Diabetes最新文献_第2页

Activation of the HPA axis does not explain non-responsiveness to GLP-1R agonist treatment in individuals with type 2 diabetes 激活 HPA 轴不能解释 2 型糖尿病患者对 GLP-1R 激动剂治疗无反应的原因

IF 7.7 1区医学

Diabetes Pub Date : 2024-11-19 DOI: 10.2337/db24-0463

Sevilay Tokgöz, Marti Boss, Theodorus JP Jansen, Rick Meijer, Cathelijne Frielink, Arianne C van Bon, Cees J Tack, Bastiaan E de Galan, Martin Gotthardt

{"title":"Activation of the HPA axis does not explain non-responsiveness to GLP-1R agonist treatment in individuals with type 2 diabetes","authors":"Sevilay Tokgöz, Marti Boss, Theodorus JP Jansen, Rick Meijer, Cathelijne Frielink, Arianne C van Bon, Cees J Tack, Bastiaan E de Galan, Martin Gotthardt","doi":"10.2337/db24-0463","DOIUrl":"https://doi.org/10.2337/db24-0463","url":null,"abstract":"Glucagon-like peptide 1 receptor (GLP-1R) agonists fail to reduce weight and improve glucose control in a sizable minority of people with type 2 diabetes. We hypothesized that stimulation of the hypothalamic-pituitary-adrenal (HPA) axis by GLP-1R agonists, thus inducing cortisol secretion, could explain this unresponsiveness to GLP-1R agonists. To assess the effects of GLP-1R agonist treatment on the HPA axis, we selected ten individuals with type 2 diabetes with (5 women/5 men) and nine without (4 women/5 men) an adequate response to GLP-1R agonists and used [68Ga]Ga-NODAGA-exendin-4 positron emission tomography (PET)/computed tomography (CT) to quantify GLP-1R expression in the pituitary. Oral glucose tolerance and 24 h urinary cortisol excretion was measured in all participants. Pituitary tracer uptake was observed in all participants with no significant difference between responders and non-responders. Pituitary tracer uptake correlated with the area under the curve for ACTH, urinary cortisol to creatinine ratio and age. Interestingly, men had higher pituitary tracer uptake than women. In conclusion, this study does not indicate a role for pituitary GLP-1R expression and HPA axis stimulation to explain the difference in treatment response to GLP-1R agonists among individuals with type 2 diabetes. The findings of substantial pituitary GLP-1R expression and the significant sex differences require further research.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"8 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Proteomic Signature of Body Mass Index and Risk of Type 2 Diabetes 体重指数与 2 型糖尿病风险的蛋白质组特征

IF 7.7 1区医学

Diabetes Pub Date : 2024-11-19 DOI: 10.2337/db24-0329

Xuan Wang, Hao Ma, Minghao Kou, Yoriko Heianza, Vivian Fonseca, Lu Qi

{"title":"Proteomic Signature of Body Mass Index and Risk of Type 2 Diabetes","authors":"Xuan Wang, Hao Ma, Minghao Kou, Yoriko Heianza, Vivian Fonseca, Lu Qi","doi":"10.2337/db24-0329","DOIUrl":"https://doi.org/10.2337/db24-0329","url":null,"abstract":"The obesity diagnosis by body mass index (BMI) exhibits considerable interindividual heterogeneity in metabolic phenotypes and risk of developing type 2 diabetes (T2D). We investigated the association of proteomic signature of BMI and T2D and examined whether the proteomic signature of BMI improves prediction of T2D risk. This study included 41,427 adults in the UK Biobank who were free of T2D at baseline and had complete data on proteomics metrics assessed by antibody based Olink assay. The main exposure was a proteomic BMI score (pro-BMI score) calculated from 67 pre-identified plasma proteins associated with BMI. During a median follow-up of 13.7 years, 2,030 incident events of T2D were documented. We observed that a higher proteomic BMI (pro-BMI) score was significantly associated with a higher risk of T2D independent of actual BMI, waist-to-hip ratio, and polygenic risk score for BMI (hazard ratio (HR) comparing the highest with the lowest quartiles was 3.81, 95% CI, 3.08 – 4.71). Pro- BMI score significantly increased the C index when added to a reference model with age, sex, and BMI (C index change, 0.023 [95%CI, 0.018 to 0.027]). Proteomic signature of BMI is significantly associated with the risk of T2D independent of BMI, WHR and genetic susceptibility to obesity. When added to actual BMI, the proteomic signature of BMI provides significant but modest improvement in discrimination.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"46 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Friend or foe: the paradoxical roles of MG53 in diabetes mellitus 朋友还是敌人：MG53 在糖尿病中的矛盾作用

