Rosiglitazone prevents diabetes by increasing beta-cell mass in an animal model of type 2 diabetes characterized by reduced beta-cell mass at birth.
OBJECTIVE
Interventions that preserve or increase beta-cell mass may also prevent type 2 diabetes. Rosiglitazone prevents diabetes in people with high glucose levels who have impaired glucose tolerance and/or impaired fasting glucose. The effect of this drug on both glucose levels and beta-cell mass was studied in a rat model of diabetes, characterized by reduced beta-cell mass at birth with normoglycaemia, and progression to dysglycaemia with age.


METHODS
Female Wistar rats were given either saline (vehicle) or nicotine during pregnancy and lactation. Offspring of saline-exposed dams were given vehicle and offspring of nicotine-exposed dams were randomized to receive either vehicle or rosiglitazone starting at weaning. Beta-cell mass, proliferation and apoptosis were determined at birth and at 4 and 26 weeks of age. Glucose homeostasis was examined following sequential oral glucose tolerance tests (OGTT).


RESULTS
Rosiglitazone treatment prevented the development of dysglycaemia in nicotine-exposed animals. The ability of rosiglitazone to preserve normoglycaemia appeared to be because of its ability to increase beta-cell mass through a combination of enhanced beta-cell proliferation and decreased beta-cell apoptosis.


CONCLUSIONS
These results suggest that if rosiglitazone administration is started prior to the onset of glucometabolic abnormalities, it prevents the onset of dysglycaemia by partially restoring beta-cell mass in animals with reduced beta-cell mass at birth.
Holloway
A C
AC
Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada. hollow@mcmaster.ca
Petrik
J J
JJ
Bruin
J E
JE
Gerstein
H C
HC
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D002452:Cell Count; D003924:Diabetes Mellitus, Type 2 / Q000517:prevention & control*; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009538:Nicotine; D018722:Nicotinic Agonists; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D018722:Nicotinic Agonists; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009538:Nicotine