Nutrition & Diabetes最新文献

{"title":"Correction: Trends in Children's Dietary Inflammatory Index and association with prediabetes in U.S. adolescents.","authors":"Zisu Chen, Jing Wu, Kepeng Ai, Zhuying Bu, Wenquan Niu, Min Li","doi":"10.1038/s41387-025-00393-8","DOIUrl":"https://doi.org/10.1038/s41387-025-00393-8","url":null,"abstract":"","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"38"},"PeriodicalIF":5.2,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145252140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketogenic diet ameliorates MASLD via balancing mitochondrial dynamics and improving mitochondrial dysfunction.","authors":"Yuehua You, Hongbin Ni, Qin Ma, Lincheng Jiang, Jingshu Cai, Wenjun He, Xiaojing Lin, Kemeng Li, Zhuyun Wang, Weiyan Yan, Xiaoqiu Xiao, Li Ma","doi":"10.1038/s41387-025-00391-w","DOIUrl":"https://doi.org/10.1038/s41387-025-00391-w","url":null,"abstract":"<p><strong>Background & aims: </strong>Ketogenic diet (KD) is recognized as an effective lifestyle intervention for managing metabolic dysfunction-associated steatotic liver disease (MASLD). This research aimed to assess the impact of KD on metabolic parameters in MASLD mice and elucidate the underlying mechanism.</p><p><strong>Methods: </strong>High-fat diet (HFD)-induced MASLD mice were subjected to KD for 2 weeks. Researchers measured hepatic fat, plasma Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) levels to assess metabolic changes. Hepatic mitochondrial dynamics were examined using transmission electron microscopy and Western blot. Mitochondrial functions were evaluated through Quantitative Polymerase Chain Reaction (qPCR) and measurement of ATP content. In vitro, HepG2 cells were treated with palmitate (PA), β-hydroxybutyric acid (β-OHB), and/or the mitochondrial fusion inhibitor MFI8 to study mitochondrial morphology, function, and lipid deposition.</p><p><strong>Results: </strong>KD feeding partially improved the MASLD phenotype and reduced Fission 1 protein (Fis1) and Dynamin-related protein 1 (Drp1) levels in the livers of MASLD mice. Additionally, KD ameliorated HFD-stimulated mitochondrial dysfunctions, as evidenced by elevated ATP levels and upregulation of key genes responsible for fatty-acid-oxidation. β-OHB mitigated PA-stimulated mitochondrial dysfunction and fission in HepG2 cells. Furthermore, β-OHB attenuated PA-stimulated lipid deposition, with this effect being counteracted by MFI8.</p><p><strong>Conclusions: </strong>Our study suggests that a 2-week KD partially alleviates lipid deposition, restores mitochondrial dynamics balance, and improves mitochondrial dysfunctions in the livers of MASLD mice.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"37"},"PeriodicalIF":5.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary formaldehyde: a silent aggravator of diabetes and cognitive impairments.","authors":"Hanyuan Xu, Haishu Chen, Yihao Li, Tiancheng Luo, Danrui Zhao, Xiaoxiao Chen, Haozhan Zhang, Xinyun Hu, Hui Xu, Yiquan Wang, Yangping Shentu, Zhiqian Tong","doi":"10.1038/s41387-025-00390-x","DOIUrl":"10.1038/s41387-025-00390-x","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a chronic metabolic disorder associated with a range of serious complications, including insulin resistance (IR) and cognitive impairments. IR is recognized as a high-risk factor for the development of cognitive decline. However, it remains unclear which endogenous or exogenous factors induce these two pathological features. Recent studies indicate that certain diets, environmental pollutants, and genetic deficiencies or polymorphisms influence the metabolism of endogenous formaldehyde. Formaldehyde has been implicated in the onset of DM. Notably, elevated levels of formaldehyde have been detected in the blood, peripheral organs (such as the spleen and liver), and brains of both DM patients and animal models of diabetes. Formaldehyde-induced hyperglycemia and high glucose levels generate formaldehyde, creating a vicious cycle that speeds up diabetic complications. Further, excessive formaldehyde induces IR through three distinct mechanisms: alteration of the biologically active conformation of insulin, reduction in insulin receptor expression, and modification of insulin receptor structure. In addition, excessive formaldehyde can impair cognitive functions by inhibiting N-methyl-D-aspartate (NMDA) receptors and exacerbating brain IR. In this review, we discuss the pivotal role of diet-derived formaldehyde in diabetes and propose that reduction of formaldehyde by the formaldehyde scavengers may be a new strategy for treating DM patients.