BIPHASIC INSULIN-SECRETION DURING INTRAVENOUS GLUCOSE-TOLERANCE TEST PROMOTES OPTIMAL INTERSTITIAL INSULIN PROFILE

We examined the hindlimb lymph insulin profile during simulated intrav enous glucose tolerance tests (IVGTTs) in anesthetized dogs to test th e following hypotheses: 1) the biphasic insulin response to intravenou s glucose can be seen as a priming bolus and a secondary infusion that effect a rapid stepwise increase in the interstitial insulin concentr ation and 2) the activation of glucose utilization (rate of glucose up take [R-d]) during an IVGTT is more similar to the dynamics of the int erstitial insulin profile than that of the arterial plasma. Three insu lin profiles mere infused: a normal biphasic pattern, a second phase i nfusion only, and a biphasic pattern with a fourfold greater first pha se and a normal second phase. During the normal biphasic infusion, lym ph insulin quickly reached and maintained a steady-state concentration (10 min, 26.42 +/- 0.86 mu U/ml). With second phase only, it took lym ph insulin 35 min to reach a steady state of lower con centration (13. 13 +/- 0.46 mu U/ml) than the normal. And with a fourfold greater firs t phase, lymph insulin plateaued quickly (16 min, 140.87 +/- 1.68 mu U /ml), but for a shorter duration than the normal. For each profile, th e time course of activation of R-d did not follow the time course of i nsulin in the plasma, but nas more similar to that of insulin in the i nterstitial fluid. These results show that the biphasic response allow s interstitial insulin to rapidly reach and maintain a steady state be neficial to activation and maintenance of glucose utilization.