详细记录  
题名:Pancreatic beta cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene.
作者:OTA H; ITAYA-HIRONAKA A; YAMAUCHI A; SAKURAMOTO-TSUCHIDA S; MIYAOKA T; FUJIMURA T; TSUJINAKA H; YOSHIMOTO K; NAKAGAWARA K; TAMAKI S; TAKASAWA S; KIMURA H;
来源:Life Sci. 2013 Nov 4;93(18-19):664-72. doi: 10.1016/j.lfs.2013.09.001. Epub 2013 [ IF= 0.00 ] ]
URL :10.1016/j.lfs.2013.09.001
日期:20131203
摘要: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 beta cell proliferation remains a missing piece of the
puzzle. MAIN METHODS: Rat RINm5F beta cells, hamster HIT-T15 beta cells, and
human 1.1B4 beta 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 beta cell proliferation. SIGNIFICANCE: IH stress stimulates
pancreatic beta cell to induce IL-6 gene expression. By the IL-6 stimulation,
beta cells over-express Reg family genes as well as HGF gene. Reg family proteins
stimulate beta cell proliferation and HGF inhibits apoptosis of beta cells. As a
result, beta cell numbers are increased by IH.

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