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

Ota, Hiroyo; Itaya‐Hironaka, Asako; Yamauchi, Akiyo; Sakuramoto‐Tsuchida, Sumiyo; Miyaoka, Tomoko; Fujimura, Taku; Tsujinaka, Hiroki; Yoshimoto, Kiyomi; Nakagawara, Kan-ichi; Tamaki, Shinji; Takasawa, Shin; Kimura, Hiroshi

doi:10.1016/j.lfs.2013.09.001

Cited by 52 publications

(104 citation statements)

References 59 publications

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“…To determine whether IH decreases apoptosis, we next measured apoptosis of RINm5F and HIT-T15 cells by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) method, and found no statistically significant difference in apoptosis between normoxia-and IH-treated β cells. These results indicate that IH directly increases β cell proliferation [18]. The results were well fitted the results that pancreatic β cell proliferation in vivo mouse model of intermittent hypoxia [15].…”

Section: Increases In β Cell Proliferation By Ihsupporting

confidence: 85%

“…In order to evaluate independent Reg family members, we introduced small interfering RNAs (siRNAs) for rat Reg mRNAs into RINm5F β cells and measured IH-induced cell proliferation by WST-8 assay. We found that the introduction of siRNAs for Reg I, PAP II/Reg III, PAP III, and Reg IV suppressed IH-induced β cell proliferation, whereas siRNA for PAP I/Reg2 did not change the cell numbers [18], indicating the involvement of Reg family genes, at least Reg I, PAP II/Reg III, PAP III, and Reg IV in rat, in IH-induced pancreatic β cell proliferation.…”

Section: Reg Family Gene Expression By Ihmentioning

confidence: 79%

“…We analyzed the mRNA levels of Reg family genes by real-time RT-PCR and found that the mRNA levels of Reg I, PAP II/Reg III, PAP III, and Reg IV significantly increased in rat RINm5F β cells by IH stimulation. The mRNA level of REG Iα was significantly increased in human 1.1B4 β cells by IH [18]. In order to evaluate independent Reg family members, we introduced small interfering RNAs (siRNAs) for rat Reg mRNAs into RINm5F β cells and measured IH-induced cell proliferation by WST-8 assay.…”

Section: Reg Family Gene Expression By Ihmentioning

confidence: 99%

“…We then determined IL-6 mRNA expression in RINm5F and 1.1B4 β cells exposed to IH and found that the mRNA levels of IL-6 in RINm5F and 1.1B4 cells were significantly increased by IH [18], suggesting that IH stimulation upregulates Reg family mRNAs through IL-6 expression in pancreatic β cells. Recently, up-regulation of IL-6 in pancreatic islets of in vivo mouse IH model was also reported [21].…”

Section: Increased Expression Of Interleukin (Il)-6 Gene By Ihmentioning

confidence: 99%

“…In a mouse model, IH was found to cause β cell replication without hyperglycemia [15,16], suggesting a possible mechanism that IH directly stimulates β cell replication. Here, we focus on the impact of IH on pancreatic β cells, particularly β cell dysfunction and proliferation, using an in vitro IH system [17,18].…”

Section: Introductionmentioning

confidence: 99%

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Intermittent Hypoxia in Pancreatic beta Cells

Ota¹,

Takasawa²,

Yamauchi³

et al. 2015

Pancreat Disord Ther

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Sleep apnea syndrome (SAS) a highly prevalent disorder, and characterized by repetitive episodes of intermittent hypoxia (IH), i.e. recurrent episodes of oxygen desaturation during sleep, the development of daytime sleepiness, and deterioration in the quality of life. Multiple epidemiological studies have provided evidence implicating the presence of SAS as a risk factor for insulin resistance and type 2 diabetes and have reported that type 2 diabetes is associated with SAS independently of age, sex, and body habitus. One of the postulated mechanisms for the metabolic alterations associated with SAS is that IH leads to substantial alterations in both pancreatic β cell function and organ glucose homeostasis. On the other hand, hyperglycemia is known to increase the rate of β cell replication, which can provide an increased source of insulin to combat insulin resistance. Although accumulating evidence suggests associations between SAS and type 2 diabetes, the direct effect of IH on pancreatic β cell has been unknown. In this review, we focus on the impact of IH on pancreatic β cells, particularly β cell dysfunction and cell proliferation.

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Section: Increases In β Cell Proliferation By Ihsupporting

confidence: 85%

Section: Reg Family Gene Expression By Ihmentioning

confidence: 79%

Section: Reg Family Gene Expression By Ihmentioning

confidence: 99%

Section: Increased Expression Of Interleukin (Il)-6 Gene By Ihmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Intermittent Hypoxia in Pancreatic beta Cells

Ota¹,

Takasawa²,

Yamauchi³

et al. 2015

Pancreat Disord Ther

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Intermittent hypoxia‐induced epiregulin expression by IL‐6 production in human coronary artery smooth muscle cells

et al. 2018

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Patients with obstructive sleep apnea ( OSA ) experience repetitive episodes of desaturation and resaturation of blood oxygen (known as intermittent hypoxia or IH ), during sleep. We showed previously that IH induced excessive proliferation of rat vascular smooth muscle cells through upregulation of members of the epidermal growth factor family, especially epiregulin ( EREG ), and the erbB2 receptor. In this study, we exposed human coronary artery smooth muscle cells to IH and found that IH significantly increased the expression of EREG . IH increased the production of interleukin‐6 ( IL ‐6) in smooth muscle cells, and the addition of IL ‐6 induced EREG expression. Small interfering RNA for IL ‐6 or IL ‐6 receptor attenuated the IH ‐induced increase in EREG . IL ‐6 may play a pivotal role in EREG upregulation by IH and consequently OSA ‐related atherosclerosis.

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