Evaluation of the pancreatic B-cell function in the rat after prenatal exposure to streptozotocin or N-nitrosomethylurea.
Female rats were treated with calibrated doses of N-nitrosomethylurea (NMU) or streptozotocin (STZ) at the end of their pregnancy (20.5 day post coïtum) and the pancreatic B-cell function in their progeny was studied. We also investigated whether or not these nitrosamines were able to directly damage fetal B-cell function using isolated fetal islets maintained in vitro. STZ (1 mM) was found to be cytotoxic toward B-cell function in fetal islets maintained in vitro: inhibitory effect on both glucose-stimulated insulin biosynthesis and release were observed. NMU (1 mM) exhibited a similar though less toxic effect. So the question was raised as to whether any toxicity against the B cells in the fetus can develop upon exposure of the pregnant mother to these nitrosamines. STZ administration (35 mg/Kg) to pregnant mothers exerted clear-cut effects on the endocrine pancreas of their offspring: their pancreatic insulin stores were decreased by 35% when measured 1 day after birth. This alteration was maintained: in 2 month-old offspring a mild hyperglycemia (9.9 +/- 0.3 vs 8.5 +/- 0.2 mM in control rats, p less than 0.01), a decrease of the pancreatic insulin stores (by 45%) and an impaired insulin secretion in response to glucose and arginine was observed. These defects were only detectable in the male progeny. NMU administration (30 or 50 mg/Kg) to pregnant mothers did not produce in the offspring any significant alteration of their pancreatic insulin stores and plasma glucose levels, what the ages considered (1 day or 2 months).(ABSTRACT TRUNCATED AT 250 WORDS)
Serradas
P
P
Laboratoire de Physiologie du Développement UA CNRS n0 307, Université Paris.
Giroix
M H
MH
Portha
B
B
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008770:Methylnitrosourea / Q000494:pharmacology*; D010477:Perfusion; D010649:Phenylalanine / Q000378:metabolism; D011384:Proinsulin / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology*
D007328:Insulin; D010649:Phenylalanine; D013311:Streptozocin; D008770:Methylnitrosourea; D011384:Proinsulin