Tags

Type your tag names separated by a space and hit enter

Emulsified isoflurane protects beta cells against high glucose-induced apoptosis via inhibiting endoplasmic reticulum stress.
Ann Palliat Med. 2020 Jan; 9(1):90-97.AP

Abstract

BACKGROUND

Pancreatic beta cell damage induced by glucose toxicity is an important factor in type 2 diabetes mellitus (T2DM). It has become evident that endoplasmic reticulum stress (ERS)-induced apoptosis was contributed to beta cell dysfunction and insulin resistance. Our previous work showed that emulsified isoflurane (EIso) could alleviate ERS in lung reperfusion injury. This study aimed to elucidate whether EIso could alleviate apoptosis induced by glucose in rat islet RIN-m5F beta cells via inhibiting ERS.

METHODS

RIN-m5F cells were divided into five groups: the control group; the 0.1G group, cultured in 0.1M glucose for 24 h; the 0.3G group, cultured in 0.3M glucose for 24 h; the 0.3G + 57E group, cultured in 0.3M glucose with 57 µM EIso for 24 h, and the 0.3G + 76E group, cultured in 0.3M glucose with 76 µM EIso for 24 h. First, cell proliferation was measured by MTT assay, and the level of insulin secretion was measured with enzyme-linked immunosorbent assay (ELISA) kit. Second, the expression of B cell leukemia/lymphoma 2 (Bcl-2) associated X (Bax) and Bcl-2 were detected by Western blotting. The level of caspase-3 activity was assessed by colorimetric method. Finally, the ERS marker CHOP and GRP78 expression were detected by Western blotting. The levels of activating transcription factor-6 (ATF6), X-box-binding protein 1 (Xbp1), and eukaryotic translation initiation factor-2α (eIF2α) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) after being treated with EIso for 24 h.

RESULTS

We found that exposure to high glucose reduced RIN-m5F cell viability, stimulated the secretion of insulin, activated caspase-3, improved the expression of Bax, and down-regulated Bcl-2. EIso improved the survival and protected the function of RIN-m5F. Compared to the 0.3G group, treatment with EIso inhibited the activity of caspase-3, and decreased the expression of Bax. The expression of CHOP and GRP78 were significantly suppressed by EIso at 24 h in a dose-dependent manner. The level of ATF6, Xbp1, and eIF2α mRNA of RIN-m5F were enhanced by high glucose, but only eIF2α mRNA was significantly decreased by EIso treatment.

CONCLUSIONS

The present study suggests that high glucose induces rat islet beta cell RIN-m5F apoptosis and aggravates the function of beta cells. EIso protects beta cells against high glucose through the ERS-dependent apoptotic pathway and might serve as a potential therapy for diabetes.

Authors+Show Affiliations

Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China.Department of Anesthesiology, Wuxi Children's Hospital, Wuxi 214023, China.Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China.Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China.Department of Anesthesiology, Wuxi Children's Hospital, Wuxi 214023, China.Department of Medical Oncology, Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China.Department of Anesthesiology, Wuxi Children's Hospital, Wuxi 214023, China. wxdongwenyan@163.com.Center of Clinical Research, Wuxi People's Hospital of Nanjing Medical University, Wuxi 214023, China. sunjie0220@njmu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32005067

