Li EnXu, Nakata Masanori, Shinozaki Atsumi, Yang Yifei, Zhang Boyang, Yada Toshihiko
Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke 329-0498, Japan.
Endocr J. 2016 Jul 30;63(7):611-9. doi: 10.1507/endocrj.EJ16-0164. Epub 2016 Apr 19.
Regeneration of pancreatic β-cell mass benefits both type 1 and type 2 diabetic patients. A recent study identified betatrophin as a β-cell proliferation factor. However, the expressional regulation of betatrophin remains less defined. In this study, we aimed to clarify the regulation of betatrophin expression in obese type 2 vs. type 1 diabetes model animals. We experimented type 2 diabetes models, diet-induced-obesity (DIO) mice and db/db mice, and type 1 diabetes models, C57B6 mice receiving streptozotocin (STZ) or 70% pancreatectomy to destroy or remove β-cells. Serum betatrophin levels and betatrophin mRNA expressions in the liver, white adipose tissue (WAT) and brown adipose tissue (BAT) were measured. In DIO mice and db/db mice, serum betatrophin and betatrophin mRNA expressions in the liver, WAT and BAT were elevated in parallel with increases in body weight and plasma insulin. These elevated betatrophin mRNA expressions were not altered by treatment with SGLT2 inhibitor that ameliorated hyperglycemia. In pancreatectomized mice, betatrophin expression in WAT decreased in parallel with reductions in weight and insulin. In STZ-treated mice, betatrophin expressions in the liver, WAT and BAT were reduced. However, when the mouse liver slices were cultured with STZ, betatrophin expression was significantly reduced, indicating a direct action of STZ on the liver. These results indicate that the expression of betatrophin is upregulated in the liver, WAT and BAT in obese hyperinsulinemic type 2 diabetes but decreased in WAT in hypoinsulinemic type 1 diabetes, suggesting its positive correlation with body weight and plasma insulin but not blood glucose.
胰腺β细胞量的再生对1型和2型糖尿病患者均有益。最近的一项研究将β细胞营养因子确定为一种β细胞增殖因子。然而，β细胞营养因子的表达调控仍不太明确。在本研究中，我们旨在阐明肥胖2型与1型糖尿病模型动物中β细胞营养因子表达的调控情况。我们对2型糖尿病模型（饮食诱导肥胖（DIO）小鼠和db/db小鼠）以及1型糖尿病模型（接受链脲佐菌素（STZ）或70%胰腺切除术以破坏或去除β细胞的C57B6小鼠）进行了实验。测量了肝脏、白色脂肪组织（WAT）和棕色脂肪组织（BAT）中的血清β细胞营养因子水平以及β细胞营养因子mRNA表达。在DIO小鼠和db/db小鼠中，肝脏、WAT和BAT中的血清β细胞营养因子和β细胞营养因子mRNA表达随着体重和血浆胰岛素的增加而平行升高。这些升高的β细胞营养因子mRNA表达不会因使用改善高血糖的SGLT2抑制剂治疗而改变。在胰腺切除的小鼠中，WAT中的β细胞营养因子表达随着体重和胰岛素的降低而平行下降。在STZ处理的小鼠中，肝脏、WAT和BAT中的β细胞营养因子表达降低。然而，当用STZ培养小鼠肝脏切片时，β细胞营养因子表达显著降低，表明STZ对肝脏有直接作用。这些结果表明，β细胞营养因子的表达在肥胖高胰岛素血症2型糖尿病的肝脏、WAT和BAT中上调，但在低胰岛素血症1型糖尿病的WAT中降低，提示其与体重和血浆胰岛素呈正相关，而与血糖无关。
