diabetestalk.net

Insulin Immunity

Innate Immunity, Insulin Resistance And Type 2 Diabetes.

Innate Immunity, Insulin Resistance And Type 2 Diabetes.

Innate immunity, insulin resistance and type 2 diabetes. University Hospital of Girona Dr Josep Trueta and CIBER Fisiopatologa de la Obesidad (CB06/03/010) 17007 Girona, Spain. [email protected] Trends Endocrinol Metab. 2008 Jan;19(1):10-6. Epub 2007 Dec 21. Recent evidence has disclosed previously unrecognized links among insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to altered production or function of circulating innate immune proteins, cellular pattern-recognition receptors and inflammatory cytokines have been linked with insulin resistance, type 2 diabetes, obesity and atherosclerosis. Cellular innate immune associations with obesity and insulin resistance include increased white blood cell count and adipose tissue macrophage numbers. The innate immune response is modulated possibly by both predisposition (genetic or fetal programming), perhaps owing to evolutionary pressures caused by acute infections at the population level (pandemics), and chronic low exposure to environmental products or infectious agents. The common characteristics shared among innate immunity activation, obesity and insulin resistance are summarized. Continue reading >>

Innate Immunity, Insulin Resistance And Type 2 Diabetes

Innate Immunity, Insulin Resistance And Type 2 Diabetes

, Volume 55, Issue2 , pp 273278 | Cite as Innate immunity, insulin resistance and type 2 diabetes In this edition of Then and now the initial studies by J.C. Pickup and colleagues supporting the hypothesis that type 2 diabetes is caused by activated innate immunity, published in Diabetologia in 1997 (40:12861292), are discussed. These initial findings led to research that has uncovered links between insulin resistance, obesity, circulating immune markers, immunogenetic susceptibility, macrophage function and chronic infection. Genetic variations leading to the altered production or function of circulating innate immune proteins, cellular pattern recognition receptors and inflammatory cytokines are linked to obesity, insulin resistance and type 2 diabetes. Components of the innate immune system in the muscle, bone, liver and adipose tissue, as well as macrophages, have been revealed to play a role in systemic insulin action. Evolutionary pressures, such as acute infections at the population level (pandemics) and chronic low exposure to environmental products or infectious agents, may have contributed to increased susceptibility and to the current increase in the prevalence of insulin resistance and type 2 diabetes. Clinical studiesCytokinesGlucose toleranceInsulin resistanceInflammationInnate immunityInsulin sensitivityMacrophagesPathophysiologyType 2 diabetes Then: the origins of activated innate immunity as a factor in the pathogenesis of type 2 diabetes By the mid 1990s, many components of the pathophysiology of type 2 diabetes had been uncovered. One commonly held view was that acquired factors (such as obesity and under-activity), genetic factors, malnutrition in utero, ageing and syndrome X (now called the metabolic syndrome) result in lipolysis and increased circ Continue reading >>

Diabetes: Immune System Can Regulate Insulin

Diabetes: Immune System Can Regulate Insulin

Follow all of ScienceDaily's latest research news and top science headlines ! Diabetes: Immune system can regulate insulin Inflammation processes are responsible for the failure of insulin production in diabetes patients. The patients' own immune systems can contribute to treatment of this disease: researchers have found a feedback mechanism that could help maintain insulin production in overweight sufferers. Inflammation processes are responsible for the failure of insulin production in diabetes patients. The patients' own immune systems can contribute to treatment of this disease: researchers at the University of Basel and University Hospital Basel have found a feedback mechanism that could help maintain insulin production in overweight sufferers, as they report in the journal Immunity. In their study, the Basel-based researchers focused specifically on recently discovered ILC2 immune cells in the pancreas, where, under diabetic conditions, the protein IL33 is activated, among others. This protein stimulates the ILC2 cells, which trigger the release of insulin in overweight individuals using retinoic acid and could therefore be used to inhibit the failure of insulin production. The research conducted by scientists at the Department of Endocrinology, Diabetes and Metabolism at University Hospital Basel and the University of Basel's Department of Biomedicine gives an insight into an inflammatory network that could contribute to the maintenance of insulin production in diabetics. The complex interactions between endocrine cells and immune cells are clearly significant for the maintenance of insulin release. It is already known that obesity and diabetes lead to an excessive, pathological activation of the immune system in which the messenger substance IL1-beta plays a ce Continue reading >>

