Effect of normoglycemia on the functional maturation of the human fetal beta cell

Previous studies from this laboratory have shown that human fetal pancreas of gestational age 14-20 weeks was capable not only of growing but also of maturing in its insulinogenic response to an acute static challenge with glucose, once it was removed from its usual physiological environment and passaged for up to 37 weeks in the diabetic nude mouse (absolute age of 58 weeks, where absolute age = gestational age + duration of passage in the mouse). In order to analyze the dynamics of insulin secretion during this process of maturation, these experiments were repeated, the tissue being perifused after removal from the mouse. Normoglycemic nude mice rather than diabetic ones were used because of their hardier nature. Human fetal pancreata of gestational age 14-20 weeks were passaged in these normoglycemic animals, either subcutaneously or beneath the renal capsule, for 11 to 70 weeks (absolute age up to 86 weeks). The tissue was removed and, after a mean of 1 day in organ culture, perifused for 50 min with 20 mmol/L of glucose. While overall there was a slight but significant increase in insulin secretion over basal levels, there was no time-dependent maturation of the response to glucose, and no adult-type response at any stage, as occurs both physiologically and in tissue passaged in the diabetic nude mouse by this period.(ABSTRACT TRUNCATED AT 250 WORDS)