Diabetes最新文献

{"title":"Advances in Cell Replacement Therapies for Diabetes","authors":"Bernhard J. Hering, Michael R. Rickels, Melena D. Bellin, Jeffrey R. Millman, Alice A. Tomei, Andrés J. García, Haval Shirwan, Cherie L. Stabler, Minglin Ma, Peng Yi, Xunrong Luo, Qizhi Tang, Sabarinathan Ramachandran, Jose Oberholzer, Camillo Ricordi, Timothy J. Kieffer, A.M. James Shapiro","doi":"10.2337/db25-0037","DOIUrl":"https://doi.org/10.2337/db25-0037","url":null,"abstract":"Islet cell replacement therapies have evolved as a viable treatment option for type 1 diabetes complicated by problematic hypoglycemia and glycemic lability. Refinements of islet manufacturing, islet transplantation procedures, peritransplant recipient management, and immunosuppressive protocols allowed most recipients to achieve favorable outcomes. Subsequent phase 3 trials of transplantation of deceased donor islets documented the effectiveness of transplanted islets in restoring near-normoglycemia, glycemic stability, and protection from severe hypoglycemia, with an acceptable safety profile for the enrolled high-risk population. Health authorities in several countries have approved deceased donor islet transplantation for treating patients with type 1 diabetes and recurrent severe hypoglycemia. These achievements amplified academic and industry efforts to generate pluripotent stem cell–derived β-cells through directed differentiation for β-cell replacement. Preliminary results of ongoing clinical trials suggest that the transplantation of stem cell–derived β-cells can consistently restore insulin independence in immunosuppressed recipients with type 1 diabetes, thus signaling the profound progress made in generating an unlimited and a uniform supply of cells for transplant. Avoiding the risks of chronic immunosuppression represents the next frontier. Several strategies have entered or are approaching clinical investigation, including immune-isolating islets, engineering immune-privileged islet implantation sites, rendering islets immune evasive, and inducing immune tolerance in transplanted islets. Capitalizing on high-dimensional, multiomic technologies for deep profiling of graft-directed immunity and the fate of the graft will provide new insights that promise to translate into sustaining functional graft survival long-term. Leveraging these parallel progression paths will facilitate the wider clinical adoption of cell replacement therapies in diabetes care. Article Highlights Transplantation of deceased donor–derived primary human islets has restored near-normoglycemia and protection from severe hypoglycemia in immunosuppressed recipients with type 1 diabetes. Transplantation of embryonic stem cell–derived β-cells has restored insulin independence in immunosuppressed recipients with type 1 diabetes. Clinical trials are underway and planned to evaluate the safety and efficacy of transplantation of mature stem cell–derived β-cells with transient, local, minimal, and/or no-maintenance immunosuppression in recipients with type 1 diabetes. The high-dimensional, multiomic monitoring of immunity to transplanted islets and of the fate of the islet graft will faciliate the identification of determinants of sustained islet graft function and of patients most likely to benefit from cell replacement therapies.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"61 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920215","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}