Insulin Resistance

Insulin Resistance

Tweet Insulin resistance is the name given to when cells of the body don’t respond properly to the hormone insulin. Insulin resistance is the driving factor that leads to type 2 diabetes, gestational diabetes and prediabetes. Insulin resistance is closely associated with obesity; however, it is possible to be insulin resistant without being overweight or obese. Modern research has shown that insulin resistance can be combatted by treatment methods that reduce how much insulin the body is producing or taking via insulin injections or insulin pumps. Reducing insulin resistance can be achieved by following low-carbohydrate and ketogenic diets. What is insulin resistance? The role of insulin is to allow cells of the body to take in glucose to be used as fuel or stored as body fat. [282] It also means that glucose is more likely to build up in the blood and this can lead to too high blood sugar levels. When the body becomes resistant to insulin, it tries to cope by producing more insulin. People with insulin resistance are often producing too more insulin than healthy people. Producing too much insulin is known as hyperinsulinemia. Symptoms of insulin resistance Initially, insulin resistance presents no symptoms. The symptoms only start to appear once it leads to secondary effects such as higher blood sugar levels. When this happens, the symptoms may include: Lethargy (tiredness) Hunger Difficulty concentrating (brain fog) Other signs that often appear in people with insulin resistance include: Weight gain around the middle (belly fat) High blood pressure High cholesterol levels If insulin resistance develops into prediabetes or type 2 diabetes, the symptoms will include increased blood glucose levels and more of the classic symptoms of type 2 diabetes. Causes of insulin r Continue reading >>

Can Your Body Reject Insulin If Badly Controlled?

Can Your Body Reject Insulin If Badly Controlled?

Save for later Q. Can your body reject insulin if badly controlled? A. You seem concerned that your body may be rejecting insulin that is injected which is leading to trouble controlling your blood glucose levels. If so is there a particular reason you think this may be happening? Your body does not reject injected insulin, however, if you are finding doses you are used to are not working as well or you are needing much higher doses, there could be a number of reasons for this. The first thing to check is the insulin itself. Is the insulin within the expiry date? Has it been exposed to extreme hot/cold temperatures or has it been in use for over 28 days? Any of these things could mean the insulin is damaged. If you think it may be, or you are not sure, then it might be sensible to start a new vial just to be on the safe side. Another thing to check is your injection sites/insertion sites. Are there any raised lumps, dimples or hardened areas? Any problems of this kind may interrupt the absorption rate of insulin. If you are unsure whether your injection sites are as they should be, then you may want to ask your diabetes nurse to have a look at them for you. Another thing that can happen, particularly during adolescence when hormones can be unpredictable, is that insulin resistance can develop. Insulin resistance means that any insulin you have injected cannot be used properly and so is not effective enough at lowering blood glucose levels. There can be few ways of tackling this. Insulin resistance can develop in people who are very overweight, I am not sure if this is the case for you, but losing extra weight, if applicable, should reduce insulin resistance. As mentioned before however, insulin resistance is more likely to occur during the teenage years and be completel Continue reading >>

Adaptive Immunity In Obesity And Insulin Resistance

Adaptive Immunity In Obesity And Insulin Resistance

Adaptive immunity in obesity and insulin resistance Henrike Sell was trained in obesity and diabetes research in Germany and Canada and received a PhD from Heinrich-Heine-University Dsseldorf in 2007. She is currently vice group leader at the German Diabetes-Center in Dsseldorf. Dr. Sell's research focuses on the role of adipokines in the crosstalk between adipose tissue and other organs. Jrgen Eckel is professor of Clinical Biochemistry and Head of the Paul-Langerhans-Group Integrative Physiology at the German Diabetes-Center. His main research interests include adipokines and myokines in interorgan crosstalk in the context of obesity-associated metabolic diseases and with a focus on insulin resistance in skeletal muscle in type 2 diabetes mellitus. Nature Reviews Endocrinology volume 8, pages 709716 (2012) | Download Citation Obesity is the hallmark of the metabolic syndrome and predisposes patients to the development of major chronic metabolic diseases including type 2 diabetes mellitus. Adipose tissue expansion in obesity is characterized by increasing infiltration of proinflammatory immune cells into adipose tissue causing chronic, low-grade inflammation. Phenotypic switching of macrophages is an important mechanism of adipose tissue inflammation, and there is involvement of cells from the adaptive immune system in this process. T-cell phenotype changes and recruitment of B cells and T cells precedes macrophage infiltration. Cytokines and chemokines produced by immune cells influence localized and systemic inflammation, which is a pathogenic link between obesity and insulin resistance. Antigens absorbed from the gut might contribute to T-cell activation and recruitment into visceral adipose tissue in obesity. This Review summarizes, in the context of obesity, the Continue reading >>

