RGD Reference Report - Pancreatic beta cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene. - Rat Genome Database

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Pancreatic beta cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene.

Authors: 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 
Citation: Ota H, etal., Life Sci. 2013 Nov 4;93(18-19):664-72. doi: 10.1016/j.lfs.2013.09.001. Epub 2013 Sep 17.
RGD ID: 9850134
Pubmed: PMID:24055447   (View Abstract at PubMed)
DOI: DOI:10.1016/j.lfs.2013.09.001   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of cell population proliferation  IMP 9850134pancreatic beta cellsRGD 
positive regulation of type B pancreatic cell proliferation  IMP 9850134 RGD 
response to hypoxia  IEP 9850134intermittent hypoxiaRGD 

Objects Annotated

Genes (Rattus norvegicus)
Reg1a  (regenerating family member 1 alpha)
Reg3b  (regenerating family member 3 beta)


Additional Information