IF 7.7 1区医学

Diabetes Pub Date : 2024-11-13 DOI: 10.2337/db24-0556

Shuangshuang Yuan, Qin Yu, Mao Luo, Jianbo Wu, Liqun Wang

{"title":"Friend or foe: the paradoxical roles of MG53 in diabetes mellitus","authors":"Shuangshuang Yuan, Qin Yu, Mao Luo, Jianbo Wu, Liqun Wang","doi":"10.2337/db24-0556","DOIUrl":"https://doi.org/10.2337/db24-0556","url":null,"abstract":"MG53 is predominantly expressed in striated muscles. The role of MG53 in diabetes mellitus has been gradually elucidated but is still full of controversy. Some reports have indicated that MG53 is upregulated in animal models with metabolic disorders, and that muscle-specific MG53 upregulation is sufficient to induce whole-body insulin resistance and metabolic syndrome through targeting both the insulin receptor (IR) and IR substrate-1 (IRS-1) for ubiquitin-dependent degradation. Additionally, MG53 has been identified as a myokine/cardiokine that is secreted from striated muscles into the bloodstream and circulating MG53 has further been shown to trigger insulin resistance by binding to the extracellular domain of the IR, thereby allosterically inhibiting insulin signaling. Conversely, other studies have reported findings that contradict these results. Specifically, no significant change in MG53 expression in striated muscles or serum has been observed in diabetic models, and the MG53-mediated degradation of IRS-1 may be insufficient to induce insulin resistance due to the compensatory roles of other IRS subtypes. Furthermore, sustained elevation of MG53 levels in serum or systemic administration of recombinant human MG53 (rhMG53) has shown no impact on metabolic function. In this review, we will fully characterize these two disparate views, strive to provide critical insights into their contrasts and propose several specific experimental approaches that may yield additional evidence. Our goal is to encourage the scientific community to elucidate the effects of MG53 on metabolic diseases and the molecular mechanisms involved, thereby providing the theoretical basis for the treatment of metabolic diseases and the applications of rhMG53.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"98 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovating Diabetes Care in Pregnancy: Do group care models improve outcomes and equity? 创新孕期糖尿病护理：集体护理模式能否改善疗效和公平性？

IF 7.7 1区医学

Diabetes Pub Date : 2024-11-12 DOI: 10.2337/dbi24-0006

Ebony B. Carter

引用次数: 0

The effect of small increases in blood glucose on insulin secretion and endogenous glucose production in humans 血糖小幅升高对人体胰岛素分泌和内源性葡萄糖生成的影响

IF 7.7 1区医学

Diabetes Pub Date : 2024-11-07 DOI: 10.2337/db24-0388

Clinton R. Bruce, Teddy Ang, Jason D. Toms, Giang M. Dao, Jean Liu, Glenn M. Ward, David N. O’Neal, Dale J. Morrison, Greg M. Kowalski

