1 Diabetes
Diabetes Volume 70, June 2021 1247 The SAgA of Antigen-Specific Immunotherapy for Type 1 Diabetes Roberto Mallone1,2 and Sylvaine You1 Diabetes 2021;70:1247–1249 | https://doi.org/10.2337/dbi21-0011 1 Islet antigen-specific strategies are the holy grail of genic BDC2.5 CD4 T cells (8), or with its more potent immunotherapy for type 1 diabetes (T1D) (1), as they se- p79 mimotope. Contrary to free peptides, these SAgAs ef- lectively target the autoimmune responses involved in ficiently prevented diabetes in NOD mice only when used b-cell destruction (2). The idea is to induce a response op- in combination. While this may reflect the need to posite to that of a conventional vaccine. The administra- achieve a critical quantitative threshold of T cells targeted, tion of antigen(s) in the absence of inflammation (e.g., a synergistic functional effect is plausible. Indeed, 2.5HIP- adjuvants) should potentiate the outcomes of physiological reactive and p79-reactive T cells, which were, surprisingly, immune homeostasis, i.e., anergy, regulatory polarization, distinct populations, underwent different outcomes upon 1 and, to a lesser extent, deletion. Such antigens can be de- treatment with their cognate SAgA (Fig. 1). IL-10 Treg- livered as proteins, peptides, bacteria engineered to secrete ulatory (Tr)1 cells were induced by the more potent p79 1 these products, DNA plasmids, or nanoparticles coated ligand, while Foxp3 Tregs were amplified, but not de with antigens (either alone or preloaded on MHC mole- novo induced, by the weaker (and less soluble) 2.5HIP. COMMENTARY cules). Peptides are easy to synthesize by amino acid These effects were dose-dependent, as SAgAs induced Tr1 1 chemistry, but they are variably water-soluble and short- cells at higher dose and Foxp3 Tregs at lower dose. -
Difficult-To-Diagnose Diabetes in a Patient Treated With
García-Sáenz et al. Journal of Medical Case Reports (2018) 12:364 https://doi.org/10.1186/s13256-018-1925-3 CASE REPORT Open Access Difficult-to-diagnose diabetes in a patient treated with cyclophosphamide – the contradictory roles of immunosuppressant agents: a case report Manuel García-Sáenz1, Daniel Uribe-Cortés1, Claudia Ramírez-Rentería2 and Aldo Ferreira-Hermosillo2* Abstract Background: Cyclophosphamide may induce autoimmune diabetes through a decrease in suppressor T cells and increase of proinflammatory T helper type 1 response in animal models. In humans, this association is not as clear due to the presence of other risk factors for hyperglycemia, but it could be a precipitant for acute complications. Case presentation: A 31-year-old Mestizo-Mexican woman with a history of systemic lupus erythematosus presented with severe diabetic ketoacidosis, shortly after initiating a multi-drug immunosuppressive therapy. She did not meet the diagnostic criteria for type 1 or type 2 diabetes and had no family history of hyperglycemic states. She persisted with hyperglycemia and high insulin requirements until the discontinuation of cyclophosphamide. After this episode, she recovered her endogenous insulin production and the antidiabetic agents were successfully withdrawn. After 1 year of follow up she is still normoglycemic. Conclusion: Cyclophosphamide may be an additional risk factor for acute hyperglycemic crisis. Glucose monitoring could be recommended during and after this treatment. Keywords: Cyclophosphamide, Diabetic ketoacidosis, Lupus erythematosus, systemic Background effect of counterregulatory hormones, diabetic ketoacidosis Most patients with diabetes mellitus (DM) are classified (DKA) may occur [3]. into the commonly accepted groups: type 1 DM (T1DM), Cyclophosphamide (CY) is a cytotoxic chemotherapeutic type 2 DM, gestational DM, latent autoimmune diabetes of agent used in the treatment of hematological diseases. -
Low Blood Glucose (Hypoglycemia)
Low Blood Glucose (Hypoglycemia) Hypoglycemia, also known as low blood Hunger, nausea glucose (blood sugar), is when your blood Color draining from skin (pallor) glucose levels have fallen low enough that you need to take action to bring them back Feeling sleepy to your target range. This is usually when your blood glucose is less than 70 mg/dL. However, Feeling weak, having no energy talk to your doctor about your own blood Blurred/impaired vision glucose targets, and what level is too low for you. Tingling or numbness in lips, tongue, cheeks Headaches When can it happen? Coordination problems, clumsiness Low blood glucose can happen if you’ve skipped a meal or snack, eaten less than usual, or been Nightmares or crying out in sleep more physically active than usual. If you don’t Seizures take