Correlations between blood glucose levels and bromodeoxyuridine labelling indices of pancreatic islet cells following streptozotocin administration to pregnant Syrian golden hamsters.
Eighteen timed-pregnant Syrian golden hamsters were injected subcutaneously with streptozotocin (STZ, 60 mg/kg bw) early on gestational day 10. The response varied widely, and based on changes in blood glucose levels during gestational days 11 to 15, the hamsters were categorized into four groups: 1) no change; 2) mild diabetes (200-250 mg/dl), which reverted; 3) moderate diabetes (greater than 300 mg/dl), which reverted; and 4) moderate to severe diabetes (300-500 mg/dl), which was sustained. Two hours before sacrifice, a 25 mg tablet of bromodeoxyuridine (BrdU) was implanted subcutaneously into each experimental hamster and into 17 control pregnant hamsters that had not received STZ. BrdU-labelling was demonstrated immunochemically in the pancreatic islet cells. In control hamsters, the mean labelling index (LI) of the islet cells was 0.07% and did not exceed 0.2% in any hamster. Following injection of STZ, islet cell LI's remained low (0.13%) if the blood glucose levels were not altered by the diabetogenic drug. However, LI's were increased in islet cells of hamsters which showed a mild to moderate diabetes which rapidly reverted; the highest LI's (5% +/- 2.1) occurred in four hamsters that were killed 2 days after receiving STZ. The LI's were moderately increased (1.4% +/- 0.42) in two hamsters with moderate diabetes killed 2 days after STZ, but LI's were low (0.12% +/- 0.04) in six hamsters with moderate to severe diabetes killed 3, 4, and 5 days after STZ. Reversion of hyperglycemia to normoglycemia correlated closely with increased DNA synthesis in the islet cells of the pregnant hamsters. These observations strongly suggest that following mild cytotoxic injury induced by STZ, the B cells regenerated and insulin production was restored sufficiently to maintain normoglycemia.
McDowell
E M
EM
Department of Pathology, School of Medicine, University of Maryland, School of Medicine, Baltimore 21201.
DeSanti
A M
AM
Strum
J M
JM
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism / Q000473:pathology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005865:Gestational Age; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008647:Mesocricetus; D011247:Pregnancy; D013311:Streptozocin / Q000494:pharmacology*
D001786:Blood Glucose; D013311:Streptozocin; D001973:Bromodeoxyuridine