TY  - JOUR
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Mićanović, Dragica
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Savić, Nevena
AU  - Otašević, Vesna
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4910
AB  - The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.
PB  - London:Hindawi
T2  - Oxidative Medicine and Cellular Longevity
T1  - Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions
VL  - 2022
DO  - 10.1155/2022/3873420
SP  - 3873420
ER  - 

@article{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Mićanović, Dragica and Ivanović, Anđelija and Veličković, Ksenija and Savić, Nevena and Otašević, Vesna",
year = "2022",
abstract = "The main pathological hallmark of diabetes is the loss of functional β-cells. Among several types of β-cell death in diabetes, the
involvement of ferroptosis remains elusive. Therefore, we investigated the potential of diabetes-mimicking factors: high glucose
(HG), proinflammatory cytokines, hydrogen peroxide (H2O2), or diabetogenic agent streptozotocin (STZ) to induce ferroptosis
of β-cells in vitro. Furthermore, we tested the contribution of ferroptosis to injury of pancreatic islets in an STZ-induced
in vivo diabetic model. All in vitro treatments increased loss of Rin-5F cells along with the accumulation of reactive oxygen
species, lipid peroxides and iron, inactivation of NF-E2-related factor 2 (Nrf2), and decrease in glutathione peroxidase 4
expression and mitochondrial membrane potential (MMP). Ferrostatin 1 (Fer-1), ferroptosis inhibitor, diminished the abovestated effects and rescued cells from death in case of HG, STZ, and H2O2 treatments, while failed to increase MMP and to
attenuate cell death after the cytokines’ treatment. Moreover, Fer-1 protected pancreatic islets from STZ-induced injury in
diabetic in vivo model, since it decreased infiltration of macrophages and accumulation of lipid peroxides and increased the
population of insulin-positive cells. Such results revealed differences between diabetogenic stimuli in determining the destiny of
β-cells, emerging HG, H2O2, and STZ, but not cytokines, as contributing factors to ferroptosis and shed new light on an
antidiabetic strategy based on Nrf2 activation. Thus, targeting ferroptosis in diabetes might be a promising new approach for
preservation of the β-cell population. Our results obtained from in vivo study strongly justify this approach.",
publisher = "London:Hindawi",
journal = "Oxidative Medicine and Cellular Longevity",
title = "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions",
volume = "2022",
doi = "10.1155/2022/3873420",
pages = "3873420"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Mićanović, D., Ivanović, A., Veličković, K., Savić, N.,& Otašević, V.. (2022). Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity
London:Hindawi., 2022, 3873420.
https://doi.org/10.1155/2022/3873420

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Mićanović D, Ivanović A, Veličković K, Savić N, Otašević V. Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions. in Oxidative Medicine and Cellular Longevity. 2022;2022:3873420.
doi:10.1155/2022/3873420 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Mićanović, Dragica, Ivanović, Anđelija, Veličković, Ksenija, Savić, Nevena, Otašević, Vesna, "Ferroptosis as a Novel Determinant of β-Cell Death in Diabetic Conditions" in Oxidative Medicine and Cellular Longevity, 2022 (2022):3873420,
https://doi.org/10.1155/2022/3873420 . .

TY  - CONF
AU  - Stančić, Ana
AU  - Saksida, Tamara
AU  - Markelić, Milica
AU  - Vučetić, Milica
AU  - Grigorov, Ilijana
AU  - Martinović, Vesna
AU  - Ivanović, Anđelija
AU  - Veličković, Ksenija
AU  - Otašević, Vesna
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4899
AB  - Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.
PB  - Belgrade: Faculty of Chemistry: Serbian Biochemical Society
C3  - Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
T1  - Ferroptosis as a novel determinant of β-cell death in diabetic conditions
SP  - 146
EP  - 147
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4899
ER  - 

@conference{
author = "Stančić, Ana and Saksida, Tamara and Markelić, Milica and Vučetić, Milica and Grigorov, Ilijana and Martinović, Vesna and Ivanović, Anđelija and Veličković, Ksenija and Otašević, Vesna",
year = "2021",
abstract = "Diabetes is a complex metabolic disorder which incidence rises in the epidemic fashion, suggesting the urgent need for new therapies. Its main pathological hallmark is loss of functional β-cells, and to date, several types of β-cell death have been described – necrosis, apoptosis, and autophagy. However, the role of ferroptosis in reducing β-cell population in diabetes remains elusive. In this study we aimed to examine whether and how this type of cell death is implicated in regulation of β-cell destiny in diabetes. For that purpose, Rin-5F insulin-producing pancreatic cells were treated with diabetes-mimicking factors – high glucose (HG) and H2O2, as well with commonly used diabetogenic agent streptozotocin (STZ). Results showed that HG, H2O2 and STZ induce the death of Rin-5F cells along with the accumulation of reactive oxygen species, lipid peroxides and iron; inactivation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and decrease in glutathione peroxidase 4 expression. This is consistent with the effect of the treatment with RSL-3, a well-known inducer of ferroptosis. Ferrostatin-1, a ferroptosis inhibitor, diminished above-stated effects and rescued cells from death. Our data revealed that β-cells underwent ferroptotic cell death under diabetogenic conditions. Results also implicate HG and H2O2 as contributing factors to ferroptosis of β-cells and suggest the novel mechanism of STZ diabetogenic action. Furthermore, the results shed a new light on antidiabetic strategy based on Nrf2 activation, putting it into the anti-ferroptotic context. In close, targeting ferroptosis in diabetes might be a new promising therapeutic approach based on preservation of β-cell population.",
publisher = "Belgrade: Faculty of Chemistry: Serbian Biochemical Society",
journal = "Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia",
title = "Ferroptosis as a novel determinant of β-cell death in diabetic conditions",
pages = "146-147",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4899"
}

Stančić, A., Saksida, T., Markelić, M., Vučetić, M., Grigorov, I., Martinović, V., Ivanović, A., Veličković, K.,& Otašević, V.. (2021). Ferroptosis as a novel determinant of β-cell death in diabetic conditions. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia
Belgrade: Faculty of Chemistry: Serbian Biochemical Society., 146-147.
https://hdl.handle.net/21.15107/rcub_ibiss_4899

Stančić A, Saksida T, Markelić M, Vučetić M, Grigorov I, Martinović V, Ivanović A, Veličković K, Otašević V. Ferroptosis as a novel determinant of β-cell death in diabetic conditions. in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia. 2021;:146-147.
https://hdl.handle.net/21.15107/rcub_ibiss_4899 .

Stančić, Ana, Saksida, Tamara, Markelić, Milica, Vučetić, Milica, Grigorov, Ilijana, Martinović, Vesna, Ivanović, Anđelija, Veličković, Ksenija, Otašević, Vesna, "Ferroptosis as a novel determinant of β-cell death in diabetic conditions" in Serbian Biochemical Society Tenth Conference: with international participation: Biochemical Insights into Molecular Mechanisms; 2021 Sep 24; Kragujevac, Serbia (2021):146-147,
https://hdl.handle.net/21.15107/rcub_ibiss_4899 .