Journal of Diabetes Investigation最新文献

{"title":"Uhrf1 downregulation promotes β-cell dedifferentiation by decreasing Foxo1 expression in type 2 diabetes.","authors":"Lanfang Fu, Juyun Zhang, Zhu Lin, Xubiao Meng","doi":"10.1111/jdi.70082","DOIUrl":"https://doi.org/10.1111/jdi.70082","url":null,"abstract":"<p><strong>Background: </strong>Islet β-cell dedifferentiation is a major pathological mechanism of type 2 diabetes (T2D). Forkhead box o1 (Foxo1) is a master regulator of β-cell dedifferentiation. The mechanisms by which Foxo1 expression is regulated remain unexplored. Epigenetic modification is involved in the occurrence and development of T2D. Ubiquitin-like with PDH and ring finger domains 1 (Uhrf1), as an important epigenetic regulator, is associated with the maintenance of DNA methylation and histone modification.</p><p><strong>Purpose: </strong>This study aimed to discover whether Uhrf1 regulates Foxo1 expression and β-cell dedifferentiation of rat insulinoma (INS-1) cells.</p><p><strong>Methods: </strong>RT-qPCR and Western blot were performed to detect the levels of Uhrf1, Foxo1, β-cell dedifferentiation, and proliferation and apoptosis related indicators. ChIP-qPCR was used to analyze the relative lysine trimethylation at positions 4, 9, and 27 on histone H3 (H3K4/9/27me3) enrichment on the Foxo1 promoter. Dual-luciferase reporter assay was performed to assess the interaction between Uhrf1 and Foxo1. Finally, a diabetic rat model was established and the rat islet β-cells were isolated.</p><p><strong>Results: </strong>Glucolipotoxicity-induced β-cell dedifferentiation of INS-1 cells, which was restored after Uhrf1 overexpression. Mechanistically, Uhrf1 regulated the H3K4/9/27me3 of the Foxo1 promoter region. Besides, Foxo1 overexpression suppressed β-cell dedifferentiation of INS-1 cells. Moreover, islet β-cells isolated from diabetic model rats showed increased dedifferentiation.</p><p><strong>Conclusion: </strong>Uhrf1 knockdown promoted H3K27me3 and H3K9me3 and reduced H3K4me3 level in INS-1 cells, resulting in the downregulation of Foxo1 expression, thus promoting β-cell dedifferentiation.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of HbA1c variability and time-in-range fluctuations on large and small nerve fiber dysfunction in well-controlled type 2 diabetes: A prospective cohort observational study.","authors":"Yun-Ru Lai, Wen-Chan Chiu, Ben-Chung Cheng, I-Hsun Yu, Ting-Yin Lin, Hui-Ching Chiang, Chun-En Aurea Kuo, Cheng-Hsien Lu","doi":"10.1111/jdi.70079","DOIUrl":"https://doi.org/10.1111/jdi.70079","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Glycemic variability (GV) is a critical factor in the development of diabetic sensorimotor polyneuropathy (DSPN). This study aimed to evaluate the association of long-term GV, measured by glycated hemoglobin (HbA1c) average real variability (ARV), and short-term GV, assessed by time-in-range (TIR) ARV, with large and small nerve fiber dysfunction in individuals with well-controlled Type 2 Diabetes (T2D).</p><p><strong>Materials and methods: </strong>A prospective study conducted at a tertiary hospital in Taiwan included 82 T2D participants. Long-term GV was assessed using HbA1c ARV from visit-to-visit measurements at three-month intervals over 1 year. Short-term GV was evaluated as TIR ARV from seven-day fingerstick data collected quarterly. Large and small nerve functions were assessed using the Toronto Clinical Neuropathy Score (TCNS), nerve conduction studies, quantitative thermal testing, and Sudoscan.</p><p><strong>Results: </strong>Linear regression analysis adjusted for age, diabetes duration, and renal function revealed strong correlations between HbA1c ARV, TIR ARV, and diabetes duration. At baseline, high HbA1c ARV and TIR ARV groups exhibited higher TCNS and composite nerve conduction amplitude scores but lower cold detection thresholds compared to the low median groups. At one-year follow-up, TCNS significantly increased in the high HbA1c ARV (P = 0.001) and TIR ARV (P = 0.003) groups compared to the low median groups.