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Inhibition of the NLRP3 Inflammasome Prevents Hyperglycemia in a Humanized Rodent Model of Type 2 Diabetes

Meier, D.;Dalmas, E.;Rachid, L.;Guernic, A.;Baumann, Z.;Venteclef, N.;Donath, M.

2026-06-20 Cell Biology
10.64898/2026.06.19.733338 bioRxiv
Show abstract

The NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome is a protein complex that senses metabolic disturbances and in response processes IL-1beta. Prolonged activation of the NLRP3 inflammasome by metabolic stress induces chronic low-grade inflammation and contributes to the development type 2 diabetes and its comorbidities. Here, we developed a mouse model of type 2 diabetes that features impaired proinsulin processing and the ability to form islet amyloid plaques, two determinants of human type 2 diabetes pathology. We show that at advanced ages, these mice develop amyloidosis and inflammation in their insulin-producing pancreatic islets. Beta-cell mass and function were impaired in these mice and severe hyperglycemia developed within 6 months. Oral application of OLT1177, a selective inhibitor of the NLRP3 inflammasome, prevented the development of hyperglycemia. Our data show that inhibition of the NLRP3 inflammasome in a humanized mouse model of severe type 2 diabetes prevents the development of amyloid-associated hyperglycemia.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.