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"35"},"PeriodicalIF":5.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kefir-derived exopolysaccharide ameliorates hyperglycemic control and beta cell integrity in a rat model of type 2 diabetes mellitus.","authors":"Chih-Ching Yen, Chung-Liang Tsai, Gary Ro-Lin Chang, Chi-Hua Ko, Min-Yu Tu, Ying-Wei Lan, Hsiao-Ling Chen, Chuan-Mu Chen","doi":"10.1038/s41387-025-00388-5","DOIUrl":"10.1038/s41387-025-00388-5","url":null,"abstract":"<p><strong>Objective: </strong>Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated blood glucose levels due to insulin deficiency or resistance. While conventional treatments are effective, integrating nutraceuticals that aid in blood sugar control is crucial for patients with low compliance or prediabetes. This study aimed to assess the efficacy of kefir-derived exopolysaccharides (KEPS) in ameliorating type 2 DM in rats induced by streptozotocin (STZ) and a high-fat diet.</p><p><strong>Results: </strong>Eight-week-old male SD rats were fed a high-fat diet for 4 weeks and subsequently administered STZ (35 mg/kg body weight) via intraperitoneal injection to induce type 2 diabetes. Diabetic rats were randomly assigned to three groups: untreated diabetes (mock), diabetic rats + high-dose KEPS (STZ-KEPSH), and diabetic rats + low-dose KEPS (STZ-KEPSL), and treated for an additional 4 weeks. An age-matched SD rat group without STZ induction was used as a control. Our findings demonstrate that high-dose KEPS administration in diabetic rats enhances hepatic glucose uptake and stabilizes blood glucose levels by upregulating GLUT2 protein expression and PI3k phosphorylation in liver cells. KEPS mitigates lipid production, reduces β cell damage, and preserves islet cell integrity, thereby improving insulin sensitivity and alleviating diabetes symptoms. High-dose KEPS treatment also exhibits less renal enlargement and lower kidney-to-body weight ratio than the diabetic group.</p><p><strong>Conclusion: </strong>Exopolysaccharides derived from kefir show promising potential in managing type 2 diabetes mellitus in rats, suggesting a viable nutraceutical therapy. Further research is needed to validate these findings in human subjects.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"36"},"PeriodicalIF":5.2,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of turmeric/curcumin supplementation on anthropometric indices in subjects with prediabetes and type 2 diabetes mellitus: A GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials.","authors":"Mohammadreza Moradi Baniasadi, Pishva Arzhang, Azin Setayesh, Maedeh Moradi, Ensieh Nasli-Esfahani, Leila Azadbakht","doi":"10.1038/s41387-025-00386-7","DOIUrl":"10.1038/s41387-025-00386-7","url":null,"abstract":"<p><p>The effective management of diabetes, a prevalent metabolic condition globally, relies on paying close attention to anthropometric measurements, while recent years have seen a growing interest in researching the potential anti-obesity properties of turmeric/curcumin. In this systematic review and dose-response meta-analysis of randomized controlled trials, the impact of turmeric/curcumin supplementation on anthropometric indices in individuals with prediabetes and type 2 diabetes mellitus (T2DM) was assessed. PubMed, Cochrane Library, Web of Science, Scopus, and Google Scholar were searched to identify relevant records published from 1 January 1990 to 1 June 2024. Random-effects meta-analysis was performed to evaluate the weighted mean difference (WMD) and 95% confidence interval (CI), with a p-value ≤ 0.05 indicating statistical significance. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence. Twenty randomized controlled trials (RCTs) were included in the meta-analysis. Pooled analysis displayed that supplementation with turmeric/curcumin significantly decreased body weight (WMD: -1.9 kg; 95% CI: -2.9 to -0.9; P ≤ 0.001; GRADE = low), waist circumference (WMD: -1.9 cm; 95% CI: -3.5 to -0.2; P = 0.024; GRADE = low), fat mass% (WMD: -2.9%; 95% CI: -5.6 to -0.1, P = 0.041; GRADE = very low), and hip circumference (WMD: -1.0 cm; 95% CI: -1.2 to -0.8; P ≤ 0.001; GRADE = moderate) but no effects on body mass index and waist-to-hip ratio in people with T2DM. In individuals with prediabetes, body weight (WMD: -2.5 kg; 95% CI: -4.8 to -0.2; P = 0.037; GRADE = moderate) and waist circumference (WMD: -2.9 cm; 95% CI: -5.3 to -0.6; P = 0.015; GRADE = moderate) were significantly lower in the turmeric/curcumin supplement-treated group than their untreated counterparts. The study found that turmeric/curcumin has a beneficial effect on some obesity indicators, which could contribute to weight management in individuals with prediabetes and T2DM. Systematic Review Registration: This study was registered at PROSPERO as CRD42023440612.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"34"},"PeriodicalIF":5.2,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between maternal serum essential trace element concentration in early pregnancy and gestational diabetes mellitus.","authors":"Jinlang Lyu, Peng Tang, Yuanyuan Wang, Na Han, Rong Zhang, Xiangming Yang, Yuelong Ji, Jue Liu, Bin Wang, Lailai Yan, Qin Li, Xu Ma, Hai-Jun Wang","doi":"10.1038/s41387-025-00389-4","DOIUrl":"10.1038/s41387-025-00389-4","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) remains a major pregnancy metabolic issue. Although evidence suggested that essential trace elements (ETEs) may alter glycemic regulation during pregnancy, their associations with GDM remained uncertain.</p><p><strong>Methods: </strong>From the Peking University Birth Cohort in Tongzhou (PKUBC-T) with a total of 5426 participants, we randomly selected 200 cases with GDM and 200 matched controls without GDM to conduct a nested case-control study. The matching was on maternal age ( ± 2 years) and gestational week at which the oral glucose tolerance test was performed. We evaluated the levels of six ETEs (Cu, Zn, Se, Mo, Co, Cr) in serum samples collected at the first trimester (10.3 ± 1.6 gestational weeks). Associations were assessed with unconditional logistic regressions and Bayesian kernel machine regression.</p><p><strong>Results: </strong>Serum Co concentrations in pregnant women with GDM (Median: 0.920 ug/L) were observed to be lower than in controls (Median: 0.973 ug/L). Compared to those with the lowest tertile, the pregnant women with the highest tertile of Co concentrations had decreased risk of GDM (OR = 0.56, 95% CI: 0.34-0.93, P = 0.024) in the adjusted models. The association was further confirmed in the multiple-exposure analysis. The overall concentrations of six ETE mixtures showed an inverse association with GDM although not significant.</p><p><strong>Conclusion: </strong>Our study added new evidence that maternal serum Co level was inversely associated with the risk of GDM, indicating that maternal deficiency of Co may play a role in the development of GDM.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"33"},"PeriodicalIF":5.2,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omentin-1 protects against endothelial dysfunction through the AMPK/KLF2/eNOS pathway in adult rat offspring exposed to maternal diabetes.","authors":"ChunXiang Wang, QingHua Wang, HaoShan Mai","doi":"10.1038/s41387-025-00387-6","DOIUrl":"10.1038/s41387-025-00387-6","url":null,"abstract":"<p><strong>Objective: </strong>Exposure to gestational diabetes mellitus appears to produce several effects on offspring, including increased rates of early-onset cardiovascular disease from childhood to early adulthood. In this study, we investigated the protection of human omentin-1 against endothelial dysfunction resulting from exposure to maternal diabetes in adult rat offspring.</p><p><strong>Methods: </strong>Twelve adult control mother offspring (CMO) were injected with rh-omentin or saline, and 12 adult diabetic mother offspring (DMO) were injected with rh-omentin or saline. The mesenteric artery rings of rh-omentin-injected DMO were incubated with Compound C (an AMPK inhibitor). The vascular reactivity of rat mesenteric artery rings was evaluated by treating with PE (10^-9-10^-5M) and Ach (10^-9-10^-5M). The mesenteric arterial endothelial cells (AECs) isolated from different groups were incubated with A769662 (an AMPK agonist) and/or transfected with siRNA against KLF2 (si-KLF2) to confirm the AMPK/KLF2 pathway involved in the protection of omentin-1 against endothelial dysfunction.</p><p><strong>Results: </strong>Injection of rh-omentin alleviated PE-induced vasoconstriction and improved Ach-induced vasorelaxation in the mesenteric artery rings, inhibited phosphorylations of endoplasmic reticulum (ER) stress markers, prevented loss of phosphorylations of AMPK and endothelial nitric-oxide synthase (eNOS), increased nitric oxide production, reduced the level of reactive oxygen species, and promoted KLF2 expression in DMO. The AMPK inhibitor and KLF2 knockdown both eliminated these effects of omentin-1 on adult rat offspring exposed to maternal diabetes. KLF2 knockdown also weakened the effects of the AMPK agonist on adult rat offspring exposed to maternal diabetes.</p><p><strong>Conclusion: </strong>These findings point out that mentin-1 could protect adult rat offspring against endothelial dysfunction, including endothelium impairment, ER stress, and oxidative stress resulting from exposure to maternal diabetes through the AMPK/KLF2/eNOS pathway.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"32"},"PeriodicalIF":5.2,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute glycaemic response of orange juice consumption with breakfast in individuals with type 2 diabetes: a randomized cross-over trial.","authors":"Kenneth Verboven, Lisa Van Ryckeghem, Ralf Schweiggert, Christof B Steingass, Tin Gojevic, Carrie H S Ruxton, Dominique Hansen","doi":"10.1038/s41387-025-00385-8","DOIUrl":"10.1038/s41387-025-00385-8","url":null,"abstract":"<p><strong>Background/objectives: </strong>Sugar-sweetened beverages are associated with an increased risk of obesity and type 2 diabetes (T2DM) and show clear differential metabolic responses compared with 100% fruit juice, which is unsweetened by law. This study investigated whether the postprandial glycaemic response following a standardized breakfast differed when accompanied by 100% orange juice, equivalent whole orange, or a sugar-sweetened control beverage in individuals with well-controlled T2DM.</p><p><strong>Subjects/methods: </strong>Fifteen individuals with T2DM (60 ± 6 y; BMI 28.7 ± 5.0 kg/m², HbA1C 49 ± 3 mmol/mol (6.6 ± 0.3%)) participated in this randomized cross-over trial. They consumed a standardized breakfast served with either 250 mL of 100% orange juice, a sugar-sweetened orange-flavoured beverage or whole orange pieces with identical total sugar content. Postprandial glycaemic and insulinaemic responses were checked during 4 h.</p><p><strong>Results: </strong>Following a single intake, no significant differences were found in acute glucose or insulin responses (expressed as total or incremental area under the curve or peak values; p_treatment > 0.05, respectively) when either whole orange pieces, orange juice or a sugar-sweetened control beverage were consumed with a standard high carbohydrate meal. Capillary glucose responses did not differ between conditions (p_treatment > 0.05).</p><p><strong>Conclusion: </strong>Acute glycaemic control in individuals with well-controlled T2DM is not significantly influenced by serving orange juice, whole orange pieces or a sugar-sweetened beverage with a standard high-carbohydrate meal.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"31"},"PeriodicalIF":4.6,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food noise: definition, measurement, and future research directions.","authors":"Emily J Dhurandhar, Kevin C Maki, Nikhil V Dhurandhar, Theodore K Kyle, Sydney Yurkow, Misty A W Hawkins, Jon Agley, Emily H Ho, Lawrence J Cheskin, Thorkild I A Sørensen, Xi Rita Wang, David B Allison","doi":"10.1038/s41387-025-00382-x","DOIUrl":"10.1038/s41387-025-00382-x","url":null,"abstract":"<p><p>The term food noise has been recently popularized by individuals managing their weight or adhering to specific diets for health