Concordant induction of rapid in vivo pulsatile insulin secretion by recurrent punctuated glucose infusions

Insulin is largely secreted as serial secretory bursts superimposed on basa l release, insulin secretion is regulated through changes of pulse mass and frequency, and the insulin release pattern affects insulin action. Coordin ate insulin release is preserved in the isolated perfused pancreas, suggest ing intrapancreatic coordination. However, occurrence of glucose concentrat ion oscillations may influence the process in vivo, as it does for ultradia n oscillations. To determine if rapid pulsatile insulin release may be indu ced by minimal glucose infusions and to define the necessary glucose quanti ty, we studied six healthy individuals during brief repetitive glucose infu sions of 6 and 2 mg.kg(-1).min(-1) for 1 min every 10 min. The higher dose completely synchronized pulsatile insulin release at modest plasma glucose changes (similar to 0.3 mM = similar to 5%), with large (similar to 100%) a mplitude insulin pulses at every single glucose induction (n = 54) at a lag time of 2 min (P < 0.05), compared with small (10%) and rare (n = 3) unind uced insulin excursions. The smaller glucose dose induced insulin pulses at lower significance levels and with considerable breakthrough insulin relea se. Periodicity shift, from either 7- to 12-min or from 12- to 7-min interv als between consecutive glucose (6 mg.kg(-1).min(-1)) infusions in six volu nteers revealed rapid frequency changes. The orderliness of insulin release as estimated by approximate entropy (1.459 +/- 0.009 vs. 1.549 +/- 0.027, P = 0.016) was significantly improved by glucose pulse induction (n = 6; 6 mg.kg(-1).min(-1)) compared with unstimulated insulin profiles (n = 7). We conclude that rapid in vivo oscillations in glucose may be an important reg ulator of pulsatile insulin secretion in humans and that the use of an inte rmittent pulsed glucose induction to evoke defined and recurrent insulin se cretory signals may be a useful tool to unveil more subtle defects in beta- cell glucose sensitivity.