{"title":"The Cardiovascular Repository for Type 1 Diabetes (CaRe-T1D): An NIDDK Initiative to Advance Understanding of Mechanisms Underlying Cardiovascular Disease in Type 1 Versus Type 2 Diabetes","authors":"Teresa L.Z. Jones, Irina Kusmartseva, Silvio Litovsky, Rahul Thakar, Amanda L. Posgai, Robert H. Eckel, Mark A. Atkinson","doi":"10.2337/db25-0017","DOIUrl":"https://doi.org/10.2337/db25-0017","url":null,"abstract":"Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in individuals with diabetes. Individuals with type 1 diabetes have a two- to fourfold higher risk of CVD in comparison with the general population, driven by an earlier onset and increased lifetime incidence of CVD events and mortality. Similarly, type 2 diabetes confers two- to threefold increased CVD risk, usually alongside metabolic syndrome, obesity, and hypertension. Despite advancements in methods for achieving glycemic control, the CVD burden remains disproportionately high in diabetes. The mechanisms driving elevated risk are complex and variably multifactorial, involving hyperglycemia, insulin resistance, dyslipidemia, inflammation, and a hypercoagulable state. Unfortunately, critical gaps in understanding persist on how these factors interact to promote CVD in type 1 versus type 2 diabetes, particularly across disease stages and age. Addressing these knowledge gaps is essential to developing targeted therapies that can effectively mitigate CVD risk. To meet this need, the National Institute of Diabetes and Digestive and Kidney Diseases, in partnership with the National Heart, Lung, and Blood Institute, recently formed the Cardiovascular Repository for Type 1 Diabetes (CaRe-T1D) program. Its mission is to elucidate the molecular and cellular pathways linking diabetes with CVD through the provision of high-quality human tissues for investigator-led analyses using cutting-edge technologies and collaborative data sharing to advance precision medicine and reduce the global burden of diabetes-associated cardiovascular complications. Article Highlights CaRe-T1D established a biorepository and scientific consortium to advance research on cardiovascular complications in diabetes. The goal is to determine how cardiovascular disease differs in type 1 versus type 2 diabetes. Heart, kidney, carotid and peripheral arteries, and blood from organ donors with type 1 diabetes, with type 2 diabetes, or without diabetes will be distributed to approved investigators to address the pathogenesis of diabetic cardiovascular disease. CaRe-T1D is a resource of human cardiovascular tissue and a database with the results from tissue analysis.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"28 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920240","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}

{"title":"Paradoxical maturity-onset diabetes of the young (MODY) arising from loss-of-function mutations in ATP-sensitive potassium channels","authors":"Rosa Scala, Yunpeng Li, Jian Gao, Nathan W. York, Ranjit Unnikrishnan, Ranjit Mohan Anjana, Viswanathan Mohan, Sundaramoorthy Gopi, Babu Kavitha, Venkatesan Radha, Colin G. Nichols","doi":"10.2337/db25-0110","DOIUrl":"https://doi.org/10.2337/db25-0110","url":null,"abstract":"Pancreatic β-cell KATP channel closure underlies electrical excitability and insulin release, but loss or inhibition of KATP channels can lead to paradoxical crossover from hyperinsulinism plus hypoglycemia, to glucose-intolerance or diabetes. We report genotype-phenotype information on a set of patients clinically diagnosed with maturity onset diabetes of the young (MODY), and carrying coding variants in the KATP regulatory subunit gene ABCC8. In contrast to the naïve prediction that diabetes should be associated with KATP gain-of-function (GOF, as in KATP-dependent neonatal diabetes) each mutation caused mild to severe loss-of-function (LOF), through distinct molecular mechanisms, suggesting the affected individuals may have crossed over to glucose intolerance from KATP channel LOF-dependent congenital hyperinsulinism (CHI). Our data provide definitive support for a paradoxical form of MODY in association with KATP channel LOF, genetically and mechanistically distinct from a late diagnosis of diabetes resulting from KATP GOF. To avoid confusion and inappropriate treatment efforts, we argue that diabetes driven by KATP-GOF and KATP-LOF mutations should be officially recognized as distinct diseases.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"284 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920115","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}