steps to bring glucose levels back to normal, you could even pass out. What should you do? What are the symptoms? The 15-15 rule—have 15 grams of carbohydrate to raise your blood glucose and check it after Each person’s reaction to low blood glucose is 15 minutes. If it’s still below 70 mg/dL, have different. It’s important that you learn your own another serving. signs and symptoms when your blood glucose is low. Repeat these steps until your blood glucose is at least 70 mg/dL. Once your blood glucose is back Signs and to normal, eat a meal or snack to make sure it symptoms of doesn’t lower again. low blood glucose include: This may be: Feeling shaky Glucose tablets (see instructions) Being nervous Gel tube (see instructions) or anxious 4 ounces (1/2 cups) of juice or regular soda Sweating, chills, (not diet) clamminess 1 tablespoon of sugar, honey, or corn syrup Mood swings, irritability, impatience 8 ounces of nonfat or 1% milk Confusion Hard candies, jellybeans, or gumdrops—see Fast heartbeat food label for how many to consume Feeling light-headed or dizzy Continued » Visit diabetes.org or call 800-DIABETES (800-342-2383) for more resources from the American Diabetes Association. -
Distinct States of Proinsulin Misfolding in MIDY
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.10.442447; this version posted May 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Distinct states of proinsulin misfolding in MIDY Leena Haataja1, Anoop Arunagiri1, Anis Hassan1, Kaitlin Regan1, Billy Tsai2, Balamurugan Dhayalan3, Michael A. Weiss3, Ming Liu1,4, and Peter Arvan*1 From: 1The Division of Metabolism, Endocrinology & Diabetes and 2Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor MI 48105; 3Department of Biochemistry and Molecular Biology, Indiana University, Indianapolis, IN 46202; 4Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin 300052, China *To whom correspondence may be addressed: Peter Arvan MD PhD ORCID ID: http://orcid.org/0000-0002-4007-8799 Division of Metabolism, Endocrinology & Diabetes, University of Michigan, Brehm Tower rm 5112 1000 Wall St. Ann Arbor, MI 48105 email: [email protected] FAX: 734-232-8162 Running Title. Proinsulin Disulfide Mispairing Key Words. endoplasmic reticulum, disulfide bonds, protein trafficking, insulin, diabetes Abbreviations. ER, endoplasmic reticulum; MIDY, Mutant INS-gene induced Diabetes of Youth 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.05.10.442447; this version posted May 10, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract A precondition for efficient proinsulin export from the endoplasmic reticulum (ER) is that proinsulin meets ER quality control folding requirements, including formation of the Cys(B19)-Cys(A20) “interchain” disulfide bond, facilitating formation of the Cys(B7)-Cys(A7) bridge. -
Diabetic Ketoacidosis: Evaluation and Treatment DYANNE P
Diabetic Ketoacidosis: Evaluation and Treatment DYANNE P. WESTERBERG, DO, Cooper Medical School of Rowan University, Camden, New Jersey Diabetic ketoacidosis is characterized by a serum glucose level greater than 250 mg per dL, a pH less than 7.3, a serum bicarbonate level less than 18 mEq per L, an elevated serum ketone level, and dehydration. Insulin deficiency is the main precipitating factor. Diabetic ketoacidosis can occur in persons of all ages, with 14 percent of cases occurring in persons older than 70 years, 23 percent in persons 51 to 70 years of age, 27 percent in persons 30 to 50 years of age, and 36 percent in persons younger than 30 years. The case fatality rate is 1 to 5 percent. About one-third of all cases are in persons without a history of diabetes mellitus. Common symptoms include polyuria with polydipsia (98 percent), weight loss (81 percent), fatigue (62 percent), dyspnea (57 percent), vomiting (46 percent), preceding febrile illness (40 percent), abdominal pain (32 percent), and polyphagia (23 percent). Measurement of A1C, blood urea nitro- gen, creatinine, serum glucose, electrolytes, pH, and serum ketones; complete blood count; urinalysis; electrocar- diography; and calculation of anion gap and osmolar gap can differentiate diabetic ketoacidosis from hyperosmolar hyperglycemic state, gastroenteritis, starvation ketosis, and other metabolic syndromes, and can assist in diagnosing comorbid conditions. Appropriate treatment includes administering intravenous fluids and insulin, and monitoring glucose and electrolyte levels. Cerebral edema is a rare but severe complication that occurs predominantly in chil- dren. Physicians should recognize the signs of diabetic ketoacidosis for prompt diagnosis, and identify early symp- toms to prevent it.