Taurine Alleviates Pancreatic β‐Cell Senescence by Inhibition of p53 Pathway DOI Creative Commons
Baomin Wang, Ziyan Wang, Yumei Yang

и другие.

Journal of Diabetes, Год журнала: 2025, Номер 17(6)

Опубликована: Июнь 1, 2025

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 dysfunction in but how its activity is controlled remains incompletely understood. Metabolites are not only by-products metabolic pathways also as messengers regulate various biological pathways. Taurine, a non-proteinogenic amino acid derived from cysteine, has anti-aging effects multiple cell types tissues. Nevertheless, role unclear. Untargeted metabolomic analysis was used determine differential metabolites pancreatic islets mice aging. In vitro, lines MIN6 INS-1E were treated with taurine transporter inhibitor, followed by measurement senescence-related markers. Multiple experimental techniques, such LC-MS/MS, co-immunoprecipitation, DARTS analysis, LiP-MS, study the mechanistic actions taurine. showed taurocholic significantly upregulated aged islets. Pretreatment inhibited naturally chemically induced senescent inflammatory program, oxidative stress, defective insulin secretion β-cells. SLC6A6 required mediate exogenous uptake, inhibition abolished anti-senescent Taurine bound CKDN2AIP interaction p53, thereby promoting degradation suppressing p53-dependent program. Our findings suggest increasing uptake might be feasible approach preserve targeting response.

Язык: Английский

The mitochondrial enzyme pyruvate carboxylase restricts pancreatic β-cell senescence by blocking p53 activation DOI Creative Commons
Yumei Yang, Baomin Wang,

Haoru Dong

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(44)

Опубликована: Окт. 22, 2024

Defective glucose-stimulated insulin secretion (GSIS) and β-cell senescence are hallmarks in diabetes. The mitochondrial enzyme pyruvate carboxylase (PC) has been shown to promote GSIS proliferation the clonal lines, yet its physiological relevance remains unknown. Here, we provide animal human data showing a role of PC protecting β-cells against maintaining under different pathological conditions. β-cell-specific deletion impaired induced mouse models either standard chow diet or prolonged high-fat feeding. Transcriptomic analysis indicated that p53-related cell cycle arrest activated PC-deficient islets. Overexpression inhibited hyperglycemia- aging-induced islets as well INS-1E β-cells, whereas knockdown provoked senescence. Mechanistically, interacted with MDM2 prevent degradation via binding motif, which turn restricts p53-dependent senescent program β-cells. On contrary, regulatory effects on tricarboxylic acid (TCA) anaplerotic flux p53-independent. We illuminate function controlling through MDM2–p53 axis.

Язык: Английский

Процитировано

3
Pyruvate Carboxylase as a Moonlighting Metabolic Enzyme Protects β‐Cell From Senescence DOI Creative Commons
Yumei Yang, Baomin Wang, Xiaomu Li

и другие.

Journal of Diabetes, Год журнала: 2025, Номер 17(2)

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway DOI Creative Commons
Lin Fan, Wenjing Yu, Ping Li

и другие.

Frontiers in Nutrition, Год журнала: 2025, Номер 12

Опубликована: Май 9, 2025

Background Mitochondrial oxidative damage in pancreatic β-cells is a key contributor to diabetes pathogenesis, particularly under hyperglycemic conditions. Polygonatum sibiricum polysaccharides (PSP) have demonstrated potential anti-diabetic effects; however, their precise mechanism, through the AMPK-SIRT1 pathway, remains unclear. Methods A diabetic zebrafish model was established by exposure 2% glucose for 28 days. Zebrafish were divided into control, model, low-dose PSP (50 μg/mL), medium-dose (100 high-dose (200 and metformin groups. Behavioral, biochemical, molecular analyses performed assess β-cell function, mitochondrial damage, inflammation. Network pharmacology analysis used predict targets, docking validated protein interactions. Immunofluorescence Western blotting (WB) conducted examine apoptosis-related expression. Results significantly improved swimming behavior, reduced blood fructosamine levels, enhanced ATP production ( p < 0.01). Antioxidant enzyme activities (SOD, CAT) increased, while stress markers (MDA) inflammatory cytokines (IL-1β, IL-6, TNF- α ) decreased treatment downregulated Cycs expression, alleviating damage. Moreover, upregulated AMPK SIRT1 expression 0.01), along with downstream regulators PGC-1α Nrf1/2 confirming pathway activation. identified 389 shared targets between diabetes-related pathways, implicating mechanisms of inflammation, insulin resistance, dysfunction. Molecular strong binding affinities SIRT1. WB showed cleaved caspase-3 levels apoptosis following Conclusion protects function mitigating via further highlight PSP’s as multi-target therapeutic agent diabetes.

Язык: Английский

Процитировано

0
Recent advances in small molecular inhibitors of pyruvate carboxylase for human diseases DOI
Weikai Guo,

Danyang Liu,

Ying Chen

и другие.

Bioorganic Chemistry, Год журнала: 2025, Номер unknown, С. 108658 - 108658

Опубликована: Июнь 1, 2025

Язык: Английский

Процитировано

0
Taurine Alleviates Pancreatic β‐Cell Senescence by Inhibition of p53 Pathway DOI Creative Commons
Baomin Wang, Ziyan Wang, Yumei Yang

и другие.

Journal of Diabetes, Год журнала: 2025, Номер 17(6)

Опубликована: Июнь 1, 2025

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 dysfunction in but how its activity is controlled remains incompletely understood. Metabolites are not only by-products metabolic pathways also as messengers regulate various biological pathways. Taurine, a non-proteinogenic amino acid derived from cysteine, has anti-aging effects multiple cell types tissues. Nevertheless, role unclear. Untargeted metabolomic analysis was used determine differential metabolites pancreatic islets mice aging. In vitro, lines MIN6 INS-1E were treated with taurine transporter inhibitor, followed by measurement senescence-related markers. Multiple experimental techniques, such LC-MS/MS, co-immunoprecipitation, DARTS analysis, LiP-MS, study the mechanistic actions taurine. showed taurocholic significantly upregulated aged islets. Pretreatment inhibited naturally chemically induced senescent inflammatory program, oxidative stress, defective insulin secretion β-cells. SLC6A6 required mediate exogenous uptake, inhibition abolished anti-senescent Taurine bound CKDN2AIP interaction p53, thereby promoting degradation suppressing p53-dependent program. Our findings suggest increasing uptake might be feasible approach preserve targeting response.

Язык: Английский

Процитировано

0