</p><p><strong>Conclusions: </strong>Both long-term and short-term GV significantly contribute to small and large nerve fiber dysfunction in T2D, yielding similar neurological outcomes despite stable mean glucose levels. Combining GV minimization strategies with standard glycemic control may be essential in reducing DSPN risk.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144109321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastric filling ultrasound in assessing gastrointestinal motility in type 2 diabetic patients with neuropathy: A clinical study.","authors":"Juan Yan, Xiaoying Sun, Xiaoyan Liu, Xiaoming Li","doi":"10.1111/jdi.70059","DOIUrl":"https://doi.org/10.1111/jdi.70059","url":null,"abstract":"<p><strong>Aims: </strong>This study evaluates gastrointestinal motility dysfunction in type 2 diabetes patients with and without neuropathy compared to healthy individuals using gastric filling ultrasound.</p><p><strong>Materials and methods: </strong>We enrolled 210 participants: 50 healthy controls, 106 diabetic controls (without neuropathy), and 54 observation patients (with neuropathy). Gastric emptying times and fullness scores were measured at 30 and 60 min post-meal. Small intestinal transit rates were assessed at baseline and 60 min. Gastric capacity and wall thickness were evaluated by ultrasound, while motilin and glucagon levels were measured by ELISA.</p><p><strong>Results: </strong>The observation group showed significantly prolonged gastric emptying vs both control groups (30 min: 75.38 ± 13.49 vs 52.46 ± 11.37 vs 45.96 ± 12.85 min; 60 min: 122.53 ± 16.38 vs 84.27 ± 11.44 vs 75.12 ± 10.20 min; all P < 0.001). Gastric fullness scores exhibited similar progressive increases (30 min: 7.45 ± 0.66 vs 5.37 ± 0.75 vs 4.53 ± 0.69; 60 min: 6.84 ± 0.51 vs 4.56 ± 0.68 vs 3.72 ± 0.51; P < 0.001). Small intestinal transit was slowest in the observation group (baseline: 3.62 ± 0.21 vs 4.53 ± 0.36 vs 5.36 ± 0.25 cm/min; 60 min: 3.05 ± 0.15 vs 4.15 ± 0.50 vs 5.25 ± 0.31 cm/min; P < 0.05). The observation group had significantly reduced gastric capacity (714.68 ± 35.49 vs 875.25 ± 53.66 vs 923.63 ± 39.72 mL) and increased wall thickness (4.16 ± 0.55 vs 3.33 ± 0.42 vs 2.98 ± 0.26 cm) vs other groups (P < 0.001). Hormonal changes included lower motilin (28.44 ± 5.16 vs 45.67 ± 7.33 vs 53.71 ± 8.65 pg/mL) and higher glucagon (382.56 ± 23.62 vs 295.14 ± 11.55 vs 256.86 ± 27.90 pg/mL) in the observation group (P < 0.001).</p><p><strong>Conclusions: </strong>Gastric filling ultrasound demonstrates progressive gastrointestinal impairment from healthy individuals to diabetic patients, with the most severe dysfunction in neuropathic cases. These objective measures support regular gastrointestinal assessment in diabetes management, particularly for patients developing neuropathy.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Canagliflozin protects cardiovascular function in type 2 diabetic coronary artery disease by regulating natriuretic peptide B.","authors":"Jiarui Zhang, Lichenlu Huang, Yongqin Zheng, Ji Yang, Xiaopei Wu, Jundong He","doi":"10.1111/jdi.70056","DOIUrl":"https://doi.org/10.1111/jdi.70056","url":null,"abstract":"<p><strong>Background: </strong>Canagliflozin (Cana) has protected against diabetes-related cardiovascular disease. This study was intended to explore the effect and molecular mechanism of Cana on cardiovascular protection in type 2 diabetic coronary atherosclerotic heart disease (CAD).</p><p><strong>Materials and methods: </strong>We constructed a rat model of type 2 diabetic CAD and examined its physiological and biochemical indices before and after Cana treatment. Next-generation transcriptome sequencing was performed on rat cardiac tissue. Various functional and molecular experiments involving Cana treatment and the natriuretic peptide B (NPPB) gene were performed on human cardiomyocytes (AC16 cells).</p><p><strong>Results: </strong>The physiological, biochemical, and imaging parameters of the model rats were abnormal. Cana treatment reversed these injuries. In all, 369 differentially expressed genes were discovered by next-generation transcriptome sequencing; NPPB was identified as the target gene. Cana treatment significantly improved the function of AC16 cells treated with high glucose and significantly upregulated the expression level of the NPPB gene. The NPPB gene significantly increased the viability of AC16 cells and significantly decreased the apoptosis rate and reactive oxygen species (ROS) level. In addition, NPPB significantly upregulated the expression of B-cell lymphoma 2 (Bcl-2) and downregulated the expression of Bcl-2 associated X protein (Bax). Cana treatment further improved these cellular functions and protein expression levels. Furthermore, the NPPB gene significantly upregulated protein kinase 1-α (PKG1α) expression level and Cana treatment enhanced the regulatory effect of NPPB on PKG1α.</p><p><strong>Conclusions: </strong>The cardiovascular protective effect of Cana in diabetes mellitus was mediated by upregulating the expression of NPPB and upregulating the level of PKG1α, which in turn regulated the viability, apoptosis rate, and ROS level of AC16 cells.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commentary on \"Prevalence, incidence, and risk factors of diabetic retinopathy and macular edema in patients with early and late-onset type 2 diabetes mellitus\".","authors":"Fatemeh Rasulpur, Mohammad Ranaee, Mohammad Barary, Sahar Sadr Moharerpour, Soheil Ebrahimpour","doi":"10.1111/jdi.70076","DOIUrl":"https://doi.org/10.1111/jdi.70076","url":null,"abstract":"","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conundrum and chances of diabetes management in the Western Pacific Region: A narrative review.","authors":"Yerin Hwang, Hyunmin Lee, Moon-Kyu Lee","doi":"10.1111/jdi.70053","DOIUrl":"https://doi.org/10.1111/jdi.70053","url":null,"abstract":"<p><p>The prevalence of diabetes is increasing globally, and glucose management is essential for the treatment of diabetes. Most guidelines recommend early intensive therapy and individualized approaches. Although many countries have implemented various guidelines and educational programs to enhance glucose management, the target achievement rate still remains very low. Studies from several countries and regions have identified various factors that influence blood glucose management, either positively or negatively. These factors have been comprehensively incorporated into guidelines to assist people with diabetes and healthcare professionals in following them and/or developing additional guidelines through further research. We and others have suggested that diverse factors should be considered-including comorbidities, age, complications, life expectancy, and pathophysiologic characteristics, such as ethnic differences in insulin sensitivity and secretion. The Western Pacific (WP) region, comprising countries with significant cultural and racial diversity, necessitates customized programs and community-based management strategies. In this review, we present specific challenges and opportunities for diabetes management identified through a systematic review of the literature from the WP region, along with those common to other regions. To improve healthcare policy and management in the WP region, it is essential to address regional characteristics and the factors that act as either barriers or facilitators to develop strategies for early intensive and individualized therapeutic approaches. Moreover, additional studies on diabetes pathophysiology and management-including pharmacotherapy-are urgently needed.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of lifestyle on diabetic nephropathy in aged 18-64 years: A population-based cross-sectional analysis from NHANES 2007-2018.","authors":"Zhijun Zhang, Zhaoyinling Wei, Ling Gao","doi":"10.1111/jdi.70069","DOIUrl":"https://doi.org/10.1111/jdi.70069","url":null,"abstract":"<p><strong>Background: </strong>The relationship between lifestyle and overall health has garnered significant attention. This study aimed to evaluate the association between lifestyle factors and diabetic nephropathy (DN) in adults aged 18-64 years.