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Obesity is found to be a significant risk factor for type 2 diabetes mellitus (T2DM), attributed to lipotoxicity-induced β-cell dysfunction. However, the specific mechanism involved in the process remains incompletely unclarified. The current study demonstrated lipotoxicity resulted in the activation of ER stress, which increased the protein level of TXNIP, thereby inducing senescence-assiciated dysfunction in MIN6 cells under high fat environment. And we also found sesamol, a natural functional component extracted from sesame, was able to alleviate senescence-associated β-cell dysfunction induced by lipotoxicity by inhibiting ER stress and TXNIP. Our findings provided novel insights into senescence-related T2DM and propose innovative therapeutic approaches for utilizing sesamol in the treatment of T2DM in the obese elderly population.
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http://dx.doi.org/10.1002/jbt.70038 | DOI Listing |
Mol Nutr Food Res
September 2025
Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
Current research indicates that insulin secretion deficiency in β-cells contributes to Type 2 diabetes mellitus (T2DM), which is associated with neuropeptide Y receptor (Npy1r) overexpression from neuropeptide Y (NPY) system dysregulation. To date, limited literature has explored nobiletin (NOB) as a circadian modulator for restoring β-cell function through Npy1r regulation. This study investigates NOB's stimulatory effects on insulin secretion via Npy1r and clock-modulatory signaling to elucidate its underlying mechanism.
View Article and Find Full Text PDFToxics
July 2025
Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China.
(1) Background: Epidemiological studies link ozone (O) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.
View Article and Find Full Text PDFBiol Trace Elem Res
June 2025
College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
Abnormal iron metabolism can cause β-cell dysfunction, and dedifferentiation is the core mechanism of β-cell dysfunction. However, the specific role of abnormal iron metabolism in dedifferentiation remains unclear. Forkhead Box O1 (FoxO1) is a crucial regulator of iron metabolism and dedifferentiation, and its transcriptional activity is regulated by silent information regulator 1 (SIRT1).
View Article and Find Full Text PDFWorld J Diabetes
May 2025
Department of Endocrinology, The Affiliated Dazu's Hospital of Chongqing Medical University, The People's Hospital of Dazu, Chongqing 402360, China.
Background: Type 2 diabetes mellitus (T2DM) is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications, posing a substantial health burden. Although therapies, such as GLP-1 receptor agonists and SGLT2 inhibitors, have been successfully developed, new therapeutic options are still expected to offer better blood glucose control and decrease complications.
Aim: To elucidate the mechanism by which TERT/FOXO1 affects high glucose (HG)-induced dysfunction in islet β-cells the regulation of ATG9A-mediated autophagy.
J Diabetes
June 2025
Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, Shanghai, China.
Background: Pancreatic β-cells function deteriorates during aging, leading to increased risk of type 2 diabetes. We and others previously demonstrated that p53 activation triggers β-cell senescence and dysfunction in aging, but how its activity is controlled remains incompletely understood. Metabolites are not only by-products of metabolic pathways but also function as messengers to regulate various biological pathways.
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