{"title":"The effect of small increases in blood glucose on insulin secretion and endogenous glucose production in humans","authors":"Clinton R. Bruce, Teddy Ang, Jason D. Toms, Giang M. Dao, Jean Liu, Glenn M. Ward, David N. O’Neal, Dale J. Morrison, Greg M. Kowalski","doi":"10.2337/db24-0388","DOIUrl":"https://doi.org/10.2337/db24-0388","url":null,"abstract":"Small glycemic increments (≤0.5 mmol/L) can exert suppressive actions on endogenous glucose production (EGP) however it is unclear if this is an insulin dependent or independent process. Here, we performed a low-rate glucose infusion in control participants without diabetes and in people with type 1 diabetes (T1D) to better understand this phenomenon. Glucose kinetics, hormones and metabolites were measured during a 1 mg/kg/min glucose infusion (90 min) which rapidly increased glucose by ∼0.3 mmol/L in control participants. Insulin concentrations and secretion quickly increased by ∼20%, resulting in a ∼40% suppression of EGP, while glucose disposal remained unchanged. Free fatty acids (FFA) and glucagon were gradually suppressed to ∼30% below baseline at 60 min. When repeated under constant basal insulin concentrations in participants with T1D, glucose infusion caused only partial and transient EGP suppression, hence glucose increased in a near-linear manner, reaching levels ∼2 mmol/L above baseline at 90 min. FFAs and glucagon remained unchanged, while glucose disposal modestly increased. This demonstrates that small glycemic increments exert subtle stimulatory effects on insulin secretion that have potent metabolic actions on the liver and adipose tissue. It is conceivable that subtle increases in glucose could potentially serve as a signal for β-cell adaptation.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"35 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging concepts and success stories in type 1 diabetes research: a roadmap for a bright future 1 型糖尿病研究的新概念和成功案例：光明未来的路线图

IF 7.7 1区医学

Diabetes Pub Date : 2024-10-24 DOI: 10.2337/db24-0439

Roberto Mallone, Emily Sims, Peter Achenbach, Chantal Mathieu, Alberto Pugliese, Mark Atkinson, Sanjoy Dutta, Carmella Evans-Molina, David Klatzmann, Anne Koralova, S. Alice Long, Lut Overbergh, Teresa Rodriguez-Calvo, Anette-Gabriele Ziegler, Sylvaine You

{"title":"Emerging concepts and success stories in type 1 diabetes research: a roadmap for a bright future","authors":"Roberto Mallone, Emily Sims, Peter Achenbach, Chantal Mathieu, Alberto Pugliese, Mark Atkinson, Sanjoy Dutta, Carmella Evans-Molina, David Klatzmann, Anne Koralova, S. Alice Long, Lut Overbergh, Teresa Rodriguez-Calvo, Anette-Gabriele Ziegler, Sylvaine You","doi":"10.2337/db24-0439","DOIUrl":"https://doi.org/10.2337/db24-0439","url":null,"abstract":"Type 1 diabetes treatment stands at a crucial and exciting crossroad since the 2022 U.S. Food and Drug Administration (FDA) approval of teplizumab to delay disease development. In this Perspective article, we discuss four major conceptual and practical issues that emerged as key to further advance type 1 diabetes research and therapies. First, collaborative networks leveraging the synergy between the type 1 diabetes research and care community members are key to fostering innovation, know-how and translation into the clinical arena worldwide. Second, recent clinical trials in presymptomatic stage 2 and recent-onset stage 3 disease have shown the promise, and potential pitfalls, of using immunomodulatory and/or beta-cell protective agents to achieve sustained remission or prevention. Third, the increasingly appreciated heterogeneity of clinical, immunological, and metabolic phenotypes and disease trajectories is of critical importance to advance the decision-making process for tailored type 1 diabetes care and therapy. Fourth, the clinical benefits of early diagnosis of beta-cell autoimmunity warrant consideration of general population screening for islet autoantibodies, which requires further efforts to address the technical, organizational and ethical challenges inherent to a sustainable program. Efforts are underway to integrate these four concepts into the future directions of type 1 diabetes research and therapy.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"194 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N 6-Methyladenosine demethylase FTO controls macrophage homeostasis in diabetic vasculopathy N 6-甲基腺苷去甲基化酶 FTO 控制糖尿病血管病变中巨噬细胞的稳态

IF 7.7 1区医学

Diabetes Pub Date : 2024-10-24 DOI: 10.2337/db24-0691

Siguo Feng, Qiuyang Zhang, Qing Liu, Chang Huang, Huiying Zhang, Fengsheng Wang, Yue Zhu, Qizhi Jian, Xue Chen, Qin Jiang, Biao Yan

