Sensitized effect of prestimulation on insulin release from the perifused rat islets with a slow-rise glucose...

The sensitized effect of prestimulation with 16.7 mM glucose on insulin release with a slow-rise glucose stimulation from the perifused rat islets of Langerhans was studied, together with the kinetic analysis of insulin release, and the interrelationship between the prestimulation time and the maximal rate of insulin release. All dose-response relationships which were derived from the dynamics of insulin release from islets prestimulated over various time periods within 60 min, showed sigmoidal profiles. Kinetic analyses were performed with Lineweaver-Burk's and Hill's equations. The 30-min prestimulation significantly reduced Hill's constant (n) from 6.2 +/- 0.7 of the control to 3.7 +/- 0.6 (p less than 0.05) and also enhanced the logarithmic equilibrium constant (log K) from -5.4 +/- 0.6 mM-n to -3.7 +/- 0.6 mM-n (p less than 0.05). However, the Km value was almost the same as that of the control (7.3 +/- 0.5 mM). On the other hand, the 60-min prestimulation remarkably diminished the Km value and the maximal rate of insulin release to 5.3 +/- 0.4 mM (p less than 0.05) and 0.6 +/- 0.08 muU/ml/islet/min (p less than 0.005), respectively. The maximal rate of insulin release linearly increased in proportion to the prestimulation time within 30 min. In conclusion, these results suggested that there would be some regularity depending on the prestimulation time in the process of transmission of the insulin-releasing signal in the pancreatic B cell and the accumulation of insulin into the provisional pool such as the labile insulin.