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Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells.

Shi X, Deng H, Dai Z, Xu Y, Xiong X, Ma P, Cheng J - Oxid Med Cell Longev (2015)

Bottom Line: At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress.Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2.Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

ABSTRACT
Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

No MeSH data available.


Related in: MedlinePlus

Nr2e1 silencing exaggerates lipotoxicity-induced beta cell dysfunction. (a) Insulin secretion in response to 2.5 and 20 mM glucose in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells preincubated during 48 h with or without 0.5 mM palmitate. Results are means ± SD of 3 independent experiments. ∗P < 0.05 compared to MIN6-shc in 2.5 mM glucose. #P < 0.05 compared to MIN6-shc in 20 mM glucose. (b) Insulin mRNA levels of MIN6-shc, MIN6-sh2, and MIN6-sh3 cells incubated during 48 h with or without 0.5 mM palmitate. Data represent means ± SD of three observations. ∗P < 0.05 compared to MIN6-shc incubated with palmitate.
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fig5: Nr2e1 silencing exaggerates lipotoxicity-induced beta cell dysfunction. (a) Insulin secretion in response to 2.5 and 20 mM glucose in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells preincubated during 48 h with or without 0.5 mM palmitate. Results are means ± SD of 3 independent experiments. ∗P < 0.05 compared to MIN6-shc in 2.5 mM glucose. #P < 0.05 compared to MIN6-shc in 20 mM glucose. (b) Insulin mRNA levels of MIN6-shc, MIN6-sh2, and MIN6-sh3 cells incubated during 48 h with or without 0.5 mM palmitate. Data represent means ± SD of three observations. ∗P < 0.05 compared to MIN6-shc incubated with palmitate.

Mentions: To explore the potential impact of Nr2e1 deficiency in beta cell function, GSIS was measured in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells. In normal conditions, Nr2e1 downregulation in MIN6 cells did not affect the dose-response to glucose (Figure 5(a)). Also the insulin mRNA levels did not differ between control and Nr2e1 silenced cells (Figure 5(b)). So we next tested whether Nr2e1 alters GSIS in lipotoxic conditions. As expected, treatment with 0.5 mM palmitate for 48 h impaired GSIS and reduced mRNA level of insulin in MIN6 cells. These effects were more obvious in Nr2e1 silenced cells (Figures 5(a) and 5(b)).


Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells.

Shi X, Deng H, Dai Z, Xu Y, Xiong X, Ma P, Cheng J - Oxid Med Cell Longev (2015)

Nr2e1 silencing exaggerates lipotoxicity-induced beta cell dysfunction. (a) Insulin secretion in response to 2.5 and 20 mM glucose in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells preincubated during 48 h with or without 0.5 mM palmitate. Results are means ± SD of 3 independent experiments. ∗P < 0.05 compared to MIN6-shc in 2.5 mM glucose. #P < 0.05 compared to MIN6-shc in 20 mM glucose. (b) Insulin mRNA levels of MIN6-shc, MIN6-sh2, and MIN6-sh3 cells incubated during 48 h with or without 0.5 mM palmitate. Data represent means ± SD of three observations. ∗P < 0.05 compared to MIN6-shc incubated with palmitate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Nr2e1 silencing exaggerates lipotoxicity-induced beta cell dysfunction. (a) Insulin secretion in response to 2.5 and 20 mM glucose in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells preincubated during 48 h with or without 0.5 mM palmitate. Results are means ± SD of 3 independent experiments. ∗P < 0.05 compared to MIN6-shc in 2.5 mM glucose. #P < 0.05 compared to MIN6-shc in 20 mM glucose. (b) Insulin mRNA levels of MIN6-shc, MIN6-sh2, and MIN6-sh3 cells incubated during 48 h with or without 0.5 mM palmitate. Data represent means ± SD of three observations. ∗P < 0.05 compared to MIN6-shc incubated with palmitate.
Mentions: To explore the potential impact of Nr2e1 deficiency in beta cell function, GSIS was measured in MIN6-shc, MIN6-sh2, and MIN6-sh3 cells. In normal conditions, Nr2e1 downregulation in MIN6 cells did not affect the dose-response to glucose (Figure 5(a)). Also the insulin mRNA levels did not differ between control and Nr2e1 silenced cells (Figure 5(b)). So we next tested whether Nr2e1 alters GSIS in lipotoxic conditions. As expected, treatment with 0.5 mM palmitate for 48 h impaired GSIS and reduced mRNA level of insulin in MIN6 cells. These effects were more obvious in Nr2e1 silenced cells (Figures 5(a) and 5(b)).

Bottom Line: At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress.Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2.Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

ABSTRACT
Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.

No MeSH data available.


Related in: MedlinePlus