{"title":"N 6-Methyladenosine demethylase FTO controls macrophage homeostasis in diabetic vasculopathy","authors":"Siguo Feng, Qiuyang Zhang, Qing Liu, Chang Huang, Huiying Zhang, Fengsheng Wang, Yue Zhu, Qizhi Jian, Xue Chen, Qin Jiang, Biao Yan","doi":"10.2337/db24-0691","DOIUrl":"https://doi.org/10.2337/db24-0691","url":null,"abstract":"Diabetic vasculopathy, encompassing complications such as diabetic retinopathy, represents a significant source of morbidity, with inflammation playing a pivotal role in the progression of these complications. This study investigates the influence of m6A modification and the m6A demethylase FTO on macrophage polarization and its subsequent effects on diabetic microvasculopathy. We found that diabetes induces a shift in macrophage polarization towards a pro-inflammatory M1 phenotype, which is associated with a reduction in m6A modification levels. Notably, FTO emerges as a critical regulator of m6A under diabetic conditions. In vitro experiments reveal that FTO not only modulates macrophage polarization but also mediates their interactions with vascular endothelial cells. In vivo experiments demonstrate that FTO deficiency exacerbates retinal inflammation and microvascular dysfunction in diabetic retinas. Mechanistically, FTO stabilizes mRNA through an m6A-YTHDF2-dependent pathway, thereby activating the PI3K/AKT signaling cascade. Collectively, these findings position FTO as a promising therapeutic target for the management of diabetic vascular complications.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"58 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Hyperketonemia on Myocardial Function in Patients with Heart Failure and Type 2 Diabetes 高酮血症对心力衰竭和 2 型糖尿病患者心肌功能的影响

IF 7.7 1区医学

Diabetes Pub Date : 2024-10-24 DOI: 10.2337/db24-0406

Carolina Solis-Herrera, Yuejuan Qin, Henri Honka, Eugenio Cersosimo, Curtis Triplitt, Sivaram Neppala, Jemena Rajan, Francisca M. Acosta, Alexander J. Moody, Patricio Iozzo, Peter Fox, Geoffrey Clarke, Ralph A. DeFronzo

{"title":"Effect of Hyperketonemia on Myocardial Function in Patients with Heart Failure and Type 2 Diabetes","authors":"Carolina Solis-Herrera, Yuejuan Qin, Henri Honka, Eugenio Cersosimo, Curtis Triplitt, Sivaram Neppala, Jemena Rajan, Francisca M. Acosta, Alexander J. Moody, Patricio Iozzo, Peter Fox, Geoffrey Clarke, Ralph A. DeFronzo","doi":"10.2337/db24-0406","DOIUrl":"https://doi.org/10.2337/db24-0406","url":null,"abstract":"We examined the effect of increased plasma ketones on left ventricular (LV) function, myocardial glucose uptake (MGU), and myocardial blood flow (MBF) in type 2 diabetes (T2DM) patients with heart failure (HF). Three groups (I,II,III) of T2DM (12 per group) with LV ejection fraction ≤50% received incremental infusions of β-OH-B for 3-6 hours to raise plasma β-OH-B concentration throughout the physiologic (Groups I and II) and pharmacologic (Group III) range. Cardiac MRI was performed at baseline and after each β-OH-B infusion to provide measures of cardiac function. On a separate day, Group II also received NaHCO3 infusion, thus serving as their own control for time, volume, and pH. Additionally, Group II underwent positron emission tomography study with 18F-fluoro-2-deoxyglucose to examine effect of hyperketonemia on MGU. Groups I, II, III achieved plasma β-OH-B levels of 0.7±0.3, 1.6±0.2, 3.2±0.2 mmol/L, respectively. Cardiac output, LVEF, and stroke volume increased significantly during β-OH-B infusion in Groups II (CO, 4.54 to 5.30; EF, 39.9 to 43.8; SV, 70.3 to 80.0) and III (CO, 5.93 to 7.16; EF, 41.1 to 47.5; SV, 89.0 to 108.4) and did not change with NaHCO3 infusion in Group II. The increase in LVEF was greatest in Group III (p&lt;0.001 vs Group II). MGU and MBF were not altered by β-OH-B. In T2DM patients with LVEF≤50%, increased plasma β-OH-B significantly increased LV function dose-dependently. Since MGU did not change, the myocardial benefit of β-OH-B resulted from providing an additional fuel for the heart without inhibiting MGU.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"97 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system 新型 NGF 递送系统介导糖尿病角膜病变中的长期神经再生

