ArticleInternational journal of endocrinology2015
Insulin Increases Sestrin 2 Content by Reducing Its Degradation through the PI 3 K/mTOR Signaling Pathway.
Article in International journal of endocrinology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- Sestrin2 in diabetes and diabetic complications.Frontiers in endocrinology · 2023Review
- The functions and roles of sestrins in regulating human diseases.Cellular & molecular biology letters · 2022Review
- Sestrins' Expression in the Liver Is Not Altered by Short-Term Calorie Restriction in Young and Old Rats.Gerontology · 2022Article
- Association between serum Sestrin2 level and diabetic peripheral neuropathy in type 2 diabetic patients.World journal of clinical cases · 2021Article
- Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study.BMC endocrine disorders · 2021Article
- Sestrins in Physiological Stress Responses.Annual review of physiology · 2021Review
- Sestrins: Darkhorse in the regulation of mitochondrial health and metabolism.Molecular biology reports · 2020Review
- Association of serum sestrin 2 and betatrophin with serum neutrophil gelatinase associated lipocalin levels in type 2 diabetic patients with diabetic nephropathy.Journal of diabetes and metabolic disorders · 2020Article
- Article
- Sestrin2: Its Potential Role and Regulatory Mechanism in Host Immune Response in Diseases.Frontiers in immunology · 2019Review
- RBX1-mediated ubiquitination of SESN2 promotes cell death upon prolonged mitochondrial damage in SH-SY5Y neuroblastoma cells.Molecular and cellular biochemistry · 2018Article
- Sestrin2 as a Novel Biomarker and Therapeutic Target for Various Diseases.Oxidative medicine and cellular longevity · 2017Review
- The potential of sestrins as therapeutic targets for diabetes.Expert opinion on therapeutic targets · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sestrin (SESN) is known as a cysteine sulfinic acid reductase. Recently, nonredox functions of SESN in metabolic regulation and antitumor property have been recognized. While mechanisms underlying the expression of SESN are not fully understood. Here we report that insulin markedly increased SESN2 level in HepG2 cells through mTOR activation. To determine whether insulin affects SESN2 degradation, we assessed SESN2 turnover by applying the protein synthesis inhibitor, cycloheximide (CHX), and found that following insulin treatment SESN2 protein levels were reduced significantly slower than non-insulin-treated cells. Furthermore, the proteasomal inhibitor, MG132, dramatically increased SESN2 protein and its ubiquitination level while in the presence of MG132 insulin did not further increase SESN2 content, suggesting that insulin increases SESN2 content mainly via inhibiting its proteasomal degradation. We then explored the potential feedback role of SESN2 in insulin signaling by SESN2 siRNA knockdown in HepG2 cells. Following SESN2 knockdown insulin-stimulated PKB phosphorylation was enhanced and accompanied by reduced PTEN content. Taken together, our study suggests that insulin upregulates SESN2 content via the PI3K/mTOR signaling pathway and this effect is attributed to decreased SESN2 degradation. Furthermore, SESN2 via modulating PTEN plays a negative feedback role in insulin signaling.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.