{"title":"Identifying four obesity axes through integrative multi-omics and imaging analysis","authors":"Chiemela S. Odoemelam, Afreen Naz, Marjola Thanaj, Elena P Sorokin, Brandon Whitcher, Naveed Sattar, Jimmy D Bell, E Louise Thomas, Madeleine Cule, Hanieh Yaghootkar","doi":"10.2337/db24-1103","DOIUrl":"https://doi.org/10.2337/db24-1103","url":null,"abstract":"We aimed to identify distinct axes of obesity using advanced MRI-derived phenotypes. We used 24 MRI-derived fat distribution and muscle volume measures (UK Biobank, n= 33,122) to construct obesity axes through principal component analysis (PCA). Genome-wide association studies were performed for each axis to uncover genetic factors, followed by pathway enrichment, genetic correlation, and Mendelian randomization analyses to investigate disease associations. Four primary obesity axes were identified: (1) General Obesity, reflecting higher fat accumulation in all regions (visceral, subcutaneous, and ectopic fat); (2) Muscle-Dominant, indicating greater muscle volume; (3) Peripheral Fat, associated with higher subcutaneous fat in abdominal and thigh regions; and (4) Lower Body Fat, characterized by increased lower-body subcutaneous fat and reduced ectopic fat. Each axis was associated with distinct genetic loci and pathways. For instance, the Lower Body Fat Axis was associated with RSPO3 and COBLL1 which are emerging as promising candidates for therapeutic targeting. Disease risks varied across axes: the General Obesity Axis correlated with higher risks of metabolic and cardiovascular diseases; the Lower Body Fat Axis appeared protective against type 2 diabetes and cardiovascular disease. This study highlights the heterogeneity of obesity through the identification of obesity axes and emphasizes the potential to extend beyond BMI in defining and treating obesity for obesity-related disease management.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"37 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920219","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}

{"title":"Analysis of multiple insulin actions in single muscle fibres from insulin resistant mice reveals selective defect in endogenous GLUT4 translocation","authors":"Sebastian Judge, Stewart WC Masson, Søren Madsen, Meg Potter, David E James, James G Burchfield, Alexis Diaz-Vegas","doi":"10.2337/db25-0022","DOIUrl":"https://doi.org/10.2337/db25-0022","url":null,"abstract":"Accurate measurement of GLUT4 translocation is crucial for understanding insulin resistance in skeletal muscle, a key factor in the development of metabolic diseases. However, current methods rely on overexpressed epitope-tagged GLUT4 constructs or indirect measurements, limiting their physiological relevance and applicability. To overcome these challenges, we developed an innovative high-sensitivity imaging-based method that enables the direct assessment of endogenous GLUT4 translocation in primary skeletal muscle fibres. This approach utilises antibodies targeting exofacial epitopes on native GLUT4. Our method allows multiplexed analysis of multiple insulin-sensitive processes, including transferrin receptor trafficking and FOXO nuclear exclusion, alongside mitochondrial oxidative stress. This comprehensive approach provides a unique opportunity to simultaneously assess insulin action across different signalling branches within individual muscle fibres. We validated this method across multiple inbred mouse strains and models of insulin resistance, including chronic insulin exposure, palmitate treatment, and high-fat diet-induced obesity. Notably, we identified a selective defect in GLUT4 trafficking in insulin-resistant muscle fibres, while other insulin-dependent processes remained intact. By offering a high-fidelity model that maintains physiological relevance, this novel approach represents a significant advancement in the study of skeletal muscle insulin resistance and provides a powerful tool for dissecting gene-environment interactions that underlpin metabolic disease.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"26 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920114","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}

{"title":"GENETIC VARIATION IN GCKR AND PNPLA3 REGULATE METABOLIC BALANCE ACROSS THE LIVER","authors":"Yunyun Ma, Shiqi Zuo, Therlinder Lo, David Phan, Tyler Finley, Adrienne Mackay, Enrique Trigo, Jaana A. Hartiala, Hooman Allayee, Anny H. Xiang, Thomas A. Buchanan, Richard M. Watanabe","doi":"10.2337/db24-0923","DOIUrl":"https://doi.org/10.2337/db24-0923","url":null,"abstract":"We tested genetic variants in GCK, GCKR, and PNPLA3 for association with type 2 diabetes-related phenotypes under the hypothesis they may regulate metabolic balance across the liver and contribute to hepatic steatosis and insulin resistance in a large sample of self-identified Mexican Americans from the BetaGene Study. We further tested whether interactions with dietary fructose and total sugar contributes to the observed associations. GCK rs1799831 was not associated with any type 2 diabetes-related phenotypes either alone or with any interaction tested. We replicated previous associations reported for GCKR rs780094 and PNPLA3 rs738409. We also show the interaction between GCKR rs780094 and dietary fructose is associated with both glucose effectiveness and glucose effectiveness at zero insulin, measures reflective of hepatic glucose uptake. We further show the interaction between GCKR rs780094 and PNPLA3 rs738409 is associated with type 2 diabetes-related traits, including insulin sensitivity. We conclude variations in GCKR and PNPLA3 and their interactions with each other and dietary fructose are partial determinants of hepatic fat, likely due to alterations in relative contributions of different metabolic pathways in the liver. These findings point to both GCKR and PNPLA3 as important therapeutic targets to mitigate hepatic metabolic dysfunction.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"141 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920116","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}