Citation

Yang, Zhenkun, et al. "Emulsified Isoflurane Protects Beta Cells Against High Glucose-induced Apoptosis Via Inhibiting Endoplasmic Reticulum Stress." Annals of Palliative Medicine, vol. 9, no. 1, 2020, pp. 90-97.
Yang Z, Wu S, Zhao J, et al. Emulsified isoflurane protects beta cells against high glucose-induced apoptosis via inhibiting endoplasmic reticulum stress. Ann Palliat Med. 2020;9(1):90-97.
Yang, Z., Wu, S., Zhao, J., Wang, Z., Yao, M., Lu, P., Dong, W., & Sun, J. (2020). Emulsified isoflurane protects beta cells against high glucose-induced apoptosis via inhibiting endoplasmic reticulum stress. Annals of Palliative Medicine, 9(1), 90-97. https://doi.org/10.21037/apm.2019.11.31
Yang Z, et al. Emulsified Isoflurane Protects Beta Cells Against High Glucose-induced Apoptosis Via Inhibiting Endoplasmic Reticulum Stress. Ann Palliat Med. 2020;9(1):90-97. PubMed PMID: 32005067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Emulsified isoflurane protects beta cells against high glucose-induced apoptosis via inhibiting endoplasmic reticulum stress. AU - Yang,Zhenkun, AU - Wu,Shuoxiong, AU - Zhao,Jingjing, AU - Wang,Zuoyu, AU - Yao,Min, AU - Lu,Peihua, AU - Dong,Wenyan, AU - Sun,Jie, PY - 2019/11/04/received PY - 2019/11/29/accepted PY - 2020/2/2/entrez PY - 2020/2/2/pubmed PY - 2020/10/28/medline KW - Emulsified isoflurane (EIso) KW - apoptosis KW - endoplasmic reticulum stress (ERS) KW - glucotoxicity KW - islet beta cell SP - 90 EP - 97 JF - Annals of palliative medicine JO - Ann Palliat Med VL - 9 IS - 1 N2 - BACKGROUND: Pancreatic beta cell damage induced by glucose toxicity is an important factor in type 2 diabetes mellitus (T2DM). It has become evident that endoplasmic reticulum stress (ERS)-induced apoptosis was contributed to beta cell dysfunction and insulin resistance. Our previous work showed that emulsified isoflurane (EIso) could alleviate ERS in lung reperfusion injury. This study aimed to elucidate whether EIso could alleviate apoptosis induced by glucose in rat islet RIN-m5F beta cells via inhibiting ERS. METHODS: RIN-m5F cells were divided into five groups: the control group; the 0.1G group, cultured in 0.1M glucose for 24 h; the 0.3G group, cultured in 0.3M glucose for 24 h; the 0.3G + 57E group, cultured in 0.3M glucose with 57 µM EIso for 24 h, and the 0.3G + 76E group, cultured in 0.3M glucose with 76 µM EIso for 24 h. First, cell proliferation was measured by MTT assay, and the level of insulin secretion was measured with enzyme-linked immunosorbent assay (ELISA) kit. Second, the expression of B cell leukemia/lymphoma 2 (Bcl-2) associated X (Bax) and Bcl-2 were detected by Western blotting. The level of caspase-3 activity was assessed by colorimetric method. Finally, the ERS marker CHOP and GRP78 expression were detected by Western blotting. The levels of activating transcription factor-6 (ATF6), X-box-binding protein 1 (Xbp1), and eukaryotic translation initiation factor-2α (eIF2α) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) after being treated with EIso for 24 h. RESULTS: We found that exposure to high glucose reduced RIN-m5F cell viability, stimulated the secretion of insulin, activated caspase-3, improved the expression of Bax, and down-regulated Bcl-2. EIso improved the survival and protected the function of RIN-m5F. Compared to the 0.3G group, treatment with EIso inhibited the activity of caspase-3, and decreased the expression of Bax. The expression of CHOP and GRP78 were significantly suppressed by EIso at 24 h in a dose-dependent manner. The level of ATF6, Xbp1, and eIF2α mRNA of RIN-m5F were enhanced by high glucose, but only eIF2α mRNA was significantly decreased by EIso treatment. CONCLUSIONS: The present study suggests that high glucose induces rat islet beta cell RIN-m5F apoptosis and aggravates the function of beta cells. EIso protects beta cells against high glucose through the ERS-dependent apoptotic pathway and might serve as a potential therapy for diabetes. SN - 2224-5839 UR - https://www.unboundmedicine.com/medline/citation/32005067/Emulsified_isoflurane_protects_beta_cells_against_high_glucose_induced_apoptosis_via_inhibiting_endoplasmic_reticulum_stress_ L2 - https://doi.org/10.21037/apm.2019.11.31 DB - PRIME DP - Unbound Medicine ER -