Figure 5.

Tpl2 inhibition protects mouse islets from cytokine-induced death and alteration of glucose-induced insulin secretion. (a) Measurement of caspase-3/7 activity in mouse islets pretreated for 2 h without or with Tpl2-I (3 μM), and then incubated for 24 h without (Control, Ctrl) or with a cytokine mix (CK). (b) Measurement of DNA fragmentation in mouse islets treated as in (a). (c) Glucose-stimulated insulin secretion in mouse islets treated as in (a and b) (inclined and horizontal hatched boxes: glucose 3 mM (G3), white and black solid boxes: glucose 15 mM (G15)). Each column represents mean±S.E.M. of 6 to 8 mice analyzed. *P<0.05, and **P <0.01 versus relative indicated controls by one-way ANOVA. (d and e) Intracellular calcium concentration ([Ca²⁺]_c) changes monitored in perfused control islets incubated without or with 3 μM of Tpl2-I (d) or in perfused islets treated for 24 h with the cytokine mix, and incubated without or with Tpl2-I (3 μM) during 2 h before and during the CK treatment (e). Data are mean±S.E.M. of three experiments with three mice per group. (f) Correlation between insulin secretion and [Ca²⁺]_c