The interleukin‐1 receptor antagonist anakinra improves first‐phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance

Poppel, P.C.M. van; Asseldonk, Edwin J.P. van; Holst, Jens J.; Vilsbøll, Tina; Netea, Mihai G.; Tack, Cees J.

doi:10.1111/dom.12357

Cited by 48 publications

(24 citation statements)

References 14 publications

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“…Blocking of IL‐1 by Anakinra in glucose intolerant patients improved insulin secretion compared with placebo . Similar data were obtained when Canakinumab was used in a placebo‐controlled trial .…”

Section: Obesity and Diabetes Complications Are Tightly Linked To Il‐1supporting

confidence: 65%

“…Blocking of IL-1 by Anakinra in glucose intolerant patients improved insulin secretion compared with placebo. 132 Similar data were obtained when Canakinumab was used in a placebo-controlled trial. 133 Similarly, better glycemic control and improved β cell secretory function was observed in type 2 diabetic patients treated with 100 mg Anakinra for 13 weeks compared to placebo.…”

Section: Obesity and Diabetes Complications Are Tightly Linked To Il-1supporting

confidence: 59%

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Interleukin 1 gene polymorphism and susceptibility to disease

Khazim

Azulay

Kristal

et al. 2017

Immunological Reviews

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The Interleukin 1 (IL-1) family plays a central role in the generation and regulation of inflammatory responses, in both innate and adaptive immunity. Although the IL-1 molecules are traditionally considered to be classical proinflammatory cytokines, their functions are not restricted to inflammation, and they have also been shown to play a key role in a wide range of additional physiological and pathological functions, including learning modulation, sleep, pregnancy, depression, appetite, hematopoiesis, metabolism, and many others. Since their effect as cytokines and regulators of inflammation is so pleiotropic, any shift of the biological balance between agonistic and antagonistic signals has the potential to cause disease. Here, we consider the genetic influence of interleukin-1 gene polymorphism in the context of susceptibility to human diseases. We review known single nucleotide polymorphisms (SNP) of IL-1 genes linked to human diseases, and suggest how exploring biological effects of IL-1 gene cluster polymorphism may lead to new directions in understanding and diagnostic of disease and effective treatment.

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Section: Obesity and Diabetes Complications Are Tightly Linked To Il‐1supporting

confidence: 65%

Section: Obesity and Diabetes Complications Are Tightly Linked To Il-1supporting

confidence: 59%

Interleukin 1 gene polymorphism and susceptibility to disease

Khazim

Azulay

Kristal

et al. 2017

Immunological Reviews

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“…Interestingly, clinical interventions targeting the IL-1 signaling pathway improved islet β-cell function in human subjects with impaired glucose tolerance [74, 75] and those with overt diabetes [76] but did not alleviate peripheral insulin resistance in either group. This therapeutic outcome could be explained by decreasing the availability of the ligand(s) activating IL-1RI, which is highly expressed on islet β-cells relative to other tissues [7].…”

Section: 1 Discussionmentioning

confidence: 99%

CCL20 is elevated during obesity and differentially regulated by NF-κB subunits in pancreatic β-cells

Burke

Karlstad

Regal

et al. 2015

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Enhanced leukocytic infiltration into pancreatic islets contributes to inflammation-based diminutions in functional β-cell mass. Insulitis (aka islet inflammation), which can be present in both T1DM and T2DM, is one factor influencing pancreatic β-cell death and dysfunction. IL-1β, an inflammatory mediator in both T1DM and T2DM, acutely (within 1h) induced expression of the CCL20 gene in rat and human islets and clonal β-cell lines. Transcriptional induction of CCL20 required the p65 subunit of NF-κB to replace the p50 subunit at two functional κB sites within the CCL20 proximal gene promoter. The NF-κB p50 subunit prevents CCL20 gene expression during unstimulated conditions and overexpression of p50 reduces CCL20, but enhances cyclooxygenase-2 (COX-2), transcript accumulation after exposure to IL-1β. We also identified differential recruitment of specific co-activator molecules to the CCL20 gene promoter, when compared with the CCL2 and COX2 genes, revealing distinct transcriptional requirements for individual NF-κB responsive genes. Moreover, IL-1β, TNF-α and IFN-γ individually increased the expression of CCR6, the receptor for CCL20, on the surface of human neutrophils. We further found that the chemokine CCL20 is elevated in serum from both genetically obese db/db mice and in C57BL6/J mice fed a high-fat diet. Taken together, these results are consistent with a possible activation of the CCL20-CCR6 axis in diseases with inflammatory components. Thus, interfering with this signaling pathway, either at the level of NF-κB-mediated chemokine production, or downstream receptor activation, could be a potential therapeutic target to offset inflammation-associated tissue dysfunction in obesity and diabetes.

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“…van Poppel и соавт. [46]. Несмотря на это, у детей с дебютом СД 1-го типа ни канакинумаб (n=45), ни анакинра (n=25) не влияли на концентрацию С-пептида через 12 и 9 мес терапии соответственно [47].…”

Section: анакинра и канакинумабunclassified