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.
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.


CONCLUSIONS
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.
Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada. hollow@mcmaster.ca
Alison C
AC
Holloway
Bart P
BP
Hettinga
Hertzel C
HC
Gerstein
D050154:Adiposity / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin