CHRONIC HYPERGLYCEMIA AND THE HUMAN FETAL BETA-CELL

It is well known that the ability of the immature rodent fetal beta ce ll to release insulin in response to a glucose challenge can be enhanc ed by chronic exposure to a high concentration of glucose in vitro. It might be thought that the human fetal beta cell would mature similarl y in vitro, because neonates born of diabetic mothers release insulin in a more mature manner than normal infants. Using an organ culture of human fetal pancreatic explants, we have examined this possibility by exposing the tissue to 0-30 mM glucose. Six weeks of exposure of panc reatic explants to as high a concentration of glucose as 30 mM did not cause significant enhancement of the insulinogenic response to an acu te challenge with 20 mM glucose. In contrast, chronic insulin release was enhanced, although culture medium containing 2.8 mM glucose was eq ually as efficacious as that with 30 mM glucose. Just as with insulin, proinsulin levels in the culture media containing no glucose also wer e suppressed. Degranulation of the beta cell exposed to high concentra tions of glucose did not occur, the insulin content of the explants at the end of culture being enhanced in those maintained in 5.6-30 mM bu t not 2.8 mM glucose. Desensitization to the acute stimulatory effect of 10 mM theophylline did not eventuate, even in explants exposed to 3 0 mM glucose. In contrast to the human explants, rat fetal pancreatic explants did mature when exposed to 11.2 mM glucose for 1 week. In sum mary, our studies on the human fetal beta cell show that (a) 6 weeks o f exposure to high glucose levels is insufficient to mature it; (b) so me glucose recognition does occur concerning chronic insulin release; and (c) degranulation and desensitization do not result from exposure to high glucose levels, unlike what has been described for the adult b eta cell. Thus, it would seem that there is no practical advantage to exposing human fetal pancreatic explants to high levels of glucose bef ore grafting them.