Biphasic insulin release from perifused cultured fetal rat pancreas. Effects of glucose, pyruvate, and theophylline.

Abstract

Recent interest in the dynamics of insulin release in the adult has prompted the investigation of immunoreactive insulin (IRI) release profiles during perifusion of cultured fetal rat pancreas, a preparation previously studied extensively in a static incubation system. Glucose alone (16.4 mM) induced an early (primary) IRI release response and a minimal later (secondary) response. Pyruvate alone (16.4 mM) evoked no response above baseline. Addition of 2.5 mM theophylline to either of these substrates resulted in enhanced and biphasic IRI release, the theophylline effect occurring predominantly in the second phase. With glucose as substrate, increasing the theophylline concentration to 10 mM caused similar enhancement of the primary response, but less enhancement of the secondary response, by comparison with 2.5 mM theophylline. By contrast, 10 mM theophylline further enhanced the secondary response to pyruvate. Hence, this preparation of cultured fetal rat pancreas resembled adult rat pancreas with respect to the first phase of IRI release in response to glucose. However, the much smaller secondary response to glucose alone contrasted markedly with that of the adult, and appears to explain the relatively poor responsiveness to glucose of fetal and newborn rat pancreas during incubation.