Beta-cell growth in adolescent and adult rats treated with streptozotocin during the neonatal period.
Regeneration of neonatal beta cells after subtotal streptozotocin (STZ)-induced destruction is incomplete but nevertheless leads to rapid remission of hyperglycaemia. To study the proliferative and functional capacity of regenerated beta cells in adolescent and adult rats after early beta-cell damage and to determine the time point after birth which is decisive for regeneration, beta-cell growth and metabolic capacity were analysed in rats treated during the neonatal period with STZ (100 micrograms/g body weight) and studied over 3 to 20 weeks. Using immunocytochemistry combined with morphometry we found that the regenerated beta cells continue to increase in number till week 6 of life, when they reached values of more than 50% of those of controls. After week 6, the regenerated beta cells had enlarged in size but failed to further increase their number, although their proliferative activity, determined by bromodeoxyuridine (BrdU) pulse labelling, was still higher at 6 and 10 weeks than that of normal rats. The inability of regenerated beta cells to further increase their number coincided with a deterioration of their function (week 10, male rats; week 20, female rats). When beta cells were destroyed on day 2 or 5 instead of the day of birth, regeneration of beta cells markedly decreased and the rats were already on the threshold of development of glucose intolerance at 3 weeks of age. We concluded that the partially regenerated beta-cell population in rats treated with STZ on the day of birth ceases to grow 10 to 20 weeks later. This growth arrest may be due to the sustained functional demand to which these beta cells are exposed in order to compensate for their reduced number. Beta-cell capacity for regeneration declines rapidly during the first days of life.
Wang
R N
RN
Department of Experimental Pathology, Free University of Brussels, Belgium.
Bouwens
L
L
Klöppel
G
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012727:Sex Characteristics; D013311:Streptozocin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin