Fetal and neonatal exposure to nicotine in Wistar rats results in increased beta cell apoptosis at birth and postnatal endocrine and metabolic changes associated with type 2 diabetes.
OBJECTIVE
Epidemiological studies report an increased risk of obesity and type 2 diabetes in children born to women who smoked during pregnancy. This study examines the effect of fetal and neonatal exposure to nicotine, the major addictive component of cigarettes, on postnatal growth, adiposity and glucose homeostasis.


METHODS
Female Wistar rats were given either saline (vehicle) or nicotine (1 mg kg(-1) day(-1)) during pregnancy and lactation. Serum and pancreas tissue were collected from the infant rats at birth. Postnatal growth was assessed weekly until the rats reached 26 weeks of age and glucose homeostasis was examined by OGTTs performed at 7 and 26 weeks of age.


RESULTS
Exposure to nicotine resulted in increased postnatal growth and adiposity. Nicotine exposure also resulted in dysglycaemia at 7 and 26 weeks of age. Serum insulin concentrations were decreased in the pups exposed to nicotine at birth. This was associated with increased beta cell apoptosis (pups of saline-treated mothers 8.8+/-1.21% apoptotic beta cells; pups of nicotine-treated mothers 27.8+/-3.1% apoptotic beta cells).


CONCLUSIONS
Fetal and neonatal exposure to nicotine results in metabolic changes in the offspring that are consistent with obesity and type 2 diabetes. We propose that these metabolic changes may be a consequence of the initial insult to the beta cell during fetal life and that this animal model has many characteristics of diabetes in humans.
Holloway
A C
AC
Department of Obstetrics and Gynecology, McMaster University, Rm 3N52 HSC 1200 Main Street W., Hamilton, ON, Canada, L8N 3Z5. hollow@mcmaster.ca
Lim
G E
GE
Petrik
J J
JJ
Foster
W G
WG
Morrison
K M
KM
Gerstein
H C
HC
D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006487:Hemostasis; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009538:Nicotine / Q000494:pharmacology*; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D009538:Nicotine; D005947:Glucose