Effect of superfused insulin on cerebral cortical glucose utilization in awake goats

The effect on cortical cerebral glucose utilization (CMRglu) of intracerebral insulin administration in awake goats was studied. The insulin was superfused in a mock cerebrospinal fluid (CSF) employing chronically implanted cranial windows. Two windows were implanted bilaterally: one window over an equivalent portion of each parietal cortex. With one window used to deliver insulin/CSF and the other used to simultaneously deliver CSF alone (control), changes in CMRglu were assessed using a modification of a sequential 2-[3H]- then 2[14C]deoxy-D-glucose (2DG) technique originally described by Altenau and Agranoff. Initial experiments employing 125I-insulin demonstrated that the superfusion procedure increased insulin levels only in the outer 1 mm of cortical tissue exposed to insulin containing perfusate. Additional preliminary evaluations, using conditions known to alter CMRglu, generally established that present methods were adequate to induce and detect CMRglu changes. However, it was also shown experimentally and using a mathematical model that 2-[3H]DG test/control tissue ratios could be influenced by subsequent changes in CMRglu and the dephosphorylation rate. Thus 3H ratios could not be used to establish preexperimental test/control CMRglu relationships as the originally devised model assumed but could be employed to indicate changes in dephosphorylation. The mathematical model allowed for improved estimates of CMRglu changes from 2[14C]DG/2-[3H]DG test over control tissue ratios. Even with these corrections, insulin was estimated to cause no more than an 8-15% increase in cortical CMRglu. A very limited role for insulin, at least in cerebral cortical metabolic regulation, is thus indicated