DEVELOPMENT OF THE INSULIN-SECRETION MECHANISM IN FETAL AND NEONATAL RAT PANCREATIC B-CELLS - RESPONSE TO GLUCOSE, K+, THEOPHYLLINE, AND CARBAMYLCHOLINE

We studied the development of the insulin secretion mechanism in the p ancreas of fetal ( 19- and 21-day-old), neonatal (3-day-old), and adul t (90-day-old) rats in response to stimulation with 8.3 or 16.7 mM glu cose, 30 mM K+, 5 mM theophylline (Theo) and 200 mu M carbamylcholine (Cch). No effect of glucose or high K+ was observed on the pancreas fr om 19-day-old fetuses, whereas Thee and Cch significantly increased in sulin secretion at this age (82 and 127% above basal levels, respectiv ely). High K+ also failed to alter the insulin secretion in the pancre as from 21-day-old fetuses, whereas 8.3 mM and 16.7 mM glucose signifi cantly stimulated insulin release by 41 and 54% above basal levels, re spectively. Similar results were obtained with Thee and Cch. A more ma rked effect of glucose on insulin secretion was observed in the pancre as of 3-day-old rats, reaching 84 and 179% above basal levels with 8.3 mM and 16.7 mM glucose, respectively. At this age, both Thee and Cch increased insulin secretion to close to two-times basal levels. In isl ets from adult rats, 8.3 mM and 16.7 mM glucose, Thee, and Cch increas ed the insulin release by 104, 193, 318 and 396% above basal levels, r espectively. These data indicate that pancreatic B-cells from 19-day-o ld fetuses were already sensitive to stimuli that use either cAMP or I F; and DAG as second messengers, but insensitive to stimuli such as gl ucose and high K+ that induce membrane depolarization. The greater eff ect of glucose on insulin secretion during the neonatal period indicat es that this period is crucial for the maturation of the glucose-sensi ng mechanism in B-cells.