The Role Of The Immune System In The Insulin Resistance Syndrome

The Role Of The Immune System In The Insulin Resistance Syndrome

The role of the immune system in the insulin resistance syndrome The complex relationship between immunity and the insulin resistance syndrome is likely mediated to a significant degree by cytokines and the inflammatory proteins they induce. Epidemiologic work has revealed associations between cytokines and clinically evident insulin resistance, and mechanistic studies have yielded insight into the induction of insulin resistance at the cellular level by cytokines such as tumor necrosis factor-. Genetic polymorphisms significantly influence this relationship, and variations in cellular immunity as manifested by T-helper cell phenotype are likely to be important as well. Further elucidation of the link between immunity and insulin resistance may lead to more effective treatment, and potentially prevention, of the insulin resistance syndrome. Insulin ResistanceInsulin Resistance SyndromeDRB1 AlleleDecrease Insulin ResistanceTumor Necrosis Factor Alpha Gene These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves. This is a preview of subscription content, log in to check access. Unable to display preview. Download preview PDF. Ross R: Atherosclerosisan inflammatory disease. N Engl J Med 1999, 340:115126. PubMed CrossRef Google Scholar Pickup JC, Crook MA: Is type 2 diabetes mellitus a disease of the innate immune system? Diabetologia 1998, 41: 12411248. Effectively summarizes much of the data relating immunity to insulin resistance and presents a model linking long-term activation of the acute phase response and type 2 diabetes. PubMed CrossRef Google Scholar Zimmet P, Turner R, McCarty D, et al.: Crucial points at diagnosis. Type 2 diabetes or slow type 1 diabetes. Diabet Continue reading >>

The Effects And Mechanisms Of Insulin On Systemic Inflammatory Response And Immune Cells In Severe Trauma, Burn Injury, And Sepsis - Sciencedirect

The Effects And Mechanisms Of Insulin On Systemic Inflammatory Response And Immune Cells In Severe Trauma, Burn Injury, And Sepsis - Sciencedirect

Volume 9, Issue 11 , October 2009, Pages 1251-1259 The effects and mechanisms of insulin on systemic inflammatory response and immune cells in severe trauma, burn injury, and sepsis Author links open overlay panel Hu-pingDeng Jia-keChai Get rights and content Insulin resistance, hyperglycemia, inflammatory disorders and immune dysfunction cause high morbidity and mortality in patients with severe trauma, burn injuries, or sepsis. Many studies have shown that intensive insulin therapy can combat insulin resistance, decrease blood glucose levels, and induce anabolic processes, thus, decreasing morbidity and mortality. Moreover, in recent years, it has been proven that insulin can attenuate systemic inflammatory responses and modulate the proliferation, apoptosis, differentiation and immune functions of certain immune cells, especially monocytes/macrophages, neutrophils, and T cells associated with severe trauma, burn injury, or sepsis. This effect of insulin may expand our understanding of intensive insulin therapy in critically ill patients. This review attempts to summarize studies on the modulatory effects and mechanisms of insulin therapy on systemic inflammation and immune cells in severe trauma, burn injury and sepsis, and further propose some questions for future studies. Continue reading >>

Insulin Treatment Modulates The Host Immune System To Enhance Pseudomonas Aeruginosa Wound Biofilms

Insulin Treatment Modulates The Host Immune System To Enhance Pseudomonas Aeruginosa Wound Biofilms

ABSTRACT Diabetes affects 25.8 million people in the United States, or 8.3% of the population, and these numbers are even higher in developing countries. Diabetic patients are more susceptible to the development of chronic wounds with debilitating bacterial infections than nondiabetics. Previously, we compared the ability of the opportunistic pathogen Pseudomonas aeruginosa to cause biofilm-associated infections in chronic wounds of diabetic and nondiabetic mice (C. Watters, K. DeLeon, U. Trivedi, J. A. Griswold, M. Lyte, K. J. Hampel, M. J. Wargo, and K. P. Rumbaugh, Med. Microbiol. Immunol. 202:131–141, 2013). Unexpectedly, we observed that insulin-treated diabetic mice had significantly more biofilm in their wounds, which correlated with higher antibiotic tolerance. Here, we investigated whether insulin treatment modulates the diabetic immune system to favor P. aeruginosa biofilm formation. Utilizing a murine chronic wound model, we found that DNA protected P. aeruginosa in the wounds of insulin-treated diabetic mice from antibiotic treatment. We also observed increased numbers of neutrophils, reduced numbers of macrophages, and increased cell death in the wounds of diabetic mice on insulin therapy. Taken together, these data suggest that high levels of lysed neutrophils in the wounds of diabetic mice on insulin, combined with fewer macrophages to remove the cellular debris, contribute to increased DNA levels, which enhance P. aeruginosa biofilms. Continue reading >>