reasons. Anecdotal evidence from patients and clinical observations suggests that food noise involves constant preoccupation with food-related decisions-such as which foods to eat, caloric intake, macronutrient balance, and meal timing-which can become intrusive and unpleasant. Food noise also appears to affect cognitive burden and quality of life, and is being cited as one reason weight-loss attempts fail. The increase in public discourse about food noise has highlighted its potential significance, yet a formal clinical definition and method of measurement of food noise are lacking. Herein, we define food noise through clinical and patient anecdotes, describe initial research validating a food noise questionnaire, and outline future research directions. The formal definition of food noise is persistent thoughts about food that are perceived by the individual as being unwanted and/or dysphoric and may cause harm to the individual, including social, mental, or physical problems. Food noise is distinguished from routine food-related thoughts by its intensity and intrusiveness, resembling rumination. We describe our initial research developing the Ro Allison Indiana Dhurandhar- Food Noise Inventory (RAID-FN Inventory) to measure food noise. We also outline future areas of research, including exploring the prevalence and physiological underpinnings of food noise and the role of cultural and sociodemographic factors. The effects of glucagon-like peptide 1 (GLP-1) receptor agonists on food noise, the potential role of food noise in weight management and metabolic health, understanding food noise's impact on health outcomes and quality of life, the stigma associated with food noise, and the potential influence of food noise on public health policies are discussed. Future research should aim to refine definitions, improve measurement tools, and evaluate therapeutic strategies for managing food noise.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"30"},"PeriodicalIF":5.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the role of increased SK3 expression in sulfonylurea resistance triggered by prolonged exposure.","authors":"Jung Gyu Park, Minseok Kim, Sungje Yoo, Sun Wook Hwang, Jongsoo Mok, Joonghoon Park, Keon Wook Kang","doi":"10.1038/s41387-025-00384-9","DOIUrl":"10.1038/s41387-025-00384-9","url":null,"abstract":"<p><strong>Background: </strong>Sulfonylureas have long been utilized in the management of type-2 diabetes mellitus (T2DM) due to their insulin-secretagogue properties. However, their clinical efficacy is hindered by the risk of severe hypoglycemia and secondary sulfonylurea failure. While the mechanisms underlying sulfonylurea-induced hypoglycemia are well-documented, the precise factors contributing to sulfonylurea resistance (SR) remain poorly understood. This study aims to elucidate the molecular basis of SR in insulinoma cells and an animal model.</p><p><strong>Methods: </strong>INS-1E, rat insulinoma cells, were exposed to 10 μM glibenclamide for 7 days to induce sulfonylurea resistance (SR). Sprague-Dawley (SD) rats were fed a diet containing 0.01% glibenclamide for 3 weeks to induce sulfonylurea resistance.</p><p><strong>Results: </strong>Insulinoma cells resistant to sulfonylureas exhibited elevated resting membrane potentials compared to sensitive cells. Transcriptome analysis revealed differential expression of genes, notably highlighting the significance of kcnn3 (Potassium Calcium-Activated Channel Subfamily N Member 3) in SR insulinoma cells. Western blot analysis confirmed the upregulation of SK3 protein in correlation with the duration of sulfonylurea exposure. Long-term administration of sulfonylureas in SD rats led to a diminished anti-diabetic response and increased SK3 expression in islets.</p><p><strong>Conclusion: </strong>This study elucidates the molecular mechanisms underlying SR, with a specific focus on the overexpression of the SK3 channel in insulinoma cells. These findings enhance our understanding of the challenges associated with prolonged sulfonylurea therapy in the management of T2DM.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"29"},"PeriodicalIF":4.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}