Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling
Dysregulated redox balance is involved in the pathogenesis of type 2 diabetes. While the benefit of antioxidants in neutralizing oxidative stress is well characterized, the potential harm of antioxidant-induced reductive stress is unclear. The aim of this study was to investigate the dose-dependent...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/6/2965 |
| _version_ | 1797470973998399488 |
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| author | Lital Argaev-Frenkel Tovit Rosenzweig |
| author_facet | Lital Argaev-Frenkel Tovit Rosenzweig |
| author_sort | Lital Argaev-Frenkel |
| collection | DOAJ |
| description | Dysregulated redox balance is involved in the pathogenesis of type 2 diabetes. While the benefit of antioxidants in neutralizing oxidative stress is well characterized, the potential harm of antioxidant-induced reductive stress is unclear. The aim of this study was to investigate the dose-dependent effects of the antioxidant N-acetylcysteine (NAC) on various tissues involved in the regulation of blood glucose and the mechanisms underlying its functions. H<sub>2</sub>O<sub>2</sub> was used as an oxidizing agent in order to compare the outcomes of oxidative and reductive stress on cellular function. Cellular death in pancreatic islets and diminished insulin secretion were facilitated by H<sub>2</sub>O<sub>2</sub>-induced oxidative stress but not by NAC. On the other hand, myotubes and adipocytes were negatively affected by NAC-induced reductive stress, as demonstrated by the impaired transmission of insulin signaling and glucose transport, as opposed to H<sub>2</sub>O<sub>2</sub>-stimulatory action. This was accompanied by redox balance alteration and thiol modifications of proteins. The NAC-induced deterioration of insulin signaling was also observed in healthy mice, while both insulin secretion and insulin signaling were improved in diabetic mice. This study establishes the tissue-specific effects of NAC and the importance of the delicate maintenance of redox balance, emphasizing the challenge of implementing antioxidant therapy in the clinic. |
| first_indexed | 2024-03-09T19:43:00Z |
| format | Article |
| id | doaj.art-054875cae0ba473a81965922d5b0c4ec |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T19:43:00Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-054875cae0ba473a81965922d5b0c4ec2023-11-24T01:29:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01236296510.3390/ijms23062965Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin SignalingLital Argaev-Frenkel0Tovit Rosenzweig1Department of Molecular Biology, Ariel University, Ariel 4070000, IsraelDepartment of Molecular Biology, Ariel University, Ariel 4070000, IsraelDysregulated redox balance is involved in the pathogenesis of type 2 diabetes. While the benefit of antioxidants in neutralizing oxidative stress is well characterized, the potential harm of antioxidant-induced reductive stress is unclear. The aim of this study was to investigate the dose-dependent effects of the antioxidant N-acetylcysteine (NAC) on various tissues involved in the regulation of blood glucose and the mechanisms underlying its functions. H<sub>2</sub>O<sub>2</sub> was used as an oxidizing agent in order to compare the outcomes of oxidative and reductive stress on cellular function. Cellular death in pancreatic islets and diminished insulin secretion were facilitated by H<sub>2</sub>O<sub>2</sub>-induced oxidative stress but not by NAC. On the other hand, myotubes and adipocytes were negatively affected by NAC-induced reductive stress, as demonstrated by the impaired transmission of insulin signaling and glucose transport, as opposed to H<sub>2</sub>O<sub>2</sub>-stimulatory action. This was accompanied by redox balance alteration and thiol modifications of proteins. The NAC-induced deterioration of insulin signaling was also observed in healthy mice, while both insulin secretion and insulin signaling were improved in diabetic mice. This study establishes the tissue-specific effects of NAC and the importance of the delicate maintenance of redox balance, emphasizing the challenge of implementing antioxidant therapy in the clinic.https://www.mdpi.com/1422-0067/23/6/2965type 2 diabetesN-acetylcysteineredox balanceglucose uptakeglutathionylationoxidative stress |
| spellingShingle | Lital Argaev-Frenkel Tovit Rosenzweig Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling International Journal of Molecular Sciences type 2 diabetes N-acetylcysteine redox balance glucose uptake glutathionylation oxidative stress |
| title | Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling |
| title_full | Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling |
| title_fullStr | Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling |
| title_full_unstemmed | Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling |
| title_short | Complexity of NAC Action as an Antidiabetic Agent: Opposing Effects of Oxidative and Reductive Stress on Insulin Secretion and Insulin Signaling |
| title_sort | complexity of nac action as an antidiabetic agent opposing effects of oxidative and reductive stress on insulin secretion and insulin signaling |
| topic | type 2 diabetes N-acetylcysteine redox balance glucose uptake glutathionylation oxidative stress |
| url | https://www.mdpi.com/1422-0067/23/6/2965 |
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