Effect of glucose-dependent insulinotropic polypeptide on whole-body glucose utilization in sheep

Four adult Corriedale sheep were used in an experiment divided into three p arts. In part 1 a primed continuous infusion of [6,6-H-2(2)]glucose was inf used for 7 h. The first 3 h was the control period, from 3 to 7 h glucose-d ependent insulinotropic polypeptide (GIP) was infused, and from 5 to 7 h so matostatin was infused. Part 2 of the experiment was the same as for part 1 except that insulin was infused between 3 h and 7 h and GIP was infused be tween 5 and 7 h. Coincident with the insulin infusion, normal glucose was a lso infused at a variable rate in order to keep the plasma glucose at basal levels. In part 3 of the experiment [6,6-H-2(2)]glucose was infused for 5 h and somatostatin was infused between 3 and 5 h. Measurements of glucose t urnover were made in the last 40 min of the control, GIP only, insulin only , somatostatin only, GIP plus somatostatin and GIP plus insulin infusion pe riods. Plasma insulin levels were reduced to the limit of detection by the somatostatin infusion; under such conditions whole-body glucose uptake shou ld be entirely non-insulin-mediated (NIMGU). Expressing glucose disposal as glucose metabolic clearance rate demonstrated that elevated, but still phy siological GIP levels had no effect on NIMGU but significantly increased in sulin-mediated glucose uptake when plasma insulin levels were similar to le vels typically observed after a meal. These results indicate that in sheep, GIP may enhance insulin action with respect to glucose disposal following a meal, but has no effect on glucose disposal pathways not responsive to in sulin.