Diabetes最新文献

{"title":"An Essential Role of IER3IP1 in β-Cell Development and Proinsulin Trafficking.","authors":"Wenli Feng, Peter Arvan, Ming Liu","doi":"10.2337/dbi24-0045","DOIUrl":"10.2337/dbi24-0045","url":null,"abstract":"","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":"74 4","pages":"455-457"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671957","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":"Strong Association of Autoantibodies Targeting Deamidated Extracellular Epitopes of Insulinoma Antigen-2 With Clinical Onset of Type 1 Diabetes.","authors":"Xiaofan Jia, Janet M Wenzlau, Caiguo Zhang, Fran Dong, Kathleen Waugh, R David Leslie, Marian J Rewers, Aaron W Michels, Liping Yu","doi":"10.2337/db24-0571","DOIUrl":"10.2337/db24-0571","url":null,"abstract":"<p><strong>Article highlights: </strong>CD4+ T cells from patients with type 1 diabetes (T1D) have a significant response to post-translationally modified (PTM) deamidated IA-2 peptides; autoantibodies to these PTM neoepitopes remain to be identified in T1D. We aimed to identify autoantibodies specifically targeting reported T-cell reactive, deamidated epitopes of IA-2 and explore their relationship with T1D development. Autoantibodies to deamidated IA-2 were specific to deamidated epitopes and were predominantly present during the late stages of T1D development, challenging the hypothesis that the loss of immune tolerance occurs via post-translational modification of islet antigens. Newly identified autoantibodies to deamidated IA-2 are new biomarkers of islet autoimmunity and have the potential to aid in T1D diagnosis.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"544-553"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018796","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":"Cisplatin Exposure Dysregulates Insulin Secretion in Male and Female Mice.","authors":"Lahari Basu, Lili Grieco-St-Pierre, Ma Enrica Angela Ching, John D H Stead, Antonio A Hanson, Jana Palaniyandi, Erin van Zyl, Myriam P Hoyeck, Kelsea S McKay, Kyle A van Allen, Hyojin Lee, Xiao-Qing Dai, Austin Bautista, Evgenia Fadzeyeva, Erin E Mulvihill, Carole L Yauk, Jan A Mennigen, Patrick E MacDonald, Jennifer E Bruin","doi":"10.2337/db24-0419","DOIUrl":"10.2337/db24-0419","url":null,"abstract":"<p><strong>Article highlights: </strong>Cancer survivors who receive cisplatin chemotherapy have an increased risk of type 2 diabetes, but the underlying mechanisms remain unclear. The aim of this study was to investigate whether cisplatin impacts β-cell health and function, thereby contributing to increased type 2 diabetes risk in cancer survivors. In vivo and in vitro cisplatin exposure dysregulated insulin secretion in male and female mice. In vitro cisplatin exposure reduced oxygen consumption, impaired β-cell exocytotic capacity, and altered expression of genes within the insulin secretion pathway in mouse islets. Understanding how chemotherapeutic drugs cause β-cell injury is critical for designing targeted interventions to reduce the risk of cancer survivors developing type 2 diabetes after treatment.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"528-543"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980958","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":"IP6K1 Rewires LKB1 Signaling to Mediate Hyperglycemic Endothelial Senescence.","authors":"Changchang Xing, Linhui Shi, Limei Zhu, Tim Aguirre, Ji Qi, Yuanyuan Chen, Yue Liu, Alfred C Chin, Hong Zhu, Dorothea Fiedler, Alex F Chen, Chenglai Fu","doi":"10.2337/db24-0706","DOIUrl":"10.2337/db24-0706","url":null,"abstract":"<p><strong>Article highlights: </strong>Diabetes is a major risk factor for cardiovascular diseases. The mechanisms of hyperglycemia-induced endothelial dysfunction have been elusive. We found that inositol hexakisphosphate kinase 1 (IP6K1) mediates hyperglycemia-induced endothelial senescence by switching liver kinase B1 (LKB1) activation of the AMPK pathway to activation of the p53 pathway. Hyperglycemia upregulates IP6K1, which stabilizes LKB1 by disrupting Hsp/Hsc70 and carboxyl terminus of Hsc70-interacting protein-mediated LKB1 degradation but suppresses LKB1-dependent AMPK activation. Elevated LKB1 binds more to p53, resulting in p53-dependent endothelial senescence. Endothelial cell-specific deletion of IP6K1 attenuates, whereas endothelial cell-specific overexpression of IP6K1 exaggerates, hyperglycemia-induced endothelial senescence.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"486-501"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960459","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":"Identification of CD209 as an Intervention Target for Type 2 Diabetes After COVID-19 Infection: Insights From Proteome-Wide Mendelian Randomization.","authors":"Jiaying Zhang, Feng Jiao, Zhenqian Wang, Chenfeng Zou, Xiangjun Du, Dewei Ye, Guozhi Jiang","doi":"10.2337/db24-0677","DOIUrl":"10.2337/db24-0677","url":null,"abstract":"<p><strong>Article highlights: </strong>Increasing evidence links coronavirus disease 2019 (COVID-19) infection with heightened type 2 diabetes (T2D) risk; however, the mechanisms underlying this relationship remain poorly understood. We aimed to identify mediating proteins linking COVID-19 infection with T2D, elucidating how COVID-19 might heighten T2D risk. Protein CD209 and central obesity potentially play a crucial role between COVID-19 susceptibility and T2D. Our results highlight CD209 as a potential intervention target for T2D prevention following COVID-19 infection.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"619-629"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054571","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":"Rnd3 Ameliorates Diabetic Cardiac Microvascular Injury via Facilitating Trim40-Mediated Rock1 Ubiquitination.","authors":"Jie Lin, Xuebin Zhang, Wen Ge, Yu Duan, Xiao Zhang, Yan Zhang, Xinchun Dai, Mengyuan Jiang, Xiaohua Zhang, Jiye Zhang, Huanhuan Qiang, Dongdong Sun","doi":"10.2337/db24-0543","DOIUrl":"10.2337/db24-0543","url":null,"abstract":"<p><strong>Article highlights: </strong>Impaired cardiac microvascular function is a significant contributor to diabetic cardiomyopathy. Rnd3 expression is notably downregulated in cardiac microvascular endothelial cells under diabetic conditions. Rnd3 overexpression mitigates diabetic myocardial microvascular injury and improves cardiac function through the Rock1/myosin light chain signaling pathway. Rnd3 facilitates the recruitment and interaction with Trim40 to promote Rock1 ubiquitination, thereby preserving endothelial barrier integrity in the diabetic heart.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"569-584"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960460","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":"Ablation of FAM210A in Brown Adipocytes of Mice Exacerbates High-Fat Diet-Induced Metabolic Dysfunction.","authors":"Jiamin Qiu, Mennatallah A Khedr, Meijin Pan, Christina R Ferreira, Jingjuan Chen, Madigan M Snyder, Kolapo M Ajuwon, Feng Yue, Shihuan Kuang","doi":"10.2337/db24-0294","DOIUrl":"10.2337/db24-0294","url":null,"abstract":"<p><p>Thermogenesis of brown adipose tissue (BAT) provides metabolic benefits against pathologic conditions, such as type 2 diabetes, obesity, cardiovascular disease, and cancer. The thermogenic function of BAT relies on mitochondria, but whether mitochondrial remodeling is required for the beneficial effects of BAT remains unclear. We recently identified FAM210A as a BAT-enriched mitochondrial protein essential for cold-induced thermogenesis through the modulation of OPA1-dependent cristae remodeling. Here, we report a key role of FAM210A in the systemic response to a high-fat diet (HFD). We discovered that an HFD suppressed FAM210A expression, associated with excessive OPA1 cleavage in BAT. Ucp1-Cre-driven BAT-specific Fam210a knockout (Fam210aUKO) similarly elevated OPA1 cleavage, accompanied by whitening of BAT. When subjected to an HFD, Fam210aUKO mice gained similar fat mass as sibling control mice but developed glucose intolerance, insulin resistance, and liver steatosis. The metabolic dysfunction was associated with overall increased lipid content in both the liver and BAT. Additionally, Fam210aUKO leads to inflammation in white adipose tissue. These data demonstrate that FAM210A in BAT is necessary for counteracting HFD-induced metabolic dysfunction but not obesity.</p><p><strong>Article highlights: </strong>FAM210A regulates cold-induced mitochondrial remodeling through control of OPA1 cleavage, but whether it also plays a role in high-fat diet (HFD)-induced cristae remodeling is unknown. We asked if an HFD would alter the FAM210A level and OPA1 cleavage in brown adipose tissue (BAT) and how FAM210A loss of function would affect diet-induced obesity in mice. We found that an HFD diminished FAM210A expression and accelerated OPA1 cleavage in BAT, and Fam210a knockout exacerbated HFD-induced whitening of BAT, cold intolerance, liver steatosis, white adipose tissue inflammation, and metabolic dysfunction. Our work reveals a physiologic role of FAM210A-mediated BAT mitochondrial remodeling in systemic adaptation to an HFD and suggests that BAT mitochondria may be targeted to treat diet-induced metabolic dysfunction.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"282-294"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741704","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":"Comment on Chanoine et al. Is Hyperactive mTORC1 Signaling Responsible for the Phenotypic Expression (Diabetes, Hypoacusis) of the m.3243A>G Variant?","authors":"Josef Finsterer","doi":"10.2337/db24-1061","DOIUrl":"10.2337/db24-1061","url":null,"abstract":"","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":"74 3","pages":"e6-e7"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470371","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":"Phenotypic Versus Genetic Mismatch of BMI and Type 2 Diabetes: Evidence From Two Prospective Cohort Studies.","authors":"Aolin Li, Shuo Gong, Canqing Yu, Pei Pei, Ling Yang, Iona Y Millwood, Robin G Walters, Yiping Chen, Huaidong Du, Xiaoming Yang, Wei Hou, Junshi Chen, Zhengming Chen, Jun