Diabetes最新文献

{"title":"Novel Function of Osteoprotegerin in the Modulation of Glucose Metabolism in the Liver via mTORC1.","authors":"Sheng Qiu, Xia Wang, Ke Li, Siliang Zhang, Yerui Lai, Qiao Mi, Min Yang, Dongfang Liu, Ling Li, Qinan Wu, Mengliu Yang","doi":"10.2337/db25-0207","DOIUrl":"https://doi.org/10.2337/db25-0207","url":null,"abstract":"<p><strong>Article highlights: </strong>Methylation of the Opg promoter inhibits hepatic OPG expression in obese mice. Hepatic OPG regulates glucose metabolism and insulin sensitivity in obese mice. OPG regulates glucose metabolism through interaction with mammalian target of rapamycin complex 1 (Raptor). Opg deficiency in mice reduces age-related metabolic dysfunction.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Association Study of Hypoglycemia in Adults With Diabetes in the Million Veteran Program.","authors":"Sridharan Raghavan, Elizabeth Litkowski, Aubrey Jensen, Brian Charest, Zeyuan Wang, Qin Hui, Hua-Chang Chen, Mary K Rhee, Aaron Leong, James B Meigs, Leslie Lange, Ethan Lange, Peter Reaven, Adriana Hung, Jin Zhou, Yan V Sun, Lawrence S Phillips","doi":"10.2337/db25-0304","DOIUrl":"https://doi.org/10.2337/db25-0304","url":null,"abstract":"<p><strong>Article highlights: </strong>Genetic variants associated with hypoglycemia risk in individuals with medication-treated diabetes have not been evaluated genome-wide. The specific question we asked was whether common genetic variants are associated with hypoglycemia among individuals with diabetes treated with glucose-lowering medications. We found four genomic loci were associated with hypoglycemia in a genome-wide association study. One locus-on chromosome 6-was associated with hypoglycemia only in individuals with likely type 1 diabetes, and two loci-on chromosome 2 and chromosome 6-were associated with hypoglycemia only in the context of treatment with sulfonylureas (chromosome 2) or with insulin (chromosome 6). Genetic variants may help identify individuals with diabetes at increased hypoglycemia risk, but additional study is needed to address the clinical utility of genetic data to inform hypoglycemia risk.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics Integration of Epigenetics, Proteomics, and Metabolomics Identifies Putative Drug Targets and Improves Early Prediction for Diabetes.","authors":"Wenran Li, Yingyu Cheng, Aoyuan Cui, Mengyao Huang, Qingxia Huang, Qi Wang, Mingfeng Xia, Jiange Qiu, Qianqian Peng, Jiarui Li, Huating Li, Yong Wang, Geng Zong, Yan Zheng, Jiucun Wang, Xin Gao, Chen Ding, Huiru Tang, Bing-Hua Jiang, Li Jin, Yu Li, Sijia Wang","doi":"10.2337/db25-0354","DOIUrl":"https://doi.org/10.2337/db25-0354","url":null,"abstract":"<p><strong>Article highlights: </strong>A total of 175 CpGs, 29 proteins, and 93 metabolites were identified as associated with diabetes, among which 43 CpGs and 25 metabolites were validated in an independent cohort. Causal and mediation analyses revealed 20 biomarkers and 190 signaling pathways involved in diabetes development. The integrative multiomics prioritization provides the community with an ordered list of diabetes biomarkers. We experimentally validated one of the prioritized proteins, COLEC11, and demonstrated its involvement in lipid metabolism. Our findings prioritize potential therapeutic targets and demonstrate that integrating multiomics biomarkers improves diabetes risk prediction beyond traditional clinical models.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Cell Neogenesis From the Pancreatic Ductal Epithelium Revealed Dynamically by Long-term Intravital Imaging.","authors":"Brandon Watts, Isabella Altilio, Óscar Alcázar, Silvia Álvarez-Cubela, Per-Olof Berggren, Midhat H Abdulreda, Ricardo L Pastori, Juan Domínguez-Bendala","doi":"10.2337/db25-0457","DOIUrl":"https://doi.org/10.2337/db25-0457","url":null,"abstract":"<p><strong>Article highlights: </strong>The adult pancreas' capacity to regenerate endocrine cells through ductal neogenesis has been disputed based on some pulse-chase lineage-tracing designs; however, no model described thus far has enabled the real-time study of regeneration in vivo. To facilitate long-term intravital imaging of pancreatic remodeling, we designed a novel system where pancreatic slices are transplanted into the anterior chamber of the eye of recipient mice. Using a transgenic mouse strain that enables the tracing of insulin-producing cells, we demonstrate that they arise dynamically from the ductal epithelium. Complementary work with human pancreatic slices suggests conservation of these mechanisms across species.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Metabolomics Reveals Potential Differences in Gut Microbiota-Associated Metabolites in Twins Discordant for Type 1 Diabetes.","authors":"Elizabeth R Flammer, Michael W Christopher, Esabella R Powers, Hali Broncucia, Andrea K Steck, Stephen E Gitelman, Timothy J Garrett, Heba M Ismail","doi":"10.2337/db25-0156","DOIUrl":"10.2337/db25-0156","url":null,"abstract":"<p><strong>Article highlights: </strong>We believed this cohort of twins discordant for type 1 diabetes (T1D) would allow for control over genetic variability to examine environmental factors. We aimed to identify differences in microbial and microbiota-associated metabolites in twins discordant for T1D to examine the effect of the gut microbiome on T1D. Thirteen metabolites were identified as significantly different. Our results show dysregulation of several microbial metabolites in twin pairs, suggesting the role of the gut microbiome in T1D pathogenesis.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights Into Postprandial Insulin-Glucagon Interactions and Their Impact on Glucose Flux After Protein-Glucose Coingestion in Humans.","authors":"Giang M Dao, Chistopher S Shaw, Andrew C Betik, Vicky Kuriel, Clinton R Bruce, Greg M Kowalski","doi":"10.2337/db25-0395","DOIUrl":"https://doi.org/10.2337/db25-0395","url":null,"abstract":"<p><p>Despite stimulating glucagon secretion, the mechanisms by which protein ingestion lowers glucose excursions remain unclear. We investigated this using the triple stable isotope glucose tracer technique to measure postprandial glucose fluxes. Eleven healthy adults completed three trials, ingesting 25 g glucose (25G; 100 kcal), 50 g glucose (50G; 200 kcal), or 25 g glucose plus 25 g whey protein (25WG; 200 kcal). Glucose excursions were lowest for 25WG. Glucagon increased approximately threefold with 25WG but was suppressed with 25G and 50G. Insulin and glucose-dependent insulinotropic polypeptide (GIP) were higher for 25WG versus 25G, whereas glucagon-like peptide 1 (GLP-1) was similar. Compared with 50G, 25WG produced a greater GIP but similar GLP-1 response, with a trend toward higher early-phase insulin. Endogenous glucose production (EGP) was less suppressed with 25WG (∼50%) versus 25G (∼70%) or 50G (∼80%). Compared with 25G, 25WG did not enhance glucose disposal (Rd) but reduced early-phase (30-60 min) glucose absorption. These findings confirm that protein-glucose coingestion robustly stimulates glucagon while enhancing GIP and insulin, leading to lower postprandial glucose excursions. Despite greater insulin secretion, the net glycemic benefit seems to stem from reduced early glucose absorption rather than increased Rd. This provides novel insights into the mechanisms by which protein improves postprandial glucose handling despite interfering with EGP suppression.</p><p><strong>Article highlights: </strong>Despite stimulating glucagon secretion, the addition of protein to carbohydrate typically lowers postprandial glucose excursions. The mechanisms underlying this phenomenon are incompletely understood. In healthy young adults, using the triple stable isotope glucose tracer technique, we investigated how whey protein and glucose coingestion modulates postprandial glucose fluxes. Despite stimulating glucagon secretion and impairing suppression of endogenous glucose production, whey protein-glucose coingestion significantly reduced glycemic excursions. Although whey protein-glucose coingestion strongly enhanced the insulin and glucose-dependent insulinotropic polypeptide (but not glucagon-like peptide 1) responses, whole-body glucose uptake was not enhanced; rather, the net glycemic benefit seemed to stem from reduced early-phase glucose absorption.