IF 7.7 1区医学

Diabetes Pub Date : 2024-10-24 DOI: 10.2337/db24-0393

Lin Cong, Benxiang Qi, Shijiu Chen, Ruiling Liu, Suxia Li, Qingjun Zhou, Yihai Cao, Bi Ning Zhang, Lixin Xie

{"title":"Long-term nerve regeneration in diabetic keratopathy mediated by a novel NGF delivery system","authors":"Lin Cong, Benxiang Qi, Shijiu Chen, Ruiling Liu, Suxia Li, Qingjun Zhou, Yihai Cao, Bi Ning Zhang, Lixin Xie","doi":"10.2337/db24-0393","DOIUrl":"https://doi.org/10.2337/db24-0393","url":null,"abstract":"Diabetic keratopathy (DK) is a common chronic metabolic disorder that causes ocular surface complications. Among various therapeutic approaches, local delivery of nerve growth factor (NGF) remains the most effective treatment for DK. However, achieving a sustained therapeutic effect with NGF and the frequent drug delivery burden remain challenging during clinical practice. Here, we developed a novel adeno-associated virus (AAV)-based NGF delivery system that achieved one-year-long-lasting effects by a single injection. We refined the corneal stromal injection technique, resulting in reduced corneal edema and improved AAV distribution homogeneity. AAV serotype AAV.rh10 exhibited high tropism and specificity to corneal nerves. A dose of 2×109 vector genomes (vg) was determined to achieve efficient Ngf gene expression without inducing corneal immune responses. Moreover, NGF protein was highly expressed in trigeminal ganglion (TG) through a retrograde transport mechanism, indicating the capacity for repairing corneal nerve damage both at the root and corneal nerve endings. In a mouse DK model, a single injection of AAV-Ngf into the corneal stroma led to marked corneal nerve regeneration for over 5 months. Together, we provide a novel therapeutic paradigm for long-term effective treatment of DK and this therapeutic approach is superior to current DK therapies.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"14 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induction of a Müller glial-specific protective pathway safeguards the retina from diabetes induced damage 诱导 Müller 神经胶质特异性保护途径，保护视网膜免受糖尿病引起的损伤

IF 7.7 1区医学

Diabetes Pub Date : 2024-10-24 DOI: 10.2337/db24-0199

Cheng-Hui Lin, Man-Ru Wu, Bogdan Tanasa, Praveen Prakhar, Boxiong Deng, Alexander E. Davis, Liang Li, Alexander Xia, Yang Shan, Patrice E. Fort, Sui Wang

{"title":"Induction of a Müller glial-specific protective pathway safeguards the retina from diabetes induced damage","authors":"Cheng-Hui Lin, Man-Ru Wu, Bogdan Tanasa, Praveen Prakhar, Boxiong Deng, Alexander E. Davis, Liang Li, Alexander Xia, Yang Shan, Patrice E. Fort, Sui Wang","doi":"10.2337/db24-0199","DOIUrl":"https://doi.org/10.2337/db24-0199","url":null,"abstract":"Diabetes can lead to cell-type-specific responses in the retina, including vascular lesions, glial dysfunction and neurodegeneration, all of which contribute to retinopathy. However, the molecular mechanisms underlying these cell type-specific responses, and the cell types that are sensitive to diabetes have not been fully elucidated. Employing single cell transcriptomics, we profiled the transcriptional changes induced by diabetes in different retinal cell types in rat models as the disease progressed. Rod photoreceptors, a subtype of amacrine interneurons, and Müller glia exhibited rapid responses to diabetes at the transcript levels. Genes associated with ion regulation were upregulated in all three cell types, suggesting a common response to diabetes. Furthermore, focused studies revealed that while Müller glia initially increased the expression of genes playing protective roles, they cannot sustain this beneficial effect. We explored one of the candidate protective genes, Zinc finger protein 36 homolog (Zfp36), and observed that depleting Zfp36 in rat Müller glial cells in vivo using AAV-based tools exacerbated diabetes-induced phenotypes, including glial reactivation, neurodegeneration, and vascular defects. Over-expression of Zfp36 slowed the development of these phenotypes. This work unveiled retinal cell types that are sensitive to diabetes and demonstrated that Müller glial cells can mount protective responses through Zfp36.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"1 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0