Importance of preabsorptive insulin release on oral glucose tolerance: studies in pancreatic islet transplanted rats

Abstract

The role of preabsorptive (cephalic phase) insulin release in oral glucose tolerance was investigated using diabetic rats treated by intraportal transplantation of isogenic islets. This early neurally mediated phase of insulin release has been shown to be absent in such rats. When the body weight of transplanted rats was normalised, glucose tolerance tests (GTTs) were performed in the unstressed state using permanent cardiac catheters. Transplanted rats had a normalised intravenous GTT, whereas, as we have shown previously, their oral GTT remained clearly pathological. During both tests peripheral insulin levels were decreased compared with controls. While during intravenous GTT the onset of insulin release occurred as early in transplanted rats as in controls, during oral GTT there was a clear delay, probably because of the absence of the cephalic phase. Re-establishment of normal preabsorptive insulin levels was attempted by a small intravenous insulin injection during this period. This resulted in a transient increase in peripheral insulin levels, which, at two minutes after glucose ingestion, gave values similar to those found in controls at that time. This small insulin injection caused a marked improvement of the oral GTT which was most evident after exogenous insulin had disappeared from the blood. While the injection did not affect the 60 minute incremental insulin area, the glucose area was decreased by 50%, to a value not significantly different from that of control rats. The cephalic phase of insulin release appears, therefore, to be one important factor in the control of glycaemia during food intake. Its absence plays a major role in the pathological oral glucose tolerance of diabetic rats treated by intraportal islet transplantation.