Fig. 5. ETV5 as a CRL4^COP1 regulated physiologic checkpoint for nutrient/glucose-induced insulin secretion.

a Refeeding induces CRL4B–COP1 complex formation in overnight-fasted mice. b Levels of ETV4 and ETV5 in the pancreas of mice fasted for the indicated period. c Levels of ETV5 in the pancreas of overnight-fasted mice, with/without refeeding. d Immunostaining of ETV5 in pancreatic tissues of fasted or fed mice (n = 5, ***p < 0.001, Student’s t test). Data are presented as mean ± SEM. e Effect of glucose (1.5 mg/kg) on ETV5 levels in pancreas. Scare bars, 0.2 μm. f Levels of ETV5 in isolated islets after exposure to different concentrations of glucose for 1 h. g Levels of ETV5 in the pancreas of starved/refed mice with/without MLN4924 pretreatment (15 mg/kg, 1 h). h Increasing glucose concentration in culture medium promotes Cul4 neddylation in islets.