Portal glucose infusion in the mouse induces hypoglycemia - Evidence that the hepatoportal glucose sensor stimulates glucose utilization

To analyze the role of the murine hepatoportal glucose sensor in the contro l of whole-body glucose metabolism, we infused glucose at a rate correspond ing to the endogenous glucose production rate through the portal vein of co nscious mice (Po-mice) that were fasted for 6 h. Mice infused with glucose at the same rate through the femoral vein (Fe-mice) and mice infused with a saline solution (Sal-mice) were used as controls. In Po-mice, hypoglycemia progressively developed until glucose levels dropped to a nadir of 2.3 +/- 0.1 mmol/l, whereas in Fe-mice, glycemia rapidly and transiently developed , and glucose levels increased to 7.7 +/- 0.6 mmol/l before progressively r eturning to fasting glycemic levels. Plasma insulin levels were similar in both Po- and Fe-mice during and at the end of the infusion periods (21.2 +/ - 2.2 vs. 25.7 +/- 0.9 mu U/ml, respectively, at 180 min of infusion). The whole-body glucose turnover rate was significantly higher in Po-mice than i n Fe-mice (45.9 +/- 3.8 vs. 37.7 +/- 2.0 mg kg(-1) min(-1), respectively) a nd in Sal-mice (24.4 +/- 1.8 mg kg(-1) min(-1)). Somatostatin co-infusion w ith glucose in Po-mice prevented hypoglycemia without modifying the plasma insulin profile. Finally, tissue glucose clearance, which was determined af ter injecting C-14-2-deoxyglucose, increased to a higher level in Po-mice v ersus Fe-mice in the heart, brown adipose tissue, and the soleus muscle. Ou r data show that stimulation of the hepatoportal glucose sensor induced hyp oglycemia and increased glucose utilization by a combination of insulin-dep endent and insulin-independent or -sensitizing mechanisms. Furthermore, act ivation of the glucose sensor and/or transmission of its signal to target t issues can be blocked by somatostatin.