The Effect Of Central Vaspin On Glucose Metabolism In Diet-induced Insulin Resistance Rats

Objective To investigate the acute effect of central vaspin on hepaticglucose homeostasis and insulin sensitivity in diet-induced insulinresistance ratsMethods Male Sprague-Dawley(SD) rats were randomly divided into10groups. The groups were as follows:1) NCD-V3-ACF (NCA group;n=10);2) NCD-V3-vaspin (NCV group; n=10);3) HFD-V3-ACF (HFAgroup; n=10);4) HFD-V3-vaspin(HFV group; n=10);5) HFD-V3-vaspin+HV(n=5);6) HFD-V3-ACF+HV(n=5);7) HFD-V3-vaspin+sham(n=5);8)HFD-V3-ACF+sham(n=5). All rats were fed either a normal-chow-diet(NCD) or a high-fat-diet (HFD)for10weeks. All groups of rats werestereotaxically implanted with indwelling catheters into the third cerebralventricle (ICV). Furthermore, a separate cohort of rats were subjected tohepatic branch vagotomy (HVG) or to sham operation (SHAM). Glucosekinetics were evaluated by hyperinsulinemic-euglycemic clamp techniquewith [3-3H]glucose and [U-14C]-lactate as the tracer in conscious rats.Results Compared to NCD-fed groups, body weight，FIns, FFA, TG,TC, LDL-C levels were significantly increased in HFD-fed groups(P<0.01).During the clamp steady-state, glucose infusion rate（GIR）and glucosedisposal rate（GRd）in HFV group was significantly increased compared to HFA group； hepatic glucose production （HGP）， G6Pase Flux，gluconeogenesis was significantly decreased compared to HFA group；whilethe glucose cycling and glycogenolysis was not changed between HFV andHFA groups. Surprisingly, all above indexs reflected the glucose kineticshad no significant difference between NCA and NCV groups. In the fourgroups of rats undergo hepatic branch vagotomy (HVG) or sham operation(SHAM), GIR and GRd was significantly increased inHFD-V3-Vaspin+sham group compared with the other three groups, HGPwas significantly decreased compared with the other three groups.Conclusion The glucose kinetics and insulin sensitivity can beimproved by acute administration of vaspin into the V3in HFD-fed rats.Selective hepatic branch vagotomy (HVAG) blocked the ability of centralvaspin to reduce hepatic glucose production in HFD-fed rats. Therefore, wecan reasonably conclude that vaspin triggers a brain-liver circuit via thehepatic branch of the vagus nerve to inhibit glucose production andimprove insulin resistance.