Evidence against a role for NLRP3-driven islet inflammation in db/db mice.

Molecular Metabolism
H L KammounM A Febbraio

Abstract

Type 2 diabetes (T2D) is associated with chronic, low grade inflammation. Activation of the NLRP3 inflammasome and secretion of its target interleukin-1β (IL-1β) have been implicated in pancreatic β cell failure in T2D. Specific targeting of the NLRP3 inflammasome to prevent pancreatic β cell death could allow for selective T2D treatment without compromising all IL-1β-associated immune responses. We hypothesized that treating a mouse model of T2D with MCC950, a compound that specifically inhibits NLRP3, would prevent pancreatic β cell death, thereby preventing the onset of T2D. Diabetic db/db mice were treated with MCC950 via drinking water for 8 weeks from 6 to 14 weeks of age, a period over which they developed pancreatic β cell failure. We assessed metabolic parameters such as body composition, glucose tolerance, or insulin secretion over the course of the intervention. MCC950 was a potent inhibitor of NLRP3-induced IL-1β in vitro and was detected at high levels in the plasma of treated db/db mice. Treatment of pre-diabetic db/db mice with MCC950, however, did not prevent pancreatic dysfunction and full onset of the T2D pathology. When examining the NLRP3 pathway in the pancreas of db/db mice, we could not detect an activati...Continue Reading

Citations

Oct 27, 2018·International Journal of Molecular Sciences·James S LeeKiarash Khosrotehrani
May 16, 2019·Nature Chemical Biology·Rebecca C CollKate Schroder
Sep 21, 2018·Frontiers in Molecular Neuroscience·Bo-Zong ShaoChong Liu
Oct 19, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Haroon KhanEsra Kupeli Akkol
Jul 22, 2021·Nature Reviews. Immunology·Andrew J Murphy, Mark A Febbraio
Sep 21, 2021·Phytotherapy Research : PTR·Seyyed Hossein HasheminezhadMilad Iranshahy
Jan 15, 2022·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Changjiang YingXiaoyan Zhou

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BETA
ELISA
PCR

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Sigma Stat

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