Supplementary Figure 7: Glucose homeostasis of Tnfaip3^I325N mice and isolated islets.

(a) Random blood glucose levels of Tnfaip3^+/+, Tnfaip3^I325N/+ or Tnfaip3^I325N/I325N female (♀) or male (♂) mice at 8 or 12 weeks of age. (b, c) Blood glucose levels (mM) were monitored following an intraperitoneal injection of glucose (2 g/kg) in 12 week-old mice. (d, e) Pancreatic islets were isolated from individual mice of the indicated A20 genotypes, incubated overnight, and treated with 200 U/ml TNFα for the indicated times. (d) Representative immunoblot for phosphorylated JNK (pJNK) and total JNK (TJNK, loading control). Cumulative densitometry from 4 independent experiments is shown below. Columns represent mean ± s.e.m. Two-tailed Student t-test used for significance analysis, *P < 0.05. (e) Immunoblot for non-canonical NF-κB components NIK, p100/p52 and RelB; representative of 2 independent experiments. Tnfaip3^I325N/I325N islets exhibited increased activation of the non-canonical NF-κB pathway that can alter beta cell transcriptional programs to favor reduced insulin output³⁸.