Figure 4.

DDR through ATM induces proinflammatory cytokine expression in islets. A: Heat map presentation of qPCR of T1D-associated cytokines. Cultured mouse islets were treated with 5 mmol/L STZ or TNF-α for 1 h (pools of three different mice each). The t test P values are listed for each gene. B: Heat map presentation of qPCR of T1D-associated cytokines. Islets were harvested and analyzed after five daily STZ injections (20 mg/kg). The t test P values are listed for each gene. C: qPCR analysis of Cxcl10 performed on isolated wild-type mouse islets treated with 5 mmol/L STZ and 10 μmol/L KU55933 (ATMi) for 48 h. Error bars represent 1 SEM. Only statistically significant relations are connected. Also shown is an ELISA analysis of IP-10 performed on medium supernatants from the same experiment. Error bars represent 1 SEM. Only statistically significant relations are connected. D: qPCR analyses of IL-1β and Cxcl10 performed on islets from wild-type mice, untreated (NT) (saline injections) mice, and mice injected with caffeine (50 mg/kg), injected with STZ (20 mg/kg), and coinjected with STZ and caffeine (STZ-caffeine). All treatments were given for 5 consecutive days. Mice were sacrificed after the last injection. Error bars represent 1 SEM. Only statistically significant relations are connected. E: qPCR analyses of IL-1β and Cxcl10 performed on islets from NT wild-type mice (saline injections), wild-type mice injected with STZ (STZ-WT), and ATM^ΔBC mice injected with STZ (STZ-ATM^ΔBC). STZ (20 mg/kg) was injected for 5 consecutive days. Mice were sacrificed after the last injection. Error bars represent 1 SEM. Only statistically significant relations are connected.