Insulin Resistance

Insulin Resistance

What medical conditions are associated with insulin resistance? While the metabolic syndrome links insulin resistance with abdominal obesity, elevated cholesterol, and high blood pressure; several other medical other conditions are specifically associated with insulin resistance. Insulin resistance may contribute to the following conditions: Type 2 Diabetes: Overt diabetes may be the first sign insulin resistance is present. Insulin resistance can be noted long before type 2 diabetes develops. Individuals reluctant or unable to see a health-care professional often seek medical attention when they have already developed type 2 diabetes and insulin resistance. Fatty liver: Fatty liver is strongly associated with insulin resistance. Accumulation of fat in the liver is a manifestation of the disordered control of lipids that occurs with insulin resistance. Fatty liver associated with insulin resistance may be mild or severe. Newer evidence suggests fatty liver may even lead to cirrhosis of the liver and, possibly, liver cancer. Arteriosclerosis: Arteriosclerosis (also known as atherosclerosis) is a process of progressive thickening and hardening of the walls of medium-sized and large arteries. Arteriosclerosis is responsible for: Other risk factors for arteriosclerosis include: High levels of "bad" (LDL) cholesterol Diabetes mellitus from any cause Family history of arteriosclerosis Skin Lesions: Skin lesions include increased skin tags and a condition called acanthosis nigerians (AN). Acanthosis nigricans is a darkening and thickening of the skin, especially in folds such as the neck, under the arms, and in the groin. This condition is directly related to the insulin resistance, though the exact mechanism is not clear. Acanthosis nigricans is a cosmetic condition strongly Continue reading >>

New Role For Insulin: Affects Immune System As Well As Metabolism

New Role For Insulin: Affects Immune System As Well As Metabolism

Researchers have found a previously unknown link between metabolism and immunity, discovering more about why chronic inflammation develops in people who have obesity. In new research, Dr. Megan Levings and colleagues demonstrate that insulin can damage regulatory immune cells, causing more inflammation in fat tissue. Cells in people who have obesity often respond poorly to insulin, causing poor regulation of blood sugar. The body attempts to compensate by making more insulin, but over time unregulated blood sugar puts people at risk for complications such as type 2 diabetes, hypertension, cardiovascular disease and even some types of cancer later in life. The condition is especially worrisome in children who have obesity, as they face increased life-time risk of these complications. In this study, the researchers looked at mice that were obese and found that high levels of insulin prevent a type of immune cell called regulatory T cells – or Tregs – from doing their job to suppress inflammation. This finding could lead to new treatments for obesity-related complications, such as therapies for repairing Tregs. As a next step, the researchers are studying blood and adipose fat tissue donated from adults undergoing bariatric surgery. The research is published in the January 2014 print issue of The Journal of Immunology. The journal is featuring the findings in a special section called “In This Issue”, which highlights articles considered to be among the top 10 per cent of articles published in that issue. “This work represents a new and exciting collaboration between me and my colleague Dr. Jan Ehses in the whole new area of immunometabolism,” says Dr. Megan Levings, study’s lead investigator. Dr. Levings is a scientist at the Child & Family Research Institute Continue reading >>

A Complex Relationship Between Immunity And Metabolism In Drosophila Diet-induced Insulin Resistance

A Complex Relationship Between Immunity And Metabolism In Drosophila Diet-induced Insulin Resistance

A Complex Relationship between Immunity and Metabolism in Drosophila Diet-Induced Insulin Resistance aBinghamton University, Department of Biological Sciences, Binghamton, New York, USA bWashington University School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, St. Louis, Missouri, USA cBioinformatics Core, University of Michigan, Ann Arbor, Michigan, USA Both systemic insulin resistance and tissue-specific insulin resistance have been described in Drosophila and are accompanied by many indicators of metabolic disease. The downstream mediators of insulin-resistant pathophysiology remain unclear. We analyzed insulin signaling in the fat body studying loss and gain of function. When expression of the sole Drosophila insulin receptor (InR) was reduced in larval fat bodies, animals exhibited developmental delay and reduced size in a diet-dependent manner. Fat body InR knockdown also led to reduced survival on high-sugar diets. To look downstream of InR at potential mediators of insulin resistance, transcriptome sequencing (RNA-seq) studies in insulin-resistant fat bodies revealed differential expression of genes, including those involved in innate immunity. Obesity-associated insulin resistance led to increased susceptibility of flies to infection, as in humans. Reduced innate immunity was dependent on fat body InR expression. The peptidoglycan recognition proteins (PGRPs) PGRP-SB2 and PGRP-SC2 were selected for further study based on differential expression studies. Downregulating PGRP-SB2 selectively in the fat body protected animals from the deleterious effects of overnutrition, whereas downregulating PGRP-SC2 produced InR-like phenotypes. These studies extend earlier work linking the immune and insulin signaling pathway Continue reading >>

