The IL-1<i>β</i>Receptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice

Cucak, Helena; Hansen, Gitte; Vrang, Niels; Skarsfeldt, Torben; Steiness, Eva; Jelsing, Jacob

doi:10.1155/2016/7484601

Cited by 6 publications

(5 citation statements)

References 38 publications

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“…Considering the role of proinflammatory cytokines on the pathogenesis of diabetes, population with detectable levels of circulating IL-1β cytokines have increased risk to develop diabetes ( 28 – 30 ). We speculate that sodium butyrate could relieve diabetes reflected by decreased level of IL-1β.…”

Section: Resultsmentioning

confidence: 99%

Sodium Butyrate Ameliorates Streptozotocin-Induced Type 1 Diabetes in Mice by Inhibiting the HMGB1 Expression

et al. 2018

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Type 1 diabetes (T1D) is an autoimmune disease characterized by the immune cell-mediated progressive destruction of pancreatic β-cells. High-mobility group box 1 protein (HMGB1) has been recognized as a potential immune mediator to enhance the development of T1D. So we speculated that HMGB1 inhibitors could have anti-diabetic effect. Sodium butyrate is a short fatty acid derivative possessing anti-inflammatory activity by inhibiting HMGB1. In the current study, we evaluated the effects of sodium butyrate in streptozotocin (STZ)-induced T1D mice model. Diabetes was induced by multiple low-dose injections of STZ (40 mg/kg/day for 5 consecutive days), and then sodium butyrate (500 mg/kg/day) was administered by intraperitoneal injection for 7 consecutive days after STZ treatment. Blood glucose, incidence of diabetes, body weight, pancreatic histopathology, the amounts of CD4+T cell subsets, IL-1β level in serum and pancreatic expressions levels of HMGB1, and NF-κB p65 protein were analyzed. The results showed that sodium butyrate treatment decreased blood glucose and serum IL-1β, improved the islet morphology and decreased inflammatory cell infiltration, restored the unbalanced Th1/Th2 ratio, and down-regulated Th17 to normal level. In addition, sodium butyrate treatment can inhibit the pancreatic HMGB1 and NF-κB p65 protein expression. Therefore, we proposed that sodium butyrate should ameliorate STZ-induced T1D by down-regulating NF-κB mediated inflammatory signal pathway through inhibiting HMGB1.

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Section: Resultsmentioning

confidence: 99%

Sodium Butyrate Ameliorates Streptozotocin-Induced Type 1 Diabetes in Mice by Inhibiting the HMGB1 Expression

et al. 2018

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“…A significant improvement in the first-phase insulin secretion and pancreatic β-cell function was found (325) (Table II). In line with these findings, cucak et al (326) evaluated in female non-obese diabetic (nod) mice, the effects of Ser140, which is a 10-amino-acid peptide antagonist of il-1β receptors (il-1ra), on the progression of diabetes and pancreatic β-cell changes. The study consisted of an 8-week treatment period.…”

Section: Therapeutic Interventions On Inflammatory Mediators For the ...mentioning

confidence: 95%

“…Additionally, SER140 administration changed the immune-endocrine dynamics in the NOD mouse pancreas. The authors suggested that the SER140 treatment can postpone the onset of diabetes in female NOD mice by competing with IL-1β for IL-1β receptors (IL-1R) ( 326 ).…”

Section: Therapeutic Interventions On Inflammatory Mediators For the ...mentioning

confidence: 99%

Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review)

Varra,

Varras,

Varra

et al. 2024

Mol Med Rep

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Obesity reaches up to epidemic proportions globally and increases the risk for a wide spectrum of co-morbidities, including type-2 diabetes mellitus (T2DM), hypertension, dyslipidemia, cardiovascular diseases, non-alcoholic fatty liver disease, kidney diseases, respiratory disorders, sleep apnea, musculoskeletal disorders and osteoarthritis, subfertility, psychosocial problems and certain types of cancers. The underlying inflammatory mechanisms interconnecting obesity with metabolic dysfunction are not completely understood. Increased adiposity promotes pro-inflammatory polarization of macrophages toward the M1 phenotype, in adipose tissue (AT), with subsequent increased production of pro-inflammatory cytokines and adipokines, inducing therefore an overall, systemic, low-grade inflammation, which contributes to metabolic syndrome (MetS), insulin resistance (IR) and T2DM. Targeting inflammatory mediators could be alternative therapies to treat obesity, but their safety and efficacy remains to be studied further and confirmed in future clinical trials. The present review highlights the molecular and pathophysiological mechanisms by which the chronic low-grade inflammation in AT and the production of reactive oxygen species lead to MetS, IR and T2DM. In addition, focus is given on the role of anti-inflammatory agents, in the resolution of chronic inflammation, through the blockade of chemotactic factors, such as monocytes chemotractant protein-1, and/or the blockade of pro-inflammatory mediators, such as IL-1β, ΤΝF-α, visfatin, and plasminogen activator inhibitor-1, and/or the increased synthesis of adipokines, such as adiponectin and apelin, in obesity-associated metabolic dysfunction.

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“…When administered to diabetic KK‐A y mice, the formulation was able to enhance glucose tolerance, insulin sensitivity while decrease free fatty acids in serum, cholesterol, β‐cell death, and IL‐1β production. Likewise, a different peptide antagonist of IL‐1β, SER140, was found to preserve β‐cell mass and delay the diabetes development in NOD mice …”

Section: Cytokines and Therapies That Modulate Their Activitymentioning

confidence: 99%

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies

Banerjee

Singh

2019

Bioengineering & Transla Med

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Obesity-associated type 2 diabetes mellitus (T2DM) is characterized by low-grade chronic systemic inflammation that arises primarily from the white adipose tissue. The interplay between various adipose tissue-derived chemokines drives insulin resistance in T2DM and has therefore become a subject of rigorous investigation. The adipocytokines strongly associated with glucose homeostasis include tumor necrosis factor-α, various interleukins, monocyte chemoattractant protein-1, adiponectin, and leptin, among others. Remodeling the adipose tissue inflammasome in obesity-associated T2DM is likely to treat the underlying cause of the disease and bring significant therapeutic benefit. Various strategies have been adopted or are being investigated to modulate the serum/tissue levels of pro-and anti-inflammatory adipocytokines to improve glucose homeostasis in T2DM. These include use of small molecule agonists/inhibitors, mimetics, antibodies, gene therapy, and other novel formulations. Here, we discuss adipocytokines that are strongly associated with insulin activity and therapies that are under investigation for modulation of their levels in the treatment of T2DM.

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The IL-1βReceptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice

Cited by 6 publications

References 38 publications

Sodium Butyrate Ameliorates Streptozotocin-Induced Type 1 Diabetes in Mice by Inhibiting the HMGB1 Expression

Sodium Butyrate Ameliorates Streptozotocin-Induced Type 1 Diabetes in Mice by Inhibiting the HMGB1 Expression

Molecular and pathophysiological relationship between obesity and chronic inflammation in the manifestation of metabolic dysfunctions and their inflammation‑mediating treatment options (Review)

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies

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