Effects of human placental lactogen and growth hormone on the production of insulin and somatomedin C/insulin-like growth factor I by human fetal pancreas in tissue culture

Abstract

ABSTRACT We have investigated the ability of glucose, human GH and human placental lactogen (hPL) to alter the content and release of somatomedin C/insulin-like growth factor I (SM-C/IGF-I), and the biosynthesis, content and release of insulin from cultured human fetal pancreas. Fetal pancreatic explants obtained from glands following prostaglandin-induced abortion between 12 and 21 weeks of gestation were maintained in free-floating culture for 3–5 days before the experiments. The explants were then cultured for 3 days in medium containing either 2·7 or 16·7 mmol glucose/l with or without GH (4·5 or 45·5 nmol/l) or hPL (4·6 or 46·5 nmol/l). Serum-free medium from the final 24 h of culture was collected and SM-C/IGF-I and insulin were measured radioimmunologically in both conditioned medium and tissue explants extracted with acid ethanol. Insulin biosynthesis, determined by immunoprecipitation of [3H]leucine incorporated into insulin, was not significantly altered by any experimental variable. Incubation in the presence of 16·7 mmol glucose/l caused an increase of insulin release from explants, but had no consistent action on insulin content, compared with medium containing 2·7 mmol glucose/l. The pancreatic content and release of SM-C/IGF-I were independent of these glucose concentrations. Neither GH nor hPL altered insulin or SM-C/IGF-I content or release in the presence of the lower glucose concentration. At the higher glucose concentration, 45·5 nmol GH/1 did not alter insulin release but caused a significant increase in SM-C/IGF-I content. When present with 16·7 mmol glucose/l hPL (46·5 nmol/l) promoted significant increases in both insulin content and release (59 and 47% respectively) and significantly increased pancreatic SM-C/IGF-I content and release (114and 117% respectively). The results suggest that, during tissue culture, glucose enhances the insulin output of human fetal pancreatic explants obtained in the second trimester. The ability of hPL to modulate B-cell function raises the possibility that this peptide may contribute to pancreatic development during fetal life and to total fetal body growth by increasing insulin production. J. Endocr. (1987) 113, 297–303