Effect of combining rosiglitazone with either metformin or insulin on β-cell mass and function in an animal model of Type 2 diabetes characterized by reduced β-cell mass at birth


Alison C. Holloway, Department of Obstetrics and Gynecology, McMaster University, Rm 3N52 HSC, 1200 Main Street W., Hamilton, ON L8N 3Z5, Canada.
Tel: +1 905 525 9140 ext. 22130
Fax: +1 905 524 2911
Email: hollow@mcmaster.ca


Background:  Interventions that preserve or increase β-cell mass may also prevent Type 2 diabetes. Rosiglitazone alone, as well as in combination with metformin, prevents diabetes in people with high, yet non-diabetic glucose levels. These effects may be mediated through changes in β-cell mass. In the present study, the effect of combining rosiglitazone with metformin and/or insulin on β-cell mass and glucose levels was examined in a rat model of Type 2 diabetes.

Methods:  Diabetes-prone pups were randomized to receive rosiglitazone alone or in combination with metformin and/or insulin starting at 4 weeks of age. β-Cell mass and glucose homeostasis were examined in adulthood.

Results:  Rosiglitazone treatment reduced insulin resistance and partially restored β-cell mass in animals with reduced β-cell mass at birth. The addition of metformin to rosiglitazone decreased insulin resistance and reduced weight gain, but had no additional effect on β-cell mass. Conversely, the addition of insulin had no additional effect on these outcomes. Although the combination of rosiglitazone and metformin did not affect β-cell mass at 26 weeks of age, it did result in reduced body weight and insulin resistance.

Conclusion:  The results of the present study suggest that the addition of metformin to rosiglitazone improves the metabolic profile through an effect on insulin resistance and not β-cell mass.