Insulin secretion by fetal human pancreas in organ culture.

Whole fetal human pancreases of 12-22 weeks gestation, showed histological growth and differentiation in vitro over 3 weeks. At glucose concentrations of 1-4 g/l, there was no difference in insulin secretion into culture medium over 1 h. There was no stimulation of insulin release by D-glyceraldehyde, thus defective glucose-stimulated insulin release was probably not due to impairment of an early step in glycolysis. In the presence of 0.5 mmol/l dibutyryl cyclic AMP, insulin secretion was enhanced (0.188±0.030 versus 0.100±0.012 mU·mg tissue·h, p<0.001) independently of glucose concentrations. It thus appears that impairment of glucose-stimulated insulin release was unlikely to be due to insufficient intracellular cyclic AMP. Insulin release increased in response to tolbutamide and theophylline. Insulin secretion was stimulated in the presence of a fivefold increase in amino acid concentration (0.118±0.018 versus 0.031±0.008 mU·mg tissue ·h, p<0.001). There was a fourfold increase in basal insulin secretion from islets previously grown in high concentration of amino acids compared with standard culture medium, (0.284±0.052 versus 0.067±0.011 mU·mg tissue·h, p<0.001), emphasizing the important role of amino acids as substrates for B cell metabolism and development. [ABSTRACT FROM AUTHOR]