Chronic Hyperglycemia and the Human Fetal β Cell

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Abstract

Summary

It is well known that the ability of the immature rodent fetal p cell to release insulin in response to a glucose challenge can be enhanced by chronic exposure to a high concentration of glucose in vitro. It might be thought that the human fetal p cell would mature similarly 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 pancreatic explants to as high a concentration of glucose as 30 mM did not cause significant enhancement of the insulinogenic response to an acute challenge with 20 mM glucose. In contrast, chronic insulin release was enhanced, although culture medium containing 2.8 mM glucose was equally as efficacious as that with 30 mM glucose. Just as with insulin, proinsulin levels in the culture media containing no glucose also were suppressed. Degranulation of the p cell exposed to high concentrations 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 but not 2.8 mM glucose. Desensitization to the acute stimulatory effect of 10 mM theophylline did not eventuate, even in explants exposed to 30 mM glucose. In contrast to the human explants, rat fetal pancreatic explants did mature when exposed to 1 1.2 mM glucose for 1 week. In summary, our studies on the human fetal β cell show that (a) 6 weeks of exposure to high glucose levels is insufficient to mature it; (b) some 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 β cell. Thus, it would seem that there is no practical advantage to exposing human fetal pancreatic explants to high levels of glucose before grafting them.

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