- 作者：Hiroyo Ota ; Asako Itaya-Hironaka ; Akiyo Yamauchi ; Sumiyo Sakuramoto-Tsuchida ; Tomoko Miyaoka ; Takanori Fujimura ; Hiroki Tsujinaka ; Kiyomi Yoshimoto ; Kan-ichi Nakagawara ; Shinji Tamaki ; Shin Takasawa ; Hiroshi Kimura
- 关键词：Apoptosis ; Hepatocyte growth factor ; Interleukin-6 ; Intermittent hypoxia ; Pancreatic ¦Â cell proliferation ; Regenerating gene ; Sleep apnea syndrome
- 刊名：Life Sciences
- 出版年：2013
- 出版时间：4 November, 2013
- 年：2013
- 卷：93
- 期：18-19
- 页码：664-672
- 全文大小：600 K
Aims
Although accumulating evidence suggests the associations between sleep apnea syndrome (SAS) and type 2 diabetes, the direct effect of intermittent hypoxia (IH) on pancreatic ¦Â cell proliferation remains a missing piece of the puzzle.Main methods
Rat RINm5F ¦Â cells, hamster HIT-T15 ¦Â cells, and human 1.1B4 ¦Â cells were exposed to normoxia (21 % O2, 5 % CO2, and balance N2), to sustained hypoxia (SH: 1 % O2, 5 % CO2, and balance N2), or to intermittent hypoxia (IH: 64 cycles of 5 min SH and 10 min normoxia) for 24 h. After the treatment, cellular proliferation and apoptosis were measured by WST-8 assay and TUNEL method, respectively. The expression of regenerating gene (Reg) family, interleukin (IL)-6, and hepatocyte growth factor (HGF) was determined by real-time RT-PCR.
Key findings
The cellular proliferation of HIT-T15, RINm5F and 1.1B4 cells by IH was significantly increased, whereas apoptosis of these cells was unchanged. Real-time RT-PCR revealed that the mRNA levels of Reg family genes, IL-6, a typical Reg family gene inducer, and HGF, an inhibitor of high-concentration of Reg protein-induced apoptosis, were increased in IH-treated cells. In addition, siRNAs against rat Reg family genes except for PAP I/Reg 2 attenuated IH-induced ¦Â cell proliferation.
Significance
IH stress stimulates pancreatic ¦Â cell to induce IL-6 gene expression. By the IL-6 stimulation, ¦Â cells over-express Reg family genes as well as HGF gene. Reg family proteins stimulate ¦Â cell proliferation and HGF inhibits apoptosis of ¦Â cells. As a result, ¦Â cell numbers are increased by IH.