The Effects Of Central Over-Expression JAZF1 On Glucose Metabolism In Diet-Induced Insulin Resistance Rats And Potential Mechanisms

Objective To investigate the effects of central Ad-JAZF1 injection on hepatic glucose homeostasis and insulin sensitivity in diet-induced insulin resistance rats and the mechanisms of neural pathways.Method Male Sprague-Dawley(SD) rats were randomly divided into these groups, just as follows:1) NCD+aCSF (NCD-aCSF group; n=22); 2) NCD+Ad-GFP (NCD-Ad-GFP group; n=28); 3) NCD+Ad-JAZF1 (NCD-Ad-JAZF1 group; n=28); 4) HFD+aCSF (HFD-aCSF group; n=22); 5) HFD+Ad-GFP (HFD-Ad-GFP group; n=28); 6)HFD +Ad-JAZF1 (HFD-Ad-JAZF1 group, n=28); 7) HFD+Ad-GFP+SHAM (HFD-Ad-GFP-SHAM group, n=6); 8) HFD+Ad-JAZF1+SHAM(HFD-Ad-JAZF1-SHAM group, n=6); 9) HFD+Ad-GFP+HVG(HFD-Ad-GFP-HVG group, n=6); 10) HFD+Ad-JAZF1+HVG (HFD-Ad-JAZF1-HVG group, n=6); 11) HFD+Ad-JAZF1+GLI (HFD-Ad-JAZF1-GLI group, n=6); 12) HFD+Ad-GFP+GLI (HFD-Ad-GFP-GLI group, n=6); 13) HFD+Ad-JAZF1+AICAR (HFD-Ad-JAZF1-AICAR group, n=6); 14) HFD+Ad-GFP+AICAR(HFD-Ad-GFP-AICAR group, n=6). The insulin resistance induced by high fat diet. All rats were stereotaxically impl-anted with indwelling catheters into the medial hypothalamus base. Furthermore, some rats were subjected to hepatic branch vagotomy or sham operation. Glucose and lipid metabolism, insulin sensitivity wer-e estimated by using intraperitoneal glucose tolerance test and hyperi-nsulinemic-euglycemic clamp studies in conscious rats.Results Compared to NCD-fed groups, body weight, FBG, Ins, TC, TG, FFA levels were significantly increased in HFD-fed groups; VO2, VCO2 and RER were significantly decreased in HFD-fed rats groups (all P<0.01). Compared to HFD-Ad-GFP group, body weight, food intake, Ins, RER was significantly decreased in HFD-Ad-JAZF1 group (P<0.05 or P <0.01). VO2 and VCO2 of HFD-Ad-JAZF1 group were significantly higher than those of HFD-Ad-GFP group (P< 0.01). During the intraperitoneal glucose tolerance (IPGTT), the area under the curve (AUC) of glucose or inslin in HFD-Ad-JAZF1 group were lower than HFD-Ad-GFP group’s (P<0.01). During the clamp steady state, glucose infusion rate (GIR), glucose disposal rate (GRd) and the percentage suppression of hepatic glucose production in HFD-Ad-JAZF1 group was significantly increased compared to HFD-aCSF or HFD-Ad-GFP group. And the hepatic glucose production (HGP) was significantly decreased compared to HFD-aCSF or HFD-Ad-GFP group (P<0.01). But there was no significant differences in NCD-fed rats. During the Ad-JAZF1 treated rats, the sham group had an increasing GIR, GRd and an inhibition in the rate of glucose production(P<0.01). Then MBH infusion of glibenclamide significantly reversed the effect of central JAZF1 on hepatic glucose production(P<0.01). When the AMPK activator AICAR was lactated into the MBH, GIR, GRd and the percentage suppression of HGP in HFD-Ad-JAZF1-AICAR group were significantly decreased compared with HFD-Ad-JAZF1 group (P< 0.01). And HGP of HFD-Ad-JAZF1-AICAR group was increased compared with HFD-Ad-JAZF1 group(P<0.05).Conclusion Central over-expression of JAZF1 improve insulin resistance and hepatic glucose metabolism disorder by brain-liver axle.