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Rosiglitazone prevents diabetes by increasing beta‐cell mass in an animal model of type 2 diabetes characterized by reduced beta‐cell mass at birth
Author(s) -
Holloway A. C.,
Petrik J. J.,
Bruin J. E.,
Gerstein H. C.
Publication year - 2008
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2007.00808.x
Subject(s) - rosiglitazone , endocrinology , medicine , offspring , diabetes mellitus , impaired glucose tolerance , type 2 diabetes , beta cell , glucose homeostasis , impaired fasting glucose , insulin resistance , pregnancy , biology , islet , genetics
Aim: 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.