Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes

Larsen, Claus M.; Faulenbach, Mirjam; Vaag, Allan; Ehses, Jan A.; Donath, Marc Y.; Mandrup-Poulsen, Thomas

doi:10.2337/dc09-0533

Cited by 352 publications

(298 citation statements)

References 26 publications

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“…Whether inflammation is also present in islets and whether this contributes to the development of type 2 diabetes are important questions because of the central role of beta cell dysfunction in the disease pathogenesis [22]. Moreover, IL-1ra therapy is under evaluation for the treatment of type 2 diabetes [34,35], based on studies suggesting that high-glucose-induced IL-1β secretion by beta cells causes beta cell dysfunction and death [21].…”

Section: Discussionmentioning

confidence: 99%

Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes

et al. 2010

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Aims/hypothesis Beta cell failure is a crucial component in the pathogenesis of type 2 diabetes. One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate.Methods Chemokine and cytokine expression was studied by microarray analysis of laser-capture microdissected islets from pancreases obtained from ten non-diabetic and ten type 2 diabetic donors, and by real-time PCR of human islets exposed to oleate or palmitate at 6 or 28 mmol/l glucose. The cellular source of the chemokines was analysed by immunofluorescence of pancreatic sections from individuals without diabetes and with type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes

et al. 2010

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“…The effects on beta cell function and inflammatory markers were sustained after 39 weeks [85]. Interestingly, the baseline endogenous circulating IL-1RA level was markedly lower in patients responding to IL-1RA therapy, and this difference was stable at 52 weeks of followup.…”

Section: Lessons From Immune Intervention Trialsmentioning

confidence: 93%

The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation

Kolb¹,

2009

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The recent major increase in the global incidence of type 2 diabetes suggests that most cases of this disease are caused by changes in environment and lifestyle. All major risk factors for type 2 diabetes (overnutrition, low dietary fibre, sedentary lifestyle, sleep deprivation and depression) have been found to induce local or systemic low-grade inflammation that is usually transient or milder in individuals not at risk for type 2 diabetes. By contrast, inflammatory responses to lifestyle factors are more pronounced and prolonged in individuals at risk of type 2 diabetes and appear to occur also in the pancreatic islets. Chronic low-grade inflammation will eventually lead to overt diabetes if counter-regulatory circuits to inflammation and metabolic stress are compromised because of a genetic and/or epigenetic predisposition. Hence, it is not the lifestyle change per se but a deficient counter-regulatory response in predisposed individuals which is crucial to disease pathogenesis. Novel approaches of intervention may target these deficient defence mechanisms.

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“…Moreover, two studies have demonstrated persistent effects up to several weeks after treatment cessation with anakinra [71] or anti-IL-1β antibody [70]. Although the short duration of these studies does not provide definitive conclusions, data suggests that IL-1β blocking activity enhances glucose control in diabetic patients by improving the β-cell function and may even allow a partial generation these cells.…”

Section: Anti-il-1βmentioning

confidence: 99%

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

Esser

Legrand-Poels

Piette

et al. 2014

Diabetes Research and Clinical Practice

1,525

1,064

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:It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes.

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Sustained Effects of Interleukin-1 Receptor Antagonist Treatment in Type 2 Diabetes

Cited by 352 publications

References 26 publications

Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes

Palmitate induces a pro-inflammatory response in human pancreatic islets that mimics CCL2 expression by beta cells in type 2 diabetes

The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation

Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes

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