Hepatic Overexpression Of JAZF1Protects From Insulin Resistance And Gluconeogenesis In Db/db Mice

Objective To explore the effects of hepatic overexpression ofjuxtaposed with another zinc finger gene1(JAZF1) gene on glucose andlipids metabolism and gluconeogenesis in leptin receptor defection db/dbmice and its mechanism.Methods8-week-old db/db mice were randomly divided intodb/db-NS(n=6), db/db-vector(n=6), db/db-JAZF1(n=6). Age-matchedwild-type C57BL/6J mice were used as lean controls. Db/db mice wererespectively injected with saline, pIRES2-EGFP and recombinant plasmidpIRES2-EGFP-JAZF1via tail vein. Blood glucose level, body weight andfood intake were measured. The level of plasma and liver biochemicalparameters were analysed. The protein lever of insulin signaling,phosphoenolpyruvate carboxykinase and glucose-6-phosphatase in liverwere detected.Results The level of blood glucose and insulin were much higher indb/db diabetes mice (P<0.01), but JAZF1protein expression wasdown-regulated compared with age-matched lean control mice (P<0.01).After JAZF1gene overexpression, the level of blood glucose, insulin andcholesterol in plasma and liver in db/db-JAZF1group were significantlylower than those in db/db-NS and db/db-vector group (P<0.05). Increased hepatic JAZF1expression improves insulin sensitivity in vivo (P<0.05).The protein level of phosphoenolpyruvate carboxykinase andglucose-6-phosphatase in db/db-JAZF1group were decreased comparedwith those in db/db-NS and db/db-vector groups (P<0.05).Conclusion Hepatic overexpression of JAZF1improves thedisordered glucose and lipid metabolism in db/db diabetes mice, which isrelated with improved insulin signaling and decreased insulin resistanceand gluconeogenesis.