</p><p><strong>Materials and methods: </strong>We conducted a cross-sectional study involving 2,389 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The use of the Healthy Eating Index (HEI), Metabolic Equivalent of Task (MET), sleeping duration, smoking, and drinking status as indicators to assess lifestyle. Logistic regression analyses and restricted cubic splines were used to analyze the results. A subgroup analysis was performed to identify any variations.</p><p><strong>Results: </strong>Logistic regression analysis indicates that poor HEI and sleep duration but not physical activity are associated with an increased risk of DN. Subgroup analyses revealed significant interactions between HEI and age, blood pressure, HbA1c, and lipid control; MET interacted with blood pressure and HbA1c control; Sleeping duration interacted with age, smoking, blood pressure, HbA1c, and lipid control; Smoking interacted with age, blood pressure control, and lipid control; Drinking interacted with blood pressure control. Moreover, restricted cubic splines indicated that with increasing HEI, the prevalence of DN tended to decrease. However, the associations between the other two lifestyle factors (MET level and sleeping duration) and DN were all U-shaped.</p><p><strong>Conclusions: </strong>Lifestyle factors are closely associated with diabetic nephropathy. Both unhealthy eating habits and inadequate or excessive sleeping duration and physical activity contribute to an increased risk of diabetic nephropathy, whereas no statistically significant association is observed in smoking and drinking.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoglycemic timeslots after hospital discharge in patients with diabetes on multiple daily insulin injection: Dose of Insulin CHanged According to the Reported Glucose by Libre Pro (DISCHARGe study).","authors":"Manabu Saito, Hiroshi Uchino, Ayako Fuchigami, Genki Sato, Masahiko Miyagi, Takahisa Hirose","doi":"10.1111/jdi.70065","DOIUrl":"https://doi.org/10.1111/jdi.70065","url":null,"abstract":"<p><strong>Introduction: </strong>Insulin improves clinical outcomes in hospitalized patients; however, hypoglycemia hinders discharge transition in patients with insulin-treated diabetes. Studies on hypoglycemic timeslots, rates, and risk factors during discharge transition are lacking.</p><p><strong>Materials and methods: </strong>Fifteen patients with type 2 diabetes (T2D) receiving multiple daily insulin (MDI) injections participated. Glucose variability metrics and hypoglycemia were monitored using a continuous glucose monitoring system starting a day pre-discharge through 13 days of discharge transition. Hypoglycemia was analyzed chronobiologically using Cosinor analysis. Anthropometric measurements, C-peptide, insulin dose, and glucagon were assessed.</p><p><strong>Results: </strong>The mean patient age was 52.7 ± 12.6 years; 13/15 were male; body mass index was 28.1 ± 5.9 kg/m², T2D duration was 8.6 ± 8.8 years, HbA1c was 12.4 ± 2.5%, and total daily insulin dose averaged 36.6 ± 15.1 units and hospitalization lasted 13.1 ± 2.3 days. Time in range decreased post-discharge. Time below range increased from 7.0% at discharge to 17.6% by the study end (manova, P < 0.001). Hypoglycemic events peaked post-breakfast, with the highest amplitude (42 points) recorded at 12:00. The highest and lowest numbers of hypoglycemia occurred at 12:00 and 17:30, respectively. However, the highest hypoglycemic timeslot (11:00-12:00) was not significantly associated with clinical and biochemical parameters.</p><p><strong>Conclusions: </strong>The chronobiology of hypoglycemia exists during the discharge transition in patients with MDI-treated T2D. Hypoglycemia frequency and severity peaked pre-lunch, reached a nadir at 17:30, and exaggerated post-discharge, emphasizing the need for pre-breakfast insulin dose reductions on the discharge day.