Lv, Liming Li, Dianjianyi Sun","doi":"10.2337/db24-0736","DOIUrl":"10.2337/db24-0736","url":null,"abstract":"<p><p>Little is known about the population-based mismatch between phenotypic and genetic BMI (BMI-PGM) and its association with type 2 diabetes. We therefore used data from the China Kadoorie Biobank and UK Biobank and calculated BMI-PGM for each participant as the difference between the percentile for adjusted BMI at baseline and the percentile for adjusted polygenic risk score for BMI. Participants were categorized into discordantly low (BMI-PGM < the first quartile), concordant (the first quartile ≤ BMI-PGM < the third quartile), and discordantly high (BMI-PGM ≥ the third quartile) groups. We calculated adjusted hazard ratios (HRs) for the association of BMI-PGM and type 2 diabetes using Cox proportional hazard models in each cohort, and combined HRs using random-effects meta-analyses. During a median follow-up of 12 years for both cohorts, BMI-PGM was associated with the risk of type 2 diabetes, with the discordantly low group showing reduced risk and the discordantly high group showing elevated risk compared with the concordant group, independent of BMI and other conventional risk factors. In addition, normal-weight individuals with discordantly high BMI-PGM faced a higher risk of type 2 diabetes than overweight individuals. These findings suggest that BMI-PGM may play a potential role in reassessing the risk of type 2 diabetes, particularly among normal-weight populations.</p><p><strong>Article highlights: </strong>Social developments have fostered an \"obesogenic environment\" that exacerbated phenotypic versus genetic mismatch of BMI (BMI-PGM) and the risk of type 2 diabetes. The study quantified BMI-PGM and examined its association with type 2 diabetes independent of BMI and other conventional factors. The risk of type 2 diabetes was lower in the discordantly low BMI-PGM group and higher in the discordantly high BMI-PGM group, with concordant BMI-PGM group as reference. These findings indicate the potential to reassess type 2 diabetes risk by quantifying BMI-PGM on individual levels.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"320-331"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831440","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":"Improved Afternoon Hepatic Glucose Disposal and Storage Requires Morning Engagement of Hepatic Insulin Receptors.","authors":"Hannah L Waterman, Mary Courtney Moore, Marta S Smith, Ben Farmer, Kalisha Yankey, Melanie Scott, Dale S Edgerton, Alan D Cherrington","doi":"10.2337/db24-0786","DOIUrl":"10.2337/db24-0786","url":null,"abstract":"<p><p>Glucose tolerance improves significantly upon consuming a second, identical meal later in the day (second-meal phenomenon). We previously established that morning hyperinsulinemia primes the liver for increased afternoon hepatic glucose uptake (HGU). Although the route of insulin delivery is an important determinant of the mechanisms by which insulin regulates liver glucose metabolism (direct hepatic vs. indirect insulin action), it is not known whether insulin's delivery route affects the second-meal response. To determine whether morning peripheral insulin delivery (as occurs clinically, i.e., subcutaneously) can enhance afternoon HGU, conscious dogs were treated in the morning with insulin delivered either via the portal vein or peripherally (leg vein), while glucose was infused to maintain euglycemia. Consequently, arterial insulin levels increased similarly in both groups, but relative hepatic insulin deficiency occurred with peripheral insulin delivery. In the afternoon, all animals were challenged with the same hyperinsulinemic-hyperglycemic clamp to simulate identical postprandial-like conditions. The substantial enhancement of HGU in the afternoon caused by morning portal vein insulin delivery was lost when insulin was delivered peripherally. This indicates that morning insulin does not cause the second-meal phenomenon via its indirect actions on the liver but, rather, through direct activation of hepatic insulin signaling.</p><p><strong>Article highlights: </strong>Morning insulin delivery primes the liver for increased hepatic glucose uptake (HGU) later in the day, but until now, the mechanism (direct hepatic and/or indirect insulin action) remained unclear. This study compared insulin infusion via endogenous (hepatic portal vein) and clinical (peripheral) routes to assess their impact on afternoon hepatic glucose disposal. Arterial hyperinsulinemia in the morning, without a concomitant increase in insulin at the liver, failed to induce a significant enhancing effect on afternoon HGU and glycogen storage, unlike morning hepatic portal vein insulin delivery, which did. These findings highlight the importance of achieving appropriate hepatic insulin exposure in the morning to effectively prime the liver for enhanced glucose disposal later in the day.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"270-281"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741707","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}