{"title":"Neuroprotective Effect of a Novel Soluble Guanylate Cyclase Activator (sGCa) Runcaciguat in Diabetes and Ischemic Retinopathy","authors":"Elia J. Duh, Zhenhua Xu, Hongkwan Cho, Shirley Wu, William Schubert, Carsten Terjung, Fabio Baschiera, Lingli Zhou, Lijuan Wu, Grace Lee, Yangyiran Xie, Qiaoyan Hui, James Guerra, Joseph Mertz, Khaled Nassar","doi":"10.2337/db24-0739","DOIUrl":"https://doi.org/10.2337/db24-0739","url":null,"abstract":"Oxidative stress has a major pathogenic role in diabetic retinopathy, and neuroretina dysfunction is recognized as an early and important problem. Soluble guanylate cyclase (sGC) has been implicated for its neuroprotective effects in the central nervous system, but its role in the retina remains unclear. Here we demonstrated expression of sGC subunits GUCY1A1 and GUCY1B1 in healthy human and rodent retina in vascular cells and neuronal elements including retinal ganglion cells, bipolar, and amacrine cells. We provided evidence using in vitro and in vivo studies that sGC function is impaired by oxidative stress-induced damage in retina. The sGC activator runcaciguat activated sGC in multiple retinal cell types and counteracted the inhibitory effect of damage induced by oxidative stress on the retina and retinal cells. In the rat retinal ischemia-reperfusion model, runcaciguat treatment improved neuroretinal and visual function as measured by electroretinography and optokinetic tracking and resulted in retinal morphologic improvement. In the STZ-induced diabetic rat model, runcaciguat significantly improved neuroretinal function and improved inner plexiform layer thickness. These studies suggest that sGC signaling is involved in neuroretinal function and vision and that diabetes negatively affects this pathway, supporting restoring sGC activation as a novel therapy for early DR.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"22 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920156","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}

{"title":"GLP-1-mediated targeting of inflammation corrects obesogenic memory in male mice","authors":"Stéphane Léon, Julie Benoit, Samantha Clark, Philippe Zizzari, Bin Yang, Isabelle Dugail, Fatiha Merabtene, Karine Clement, Louise Eygret, Nathalie Dupuy, Jean-Christophe Delpech, Moïra Rossitto, Matthias Mack, Thierry Lesté-Lasserre, Brian Finan, Daniela Cota, Carmelo Quarta","doi":"10.2337/db24-1071","DOIUrl":"https://doi.org/10.2337/db24-1071","url":null,"abstract":"Obesity-induced biological changes often persist after weight loss and are difficult to reverse, a phenomenon known as ‘obesogenic memory’. This enduring effect is associated with metabolic inflammation, particularly in adipose tissue. In this study, we characterise a mouse model of obesogenic memory and evaluate the efficacy of the unimolecular conjugate GLP-1/Dexa, which selectively and safely delivers the anti-inflammatory drug dexamethasone to GLP-1 receptor (GLP-1R)-expressing cells. We document that this precision pharmacological approach outperforms treatment with GLP-1 or dexamethasone alone, significantly reducing body weight, food intake, adiposity and markers of adipose tissue inflammation in male mice with obesogenic memory. In addition, we identify the CCR2/CCL2 inflammatory pathway as an important mediator of glucose intolerance and adipose tissue inflammation associated with obesogenic memory. Our findings suggest that targeting inflammation via GLP-1R signalling may be a promising therapeutic strategy to alleviate obesogenic memory and improve the long-term clinical management of metabolic diseases.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"39 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822768","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}

