Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep ob/ob mice.

Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep ob/ob mice.
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DOI:
10.1016/j.bbrc.2009.07.078
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发表时间:
2009-09
影响因子:
3.1
通讯作者:
Motohiro Sekiya;N. Yahagi;Y. Tamura;H. Okazaki;Masaki Igarashi;Keisuke Ohta;Mikio Takanashi;M. Kumagai;Satoru Takase;M. Nishi;Yoshinori Takeuchi;Y. Izumida;Midori Kubota;K. Ohashi;Y. Iizuka;H. Yagyu;T. Gotoda;R. Nagai;H. Shimano;N. Yamada;T. Kadowaki;S. Ishibashi;J. Osuga
Motohiro Sekiya;N. Yahagi;Y. Tamura;H. Okazaki;Masaki Igarashi;Keisuke Ohta;Mikio Takanashi;M. Kumagai;Satoru Takase;M. Nishi;Yoshinori Takeuchi;Y. Izumida;Midori Kubota;K. Ohashi;Y. Iizuka;H. Yagyu;T. Gotoda;R. Nagai;H. Shimano;N. Yamada;T. Kadowaki;S. Ishibashi;J. Osuga
中科院分区:
生物学4区
文献类型:
--
作者:
Motohiro Sekiya;N. Yahagi;Y. Tamura;H. Okazaki;Masaki Igarashi;Keisuke Ohta;Mikio Takanashi;M. Kumagai;Satoru Takase;M. Nishi;Yoshinori Takeuchi;Y. Izumida;Midori Kubota;K. Ohashi;Y. Iizuka;H. Yagyu;T. Gotoda;R. Nagai;H. Shimano;N. Yamada;T. Kadowaki;S. Ishibashi;J. Osuga

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胰岛素敏感脂肪酶(HSL)介导的胰岛β细胞脂解作用是否能通过改变脂毒性影响胰岛素分泌一直是一个有争议的问题。我们产生了缺乏瘦素和HSL的小鼠(Lepob/ob/HSL−/−),并探索了HSL在肥胖背景下胰腺β细胞中的作用。与进食状态下的Lepob/ob/HSL +/+相比,Lepob/ob/HSL −/−出现血糖水平升高和血浆胰岛素水平降低,而HSL缺乏不影响Lep+/+背景下的葡萄糖稳态。HSL的缺乏加剧了Lepob/obislets中甘油三酯的积累,导致葡萄糖刺激的胰岛素分泌减少。HSL的缺乏也减少了Lepob/ob小鼠的胰岛质量,由于细胞增殖减少。总之,HSL影响胰岛素分泌能力,特别是在肥胖的设置。
It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lepob/ob/HSL−/−) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lepob/ob/HSL−/−developed elevated blood glucose levels and reduced plasma insulin levels compared with Lepob/ob/HSL+/+in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep+/+background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lepob/obislets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lepob/obmice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.