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in cause of death and age at death between people with and without diabetes over 10 years (2010-2020): A cross-sectional study in Japan.","authors":"Hirofumi Sugimoto, Noriko Ihana-Sugiyama, Takehiro Sugiyama, Noriko Kodani, Ryotaro Bouchi, Mitsuru Ohsugi, Kohjiro Ueki, Hiroshi Kajio","doi":"10.1111/jdi.70067","DOIUrl":"https://doi.org/10.1111/jdi.70067","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Investigating the causes of death in individuals with diabetes compared with those without is essential for understanding diabetes care. However, methods for identifying individuals with diabetes within populations vary. We conducted a comparison of these groups under identical conditions, analyzing differences in causes and age at death, and assessing how different identification methods influence these outcomes.</p><p><strong>Materials and methods: </strong>This study used the clinical records of inpatients who died at the National Center for Global Health and Medicine from September 1, 2010, to December 31, 2020. Individuals with or without diabetes were defined using prescriptions and laboratory data. The cause of death was determined by the name of the primary illness provided by the attending physician at the time of death. Individuals with diabetes were stratified by different definitions, and their age at death was compared.</p><p><strong>Results: </strong>In Individuals with diabetes, males accounted for 67.6%, and in those without diabetes, 57.0%. The mean age at death was 75.0 ± 11.8 and 73.8 ± 16.0 years, respectively. Malignant neoplasia was the most common cause of death in both groups, with a higher frequency in individuals with diabetes (36.9% vs 31.0%). Age at death of individuals with diabetes differed by up to 1.5 years, depending on the definitions.</p><p><strong>Conclusions: </strong>Direct comparisons suggested that malignant neoplasia was the leading cause of death, and individuals with diabetes had a higher mean age at death. The method used to identify diabetes influenced these outcomes, emphasizing the importance of careful consideration in mortality studies.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipocyte exosome miR-4472 inhibits glucose uptake in skeletal muscle through downregulation of MEF2D.","authors":"Chaoyue Sun, Xin Wen, Xiaolong Chu, Fangyuan Yuan, Yao Chen, Chaoling Peng, Meiyu Qian, Jin Mei, Juan Wang, Yidan Jiang, Shibo Xu, Cuizhe Wang, Wei Li, Jun Zhang","doi":"10.1111/jdi.70054","DOIUrl":"https://doi.org/10.1111/jdi.70054","url":null,"abstract":"<p><strong>Aims/introduction: </strong>Previous studies have found that miR-4472 is overexpressed in the serum of individuals with obesity and type 2 diabetes mellitus (T2DM), which may participate in the process of obesity-induced T2DM. However, a role for miR-4472 in the process has not been demonstrated. Here, we aim to investigate whether the increased content of miR-4472 in adipose tissue derived from exosomes inhibits glucose uptake in skeletal muscle by downregulating the expression of its target gene.</p><p><strong>Materials and methods: </strong>In vitro C2C12 and 3T3-L1 cells, and in vivo diet-induced obesity mouse models and AT-Dicer KO mice were used to assess the impact of miR-4472 on glucose uptake and insulin sensitivity. We also evaluated the effects of serum exosomes from normal and obese individuals on insulin sensitivity in mice and the expression of miR-4472 and target genes in skeletal muscle.</p><p><strong>Results: </strong>miR-4472 exhibits a strong positive correlation with BMI, waist circumference, hip circumference, and FPG. The content of miR-4472 derived from adipose tissue exosomes increases in the circulation in a state of obesity, which can induce insulin resistance by targeting the expression of MEF2D/GLUT4, inhibiting the glucose consumption and uptake ability of skeletal muscle cells. Both exosome inhibitors and miR-4472 inhibitors can reverse the inhibitory effect of miR-4472 on MEF2D/GLUT4 expression and glucose intake and uptake ability. Additionally, they can improve insulin resistance caused by increased miR-4472 levels in mice with obesity.</p><p><strong>Conclusions: </strong>Adipocyte exosome miR-4472 inhibits glucose uptake in skeletal muscle through downregulating the expression of MEF2D/GLUT4.</p>","PeriodicalId":190,"journal":{"name":"Journal of Diabetes Investigation","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}