{"title":"BAP1 suppresses white adipose tissue browning and thermogenesis through deubiquitinating KDM1B","authors":"Pengchao Wang, Jingbo Zhu, Liuye Yang, Yilong Wang, Minglu Liang, Fengcen Li, Ze Wang, Kaiyuan Liu, Mingfa Ai, Dazhu Li, Kai Huang, Meng Du","doi":"10.2337/db24-1011","DOIUrl":"https://doi.org/10.2337/db24-1011","url":null,"abstract":"Obesity is a growing global health threat, and inducing browning of white adipose tissue (WAT) to increase energy expenditure has become an attractive strategy for treating obesity and related metabolic complications. BRCA1-associated protein 1 (BAP1), a ubiquitin C-terminal hydrolase (UCH) domain-containing deubiquitinase (DUB) expressed broadly across tissues, has previously been shown to play an important role in liver carbohydrate and lipid metabolism. However, its role in the browning of inguinal white adipose tissue (iWAT) has not been studied. Our study initially found that BAP1 expression was downregulated in cold-induced mouse iWAT but upregulated in obese conditions. Furthermore, overexpression of BAP1 in the inguinal fat tissue suppressed iWAT browning and thermogenesis. Mechanistically, we found that BAP1 interacts with KDM1B and stabilizes it through deubiquitination. Subsequently, KDM1B demethylates H3K4me1/2 modifications in proximity to thermogenesis-related genes, thereby inhibiting the expression of genes essential for browning. In summary, our study shows that BAP1 negatively regulates iWAT browning via a mechanism mediated by KDM1B.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"74 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819375","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}

{"title":"A Randomized-Controlled, Double-Masked Cross-Over Study of a GPR119 Agonist on Glucagon Counterregulation during Hypoglycemia in Type 1 Diabetes","authors":"Anika Bilal, Anna Casu, Fanchao Yi, Tumpa Dutta, Justine M. Mucinski, Gina Mercouffer, Martin C. Marak, Marcus Hompesch, David Kelley, Richard E. Pratley","doi":"10.2337/db25-0096","DOIUrl":"https://doi.org/10.2337/db25-0096","url":null,"abstract":"Activation of GPR119 receptors, expressed on enteroendocrine and pancreatic islet cells, augments glucagon counterregulatory responses to hypoglycemia in pre-clinical models. We hypothesized that MBX-2982, a GPR119 agonist, would augment counterregulatory responses to experimental hypoglycemia in participants with type 1 diabetes. To assess this, we designed a phase 2a double-masked, cross-over trial in 18 participants (20–60 years) with type 1 diabetes. Participants were randomized to treatment with 600 mg MBX-2982 or placebo daily for 14 days with a two-week washout between treatments. Counterregulatory responses to hypoglycemia during a hyperinsulinemic-hypoglycemic clamp and hormonal responses during a mixed meal test (MMT) were measured. The maximum glucagon response, glucagon area under the curve (AUC) and incremental AUC were not significantly different during MBX-2982 vs placebo treatment. MBX-2982 did not alter epinephrine, norepinephrine, pancreatic polypeptide, free fatty acid, or endogenous glucose production responses to hypoglycemia compared to placebo. However, glucagon-like peptide-1 (GLP-1) response during the MMT was 17% higher with MBX-2982 compared to placebo treatment. In conclusion, GPR119 activation with MBX-2982 did not improve counterregulatory responses to hypoglycemia in people with type 1 diabetes. Increases in GLP-1 during the MMT are consistent with GPR119 target engagement and the expected pharmacodynamic response from L-cells.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"27 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766534","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}