Glucose Production and Glucose Disposal Integrated by an Intrinsic Inverse Coupling in Vivo: hypothesis of inter-organ reflex on glucose regulation

Glucose production (GP) and glucose disposal (Rd) are two decisive and fundamental parameters in glucose turnover and in glucose homeostasis regulation. In conventional theory, GP and Rd were responsive to regulatory factors respectively and independently of each other. Even though GP and Rd responded in reverse to insulin, GP for suppression and Rd for elevation, these inverse alterations used to be attributed to insulin multiple functions both on hepatic GP, directly or indirectly, and on whole-body glucose Rd. However, in the present study, we found GP and Rd were inversely coupled intrinsically no matter which side was the target of insulin by comparison of Rd and GP data pairs between peripheral vein insulin infusion protocol and portal vein insulin infusion protocol in rats. Furthermore, neither circulating NEFA nor HFD induced resistance broke the GP-Rd inverse coupling, but both of them reduced the responses of both GP and Rd to insulin. In conclusion, we provide the evidence that GP and Rd are two coupled parameters in vivo and they alter in reverse simultaneously, the mechanism under which needs further investigation but we tend to believe an inter-organ neural reflex was involved.