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Dorzagliatin, a Glucokinase Activator, on α- and β-Cell Function in Individuals With Impaired and Normal Glucose Tolerance.","authors":"Zhengli Bai, Ke Wang, Tiffany Yau, Cadmon K P Lim, Sandra T F Tsoi, Baoqi Fan, Claudia H T Tam, Emily W M Poon, Andrea O Y Luk, Alice P S Kong, Ronald C W Ma, Ele Ferrannini, Andrea Mari, Li Chen, Juliana C N Chan, Elaine Chow","doi":"10.2337/db24-1130","DOIUrl":"https://doi.org/10.2337/db24-1130","url":null,"abstract":"<p><strong>Article highlights: </strong>Dorzagliatin is a dual-acting allosteric glucokinase (GCK) activator that increases β-cell glucose sensitivity and second-phase insulin in GCK monogenic diabetes of the young. Actions of dorzagliatin on α- and β-cell function in normal and impaired glucose tolerance are unknown. In this study, dorzagliatin increased second-phase insulin in individuals with impaired glucose tolerance while suppressing glucagon in participants with normal glucose tolerance during a hyperglycemic clamp. With increasing glucose, plasma glucagon and total GLP-1 levels declined progressively. A modest to moderate positive correlation between glucagon and total GLP-1 was observed under both dorzagliatin and placebo treatments.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipidomic Signatures of Insulin Resistance Identified From Hyperinsulinemic-Euglycemic Clamp Studies in Asian Men.","authors":"Sartaj Ahmad Mir, Kothandaraman Narasimhan, Jayagowtham K Annadurai, Vaitheeswari, Shanshan Ji, David Cameron-Smith, Johan G Eriksson, Melvin Khee-Shing Leow, Markus R Wenk, Federico Torta, Chin Meng Khoo","doi":"10.2337/db25-0010","DOIUrl":"10.2337/db25-0010","url":null,"abstract":"<p><strong>Article highlights: </strong>The underlying molecular pathogenesis of the Asian phenotype of insulin resistance remains to be understood. We carried out metabolic phenotyping of study participants without diabetes according to insulin sensitivity indices derived from hyperinsulinemic-euglycemic clamp procedures. We identified lipidomic signatures of insulin resistance and metabolic plasticity. These lipidomic signatures have the potential to help in risk stratification of insulin resistance and metabolic dysfunction for early intervention.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1489-1498"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes Spotlight: David J. Hodson, BVSc, PhD, FRCVS-Regulation of Insulin and Glucagon in Pancreatic Islet Biology.","authors":"Benjamin Page","doi":"10.2337/dbi25-0034","DOIUrl":"https://doi.org/10.2337/dbi25-0034","url":null,"abstract":"","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":"74 9","pages":"1443-1444"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144983750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Cell Function and Sensitivity to Incretins Before and After Roux-en-Y Gastric Bypass in Individuals With Type 2 Diabetes.","authors":"Maria S Svane, Morten Hindsø, Christoffer Martinussen, Carsten Dirksen, Nils B Jørgensen, Nora Hedbäck, Bolette Hartmann, Viggo B Kristiansen, Jens J Holst, Kirstine N Bojsen-Møller, Sten Madsbad","doi":"10.2337/db24-1054","DOIUrl":"10.2337/db24-1054","url":null,"abstract":"<p><strong>Article highlights: </strong>Roux-en-Y gastric bypass improves glycemic control in patients with type 2 diabetes, but the impact of the improved glycemic control on β-cell sensitivity to glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is sparsely described. GLP-1 and GIP potentiated insulin secretion during clamped hyperglycemia before and after surgery, but, when related to the response to glucose alone, the relative potentiating effects of GIP (on first-phase insulin secretion) and GLP-1 (on first- and second-phase insulin secretion) were reduced postoperatively. The improvement in β-cell function after Roux-en-Y gastric bypass in patients with type 2 diabetes is not driven by improved β-cell sensitivity to incretins but rather other factors, including improved β-cell sensitivity to the changed glucose response and exaggerated postprandial GLP-1.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"1652-1663"},"PeriodicalIF":0.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}