Endoplasmic Reticulum (ER) Stress in Part Mediates Effects of Angiotensin II in Pancreatic Beta Cells

Figures

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  Figure 1. Dose and time-dependent effects of Angiotensin II. INS-1E cells were treated with different doses of Ang II to determine the optimal dose of Ang II to induce ER stress. (A and B) Ang II at all doses tested did not alter activated transcription factor 4 (Atf4) and C/EBP homologous protein (Chop) gene levels at 24 hours. (C) Ang II at 50 nM increased Atf4 gene levels, and (D) Ang II at all doses tested increased Chop gene levels at 48 hours. (E) Ang II only at 50 nm reduced insulin secretion at 24 hours. (F) Ang II at 50 nM reduced insulin secretion at 48 hours. Data are presented as mean ± SEM (n=4). *p< 0.05 compared to control.

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  Figure 2. Dose and time-dependent effects of Angiotensin II on Human Pancreatic islets. Human Pancreatic islets were treated with different doses of Ang II for 48 hours to determine the optimal dose of Ang II to induce ER stress. (A) Ang II at 50 nM increased gene levels of activated transcription factor 4 (Atf4). (B) Ang II at both 50 and 100 nM increased C/EBP homologous protein (Chop) gene levels. Data are presented as mean ± SEM (n=4). *p< 0.05 compared to control.

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  Figure 3. Captopril reduces ER stress. INS-1E cells treated with 100 µM captopril reduces ER stress as shown by (A) activated transcription factor 4 (Atf4) gene levels, (B) C/EBP homologous protein (Chop) expression gene levels and (C) improved insulin secretion. Data are presented as mean ± SEM (n=5 each group). *p< 0.05 compared to control. $p< 0.1.

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  Figure 4. Angiotensin receptor inhibitors reduce ER stress. INS-1E cells treated with telmisartan (T; AT1 inhibitor), P186 (P; AT2 inhibitor) reduce ER stress as shown by (A) activated transcription factor 4 (Atf4) gene levels, (B) C/EBP homologous protein (Chop) gene levels and (C) improved insulin secretion. Data are presented as mean ± SEM (n=4-5 each group). Means without the same letter are different.

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  Figure 5. ER stress inhibitor reduces ER stress even in the presence of Angiotensin II. INS-1E cells treated with Ang II and ER stress inhibitor, 4-phenyl butyric acid reduces ER stress as shown (A) activated transcription factor 4 (Atf4), (B) C/EBP homologous protein (Chop) and (C) improved insulin secretion. Data are presented as mean ± SEM (n=5 each group). *p< 0.05 compared to Ang II.

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  Figure 6. Angiotensin induces inflammation through iNos. INS-1E cells treated with telmisartan (T; AT1 inhibitor), P186 (P; AT2 inhibitor) reduce inflammation as shown by (A) inducible nitric oxide synthase (iNos) gene levels, (B) nuclear factor kappa-light-chain-enhancer of activated B cells (NfkB) gene levels and (C) tumor necrosis factor alpha (Tnf-α). Data are presented as mean ± SEM (n=5 each group). Means without the same letter are different.

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  Figure 7. Alterations in microRNAs associated with ER stress. INS-1E cells were treated with Ang II, and levels of different miRNAs were measured. (A) miR-30c was reduced while (B) miR-30a and (C) miR-708 was unaltered in the presence of Ang II. Data are presented as mean ± SEM (n=3). *p<0.05.