Donath MY, Shoelson SEType 2 diabetes as an inflammatory disease. Nat Rev Immunol 11(2): 98-107

ArticleinNature Reviews Immunology 11(2):98-107 · February 2011with155 Reads
DOI: 10.1038/nri2925 · Source: PubMed
Components of the immune system are altered in obesity and type 2 diabetes (T2D), with the most apparent changes occurring in adipose tissue, the liver, pancreatic islets, the vasculature and circulating leukocytes. These immunological changes include altered levels of specific cytokines and chemokines, changes in the number and activation state of various leukocyte populations and increased apoptosis and tissue fibrosis. Together, these changes suggest that inflammation participates in the pathogenesis of T2D. Preliminary results from clinical trials with salicylates and interleukin-1 antagonists support this notion and have opened the door for immunomodulatory strategies for the treatment of T2D that simultaneously lower blood glucose levels and potentially reduce the severity and prevalence of the associated complications of this disease.
    • "Sedentary lifestyles combined with high-energy diets have led to an unprecedented prevalence of obesity and obesityrelated disorders. Type 2 diabetes (T2D) is a chronic inflammatory disease induced by obesity (Donath and Shoelson, 2011 ). Prominent features of T2D include low-grade chronic inflammation, hyperglycemia, hyperlipidemia and pancreatic -cell dysfunction. "
    [Show abstract] [Hide abstract] ABSTRACT: The alarming rise of obesity and type 2 diabetes (T2D) has put a tremendous strain on global healthcare systems. Over the past decade extensive research has focused on the role of macrophages as key mediators of inflammation in T2D. The inflammatory environment in the obese adipose tissue and pancreatic β-cell islets creates and perpetuates imbalanced inflammatory macrophage activation. Consequences of this chronic low-grade inflammation include insulin resistance in the adipose tissue and pancreatic β-cell dysfunction. Recently, the emerging field of epigenetics has provided new insights into the pathogenesis of T2D, while also affording potential new opportunities for treatment. In macrophages, epigenetic mechanisms are increasingly being recognized as crucial controllers of their phenotype. Here, we first describe the role of macrophages in T2D. Then we elaborate on epigenetic mechanisms that regulate macrophage activation, thereby focusing on T2D. Next, we highlight how diabetic conditions such as hyperlipidemia and hyperglycemia could induce epigenetic changes that promote an inflammatory macrophage phenotype. In conclusion we discuss possible therapeutic interventions by targeting macrophage epigenetics and speculate on future research directions.
    Full-text · Article · Sep 2016
    • "The immunological changes include varied levels of specific cytokines and chemokins as well as increased apoptosis and tissue fibrosis. These changes, when combined, suggest that inflammation plays an important role in the pathogenesis of DM (Donath & Shoelson, 2011). In the past few years, there has been an exponential growth in the field of herbal medicine because of their natural origin and reduced side effects. "
    [Show abstract] [Hide abstract] ABSTRACT: Diabetes mellitus (DM) remains a major health care problem worldwide both in developing and developed countries. Many factors, including age, obesity, sex, and diet, are involved in the etiology of DM. Nowadays, drug and dietetic therapies are the two major approaches used for prevention and control of DM. Compared to drug therapy, a resurgence of interest in using diet to manage and treat DM has emerged in recent years. Conventional dietary methods to treat DM include the use of culinary herbs and/or spices. Spices have long been known for their antioxidant, anti-inflammatory, and anti-diabetic properties. This review explores the anti-diabetic properties of commonly used spices, such as cinnamon, ginger, turmeric, and cumin, and the use of these spices for prevention and management of diabetes and associated complications.
    Full-text · Article · Aug 2016
    • "T2D is a leading cause of morbidity and mortality worldwide, and increasing evidence suggests that chronic inflammation is one of the important pathogenic factors in the development of insulin resistance and T2D (Donath and Shoelson, 2011 ). The NLRP3 inflammasome is implicated in the development of insulin resistance in T2D (Masters et al., 2010; Vandanmagsar et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Ethnopharmacological relevance: Juniperus rigida Sieb. (J. rigida) is used for medicinal purposes in Asian countries to treat inflammation-related disorders, such as neuralgia, dropsy, and gout. Aim of the study: The anti-inflammatory effects of J. rigida extract (JR) and its underlying mechanisms were explored both in in vitro cell lines and in vivo metabolic disease models. Material and methods: Lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were used to study the changes in inflammatory responses in vitro. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of JR on inflammasome activation. The murine model for monosodium urate (MSU)-induced peritonitis and high-fat diet (HFD)-induced type 2 diabetes were employed to study the effect of JR on in vivo efficacy. Results: JR suppressed the MSU-induced in vivo inflammatory response by attenuation of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). In the in vitro study, JR suppressed IL-1β secretion via regulation of apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of inflammasome activation. JR also inhibited the LPS-stimulated release of proinflammatory mediators, such as nitric oxide (NO), TNF-α, and IL-6 in RAW264.7 cells. The inhibitory effects of JR were mediated through the regulation of the TRIF-dependent signaling pathway from JAK1/STAT1 phosphorylation. Furthermore, JR showed inhibitory effects on HFD-induced type 2 diabetes in a mouse model through the regulation of blood glucose and serum IL-1β. Conclusions: Our results indicate that JR attenuates both LPS-stimulated and danger-signal-induced inflammatory responses in macrophages via regulation of the key inflammatory mechanisms, providing scientific support for its traditional use in the treatment of various inflammation-related metabolic disorders.
    Full-text · Article · May 2016
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