Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada.
J Diabetes. 2011 Mar;3(1):74-81. doi: 10.1111/j.1753-0407.2010.00101.x.
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.
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.
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.
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.
干预β细胞质量的保存或增加也可能预防 2 型糖尿病。罗格列酮单独使用，以及与二甲双胍联合使用，可预防高血糖但尚未达到糖尿病水平的人群发生糖尿病。这些作用可能是通过β细胞质量的变化介导的。在本研究中，我们在 2 型糖尿病大鼠模型中研究了将罗格列酮与二甲双胍和/或胰岛素联合使用对β细胞质量和血糖水平的影响。
将易患糖尿病的幼崽随机分为 4 周龄开始接受罗格列酮单独治疗或与二甲双胍和/或胰岛素联合治疗。在成年期检查β细胞质量和葡萄糖稳态。
罗格列酮治疗可降低胰岛素抵抗，并部分恢复出生时β细胞质量减少的动物的β细胞质量。二甲双胍联合罗格列酮可降低胰岛素抵抗和体重增加，但对β细胞质量无额外影响。相反，胰岛素的添加对这些结果没有额外的影响。尽管罗格列酮和二甲双胍联合使用对 26 周龄时的β细胞质量没有影响，但它确实导致体重减轻和胰岛素抵抗降低。
本研究的结果表明，二甲双胍联合罗格列酮通过影响胰岛素抵抗而不是β细胞质量来改善代谢谱。
