Sa1544: DIABETIC HYPERGLYCEMIA EXACERBATES INFLAMMATORY BOWEL DISEASE IN MICE WITH DIET-INDUCED OBESITY

Francis, Kendra; Pacheco, M.C.; Alonge, Kimberly M.; Phan, Bao Anh; Hu, Shannon; Doan, Tammy; Schwartz, Michael; Scarlett, Jarrad

doi:10.1016/s0016-5085(22)60971-5

Cited by 1 publication

(1 citation statement)

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“…Whilst we did not examine gut barrier integrity in this study, interestingly, similar to IL-22ra1 −/− animals 15 , no changes in systemic inflammation were noted in the IL-22ra1 ΔβKO mice. However, it is important to note that most studies examining gut barrier integrity during impaired glucose metabolism involve obesity or other forms of systemic metabolic stress 29,40,41 . We show that IL-22ra1 ΔβKO mice had impaired glucose tolerance even in the absence of insulin resistance and obesity.…”

Section: Discussionmentioning

confidence: 99%

Pancreatic beta-cell IL-22 receptor deficiency induces age-dependent dysregulation of insulin biosynthesis and systemic glucose homeostasis

Sajiir,

Wong,

Müller

et al. 2024

Nat Commun

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The IL-22RA1 receptor is highly expressed in the pancreas, and exogenous IL-22 has been shown to reduce endoplasmic reticulum and oxidative stress in human pancreatic islets and promote secretion of high-quality insulin from beta-cells. However, the endogenous role of IL-22RA1 signaling on these cells remains unclear. Here, we show that antibody neutralisation of IL-22RA1 in cultured human islets leads to impaired insulin quality and increased cellular stress. Through the generation of mice lacking IL-22ra1 specifically on pancreatic alpha- or beta-cells, we demonstrate that ablation of murine beta-cell IL-22ra1 leads to similar decreases in insulin secretion, quality and islet regeneration, whilst increasing islet cellular stress, inflammation and MHC II expression. These changes in insulin secretion led to impaired glucose tolerance, a finding more pronounced in female animals compared to males. Our findings attribute a regulatory role for endogenous pancreatic beta-cell IL-22ra1 in insulin secretion, islet regeneration, inflammation/cellular stress and appropriate systemic metabolic regulation.

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