Effects of caspase-1 inhibition on fasting glucose and insulin and glucose tolerance. LDLR−/−.Leiden mice were fed a high-fat diet for 21 weeks (HFD; n=15) or HFD+caspase-1 inhibitor Ac-YVAD-cmk (40 mg kg−1 daily) starting treatment after 9 weeks of HFD (HFD+YVAD; n=15). Low-fat diet (LFD)-fed mice (n=15) were included as a reference. (a) HFD-induced increases in fasted blood glucose relative to treatment start (t=9 weeks) were reduced in HFD+YVAD. (b) HFD-induced increases in fasted plasma insulin relative to treatment start (t=9 weeks) were reduced in HFD+YVAD. (c) The glucose response to an intraperitoneal glucose tolerance test (ipGTT; performed at t=20 weeks) was modified by caspase-1 inhibition. (d) HFD mice showed a clear insulin response during the ipGTT, whereas HFD+YVAD mice showed no response in plasma insulin. Data are mean±s.e.m. *P<0.05, **P<0.01, ***P<0.001 compared with HFD at the same time point.