The Role Of The Immune System In Obesity And Insulin Resistance

The Role Of The Immune System In Obesity And Insulin Resistance

Journal of Obesity Volume 2013 (2013), Article ID 616193, 9 pages 1Diabetes Research Center, Division of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX 77030, USA 2Endocrine Service, Ben Taub General Hospital, Houston, TX 77030, USA Academic Editor: Nicola Abate Copyright © 2013 Payal S. Patel 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. Abstract The innate immune system provides organisms with rapid and well-coordinated protection from foreign pathogens. However, under certain conditions of metabolic dysfunction, components of the innate immune system may be activated in the absence of external pathogens, leading to pathologic consequences. Indeed, there appears to be an intimate relationship between metabolic diseases and immune dysfunction; for example, macrophages are prime players in the initiation of a chronic inflammatory state in obesity which leads to insulin resistance. In response to increases in free fatty acid release from obese adipose depots, M1-polarized macrophages infiltrate adipose tissues. These M1 macrophages trigger inflammatory signaling and stress responses within cells that signal through JNK or IKKβ pathways, leading to insulin resistance. If overnutrition persists, mechanisms that counteract inflammation (such as M2 macrophages and PPAR signaling) are suppressed, and the inflammation becomes chronic. Although macrophages are a principal constituent of obese adipose tissue inflammation, other components of the immune system such as lymphocytes and mast cells also contribute to the inflammatory cascade. Thus it is not merely an increa Continue reading >>

Role Of Insulin In Immunity!!

Role Of Insulin In Immunity!!

It has been well known for decades already, that immune cells also have insulin receptors, which to me turns out most obvious, as "these cells need to eat as well as anyother". They certainly need to incorporate and use glucose for their normal methabolism, so any alteration of Glucose / Insulin balance can affect their functioning as it does with the rest of the somatic and visceral cells. In fact, steroids for instance, influence this balance and in part, I think they should be held responsable for their effect on celular immune regulation. It is obvious that on systemic basis analysis, the physiological status of a severely uncompensated diabetic patient with hiperinsulinemia in response to hyperglycemia, hyperosmolarity, dehydration and keto-acidosis, affects all homeostatic balance including that of lymphoreticular and bone marrow organs and systems. Old in vitro experiments have approached "the nutritional and methabolic needs of lymphoyd and mononuclear cells". Continue reading >>

Nod1 Activators Link Innate Immunity To Insulin Resistance

Nod1 Activators Link Innate Immunity To Insulin Resistance

NOD1 Activators Link Innate Immunity to Insulin Resistance 1Program in Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada 2Department of Medicine, McMaster University, Hamilton, Ontario, Canada 3Department of Immunology, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada 4Department of Physiology, Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada Corresponding author: Amira Klip, amira{at}sickkids.ca. Diabetes 2011 Sep; 60(9): 2206-2215. OBJECTIVE Insulin resistance associates with chronic inflammation, and participatory elements of the immune system are emerging. We hypothesized that bacterial elements acting on distinct intracellular pattern recognition receptors of the innate immune system, such as bacterial peptidoglycan (PGN) acting on nucleotide oligomerization domain (NOD) proteins, contribute to insulin resistance. RESEARCH DESIGN AND METHODS Metabolic and inflammatory properties were assessed in wild-type (WT) and NOD1/2/ double knockout mice fed a high-fat diet (HFD) for 16 weeks. Insulin resistance was measured by hyperinsulinemic euglycemic clamps in mice injected with mimetics of meso-diaminopimelic acidcontaining PGN or the minimal bioactive PGN motif, which activate NOD1 and NOD2, respectively. Systemic and tissue-specific inflammation was assessed using enzyme-linked immunosorbent assays in NOD ligandinjected mice. Cytokine secretion, glucose uptake, and insulin signaling were assessed in adipocytes and primary hepatocytes exposed to NOD ligands in vitro. RESULTS NOD1/2/ mice were protected from HFD-induced inflammation, lipid accumulation, and peripheral insulin intolerance. Conversely, direct activation of NOD1 protein caused insulin resistance. NOD1 ligands induced peripheral Continue reading >>

More in insulin