Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails Markers of β-Cell Dedifferentiation in db/db Mice.
Pair Feeding, but Not Insulin, Phloridzin, or Rosiglitazone Treatment, Curtails Markers of β-Cell Dedifferentiation in db/db Mice.
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作者：
Ishida E;Kim-Muller JY;Accili D
β-细胞衰竭是2型糖尿病的标志。在细胞功能障碍的几种细胞生物学机制中，我们和其他人最近提出β细胞的去分化可以解释β细胞衰竭的缓慢进行性发作和部分可逆性。因此，我们在胰岛素抵抗型糖尿病的人类和实验动物模型中提供了这种过程的证据。在这项研究中，我们询问β细胞去分化是否可以通过饮食或药物治疗糖尿病来预防。db/db小鼠是一种广泛使用的胰岛素抵抗型糖尿病和肥胖模型，它们被成对喂养或用Sglt抑制剂phloridzin、胰岛素增敏剂罗格列酮或胰岛素治疗。所有治疗方法在降低血糖水平方面都同样有效。配对喂养和苯丙嗪也能显著减轻体重。然而，通过Foxo1和Aldh1a3免疫组化评估，四种处理之间的配对喂养导致β细胞去分化减少。饮食在一定程度上恢复β细胞功能的作用与人类糖尿病的数据一致，并提供了生活方式改变作为有效干预糖尿病进展的另一种潜在机制。
β-Cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of β-cells can explain the slowly progressive onset and partial reversibility of β-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether β-cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes. db/db mice, a widely used model of insulin-resistant diabetes and obesity, were either pair fed or treated with the Sglt inhibitor phloridzin, the insulin-sensitizer rosiglitazone, or insulin. All treatments were equally efficacious in reducing plasma glucose levels. Pair feeding and phloridzin also resulted in significant weight loss. However, pair feeding among the four treatments resulted in a reduction of β-cell dedifferentiation, as assessed by Foxo1 and Aldh1a3 immunohistochemistry. The effect of diet to partly restore β-cell function is consistent with data in human diabetes and provides another potential mechanism by which lifestyle changes act as an effective intervention against diabetes progression.
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