Rosiglitazone prevents diabetes by increasing beta‐cell mass in an animal model of type 2 diabetes characterized by reduced beta‐cell mass at birth

Abstract

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. 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). 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. 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.