天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (11): 1221-1225.

• 专题研究-内分泌疾病 • 上一篇    下一篇

沙格列汀通过抑制 SDF-1 降解促进 2 型糖尿病大鼠胰岛β细胞增殖

邢云芝， 李春君， 丁敏， 于倩， 于德民△   

  1. 天津医科大学代谢病医院， 卫生部激素与发育重点实验室 （邮编 300070）
  • 收稿日期:2015-09-15 修回日期:2015-10-23 出版日期:2015-11-15 发布日期:2015-11-15
  • 通讯作者: 于德民 E-mail:yudemintij@126.com E-mail:yudemintij@126.com
  • 作者简介:邢云芝 （1990）， 女， 医师， 硕士研究生， 主要从事糖尿病及其并发症研究

The protective effects of saxagliptin on β-cell proliferation by inhibiting the degradation of SDF-1 in type 2 diabetes rats#br#

XING Yunzhi, LI Chunjun, DING Min, YU Qian, YU Demin△#br#   

  1. Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University /Ministry of Health Key Laboratory of Hormones and Development, Tianjin 300070, China
  • Received:2015-09-15 Revised:2015-10-23 Published:2015-11-15 Online:2015-11-15
  • Contact: YU Demin E-mail:yudemintij@126.com E-mail:yudemintij@126.com

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摘要： 目的 探讨二肽基肽酶Ⅳ(DPP-4)抑制剂沙格列汀促进糖尿病大鼠胰岛β细胞增殖的相关机制。方法 将 SD 大鼠随机分为对照 （NC） 组 （n=10）、 糖尿病(DM)组 （n=10） 和沙格列汀治疗(DM-S)组 （n=10）。DM-S 组给予沙格列汀 1 mg/ （kg·d）灌胃 12 周。高糖钳夹法测胰岛功能， 免疫荧光双染观察胰腺组织中α细胞、 β细胞及 DPP-4、 基质细胞生成因子（SDF） -1 的表达， PCNA 免疫染色观察胰岛β细胞增殖， Western Blot 法检测丝氨酸苏氨酸蛋白激酶
(Akt)、 p-Akt、 β-catenin 及 free-β-catenin 的表达， Real Time-PCR 法检测基因 c-myc 及 cyclinD1 的表达。结果 与NC 组相比， DM 组大鼠血糖明显升高， 胰岛分泌功能明显受损， 胰岛β细胞明显减少。与 DM 组相比， 沙格列汀明显抑制 DPP-4 表达， 减少 SDF-1 降解， 增加胰岛β细胞增殖， 改善胰岛功能及病理学损害。结论 DPP-4 抑制剂沙格列汀能够明显改善胰岛功能， 其机制与抑制胰腺组织 DPP-4 表达， 减少 SDF-1 降解， 促进胰岛β细胞增殖有关。

关键词: 二肽基肽酶Ⅳ抑制剂, 糖尿病, 2 型, 细胞增殖, 胰岛β细胞, 基质细胞生成因子

Abstract: Objective To investigate the mechanism of a dipeptidyl-peptidase-4 (DPP-4) inhibitor, saxagliptin, promoting the regeneration of islet beta cells in diabetic rats.  Methods The male SD rats were randomly divided into three groups including control group (NC, n=10), diabetes group (DM, n=10) and diabetes treated with saxagliptin group (DM-S, n=10). DM-S group was treated with saxagliptin 1 mg/(kg·d) for twelve weeks. The pancreatic β cell function was analysed by hyperglycemic clamps. Immunohistochemistry with anti-PCNA was performed to observe the proliferation rate of pancreatic β cells. Immunofluorescence double staining with anti-insulin, anti-glucagon, anti-DPP-4 and anti-SDF-1 were performed to observe the expression of insulin, glucagon, DPP-4 and SDF-1 in pancreatic tissue. Western blot assay was performed to test the expression of Akt, p-Akt, β-catenin and free-β-catenin protein, and RT-PCR was performed to test the expression  levels of c-myc and cyclinD1 mRNA in pancreatic tissue. Results Compared with NC group, there were significantly increased blood glucose, decreased islet function and β cell mass in DM group. Compared with DM rats, saxagliptin treatment significantly inhibited the expression of DPP-4, decreased the degradation of SDF-1, stimulated the proliferation of β cells, and ultimately improved the islet function and histopathological changes of pancreas. Conclusion DPP-4 inhibitor saxagliptin can significantly improve islet function, which involved in the inhibition of the expression of DPP- 4, the decreased degradation of SDF-1 and the stimulation of the proliferation of β cells.

Key words: dipeptidyl-peptidase Ⅳ inhibitors, diabetes mellitus, type 2, cell proliferation, islet beta cell, stromal cell derived factor