Nature metabolism最新文献_第4页

Exercise inhibits cellular senescence in pancreatic islets 运动可抑制胰岛细胞衰老

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-24 DOI: 10.1038/s42255-024-01132-6

Gregory D. Cartee

引用次数: 0

Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence 运动可激活小鼠和人类胰岛中的 AMPK，从而减少衰老

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-24 DOI: 10.1038/s42255-024-01130-8

Priscila Carapeto, Kanako Iwasaki, Francesko Hela, Jiho Kahng, Ana B. Alves-Wagner, Roeland J. W. Middelbeek, Michael F. Hirshman, Guy A. Rutter, Laurie J. Goodyear, Cristina Aguayo-Mazzucato

{"title":"Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence","authors":"Priscila Carapeto, Kanako Iwasaki, Francesko Hela, Jiho Kahng, Ana B. Alves-Wagner, Roeland J. W. Middelbeek, Michael F. Hirshman, Guy A. Rutter, Laurie J. Goodyear, Cristina Aguayo-Mazzucato","doi":"10.1038/s42255-024-01130-8","DOIUrl":"10.1038/s42255-024-01130-8","url":null,"abstract":"Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence. In vivo and in vitro experiments revealed that this effect is mediated, at least in part, by training-induced increases in serum glucagon, leading to activation of 5′-AMP-activated protein kinase (AMPK) signalling in β-cells. AMPK activation resulted in the nuclear translocation of NRF2 and decreased expression of senescence markers and effectors. Remarkably, human islets from male and female donors with T2DM treated with serum collected after a 10-week endurance exercise training programme showed a significant decrease in the levels of senescence markers. These findings indicate that exercise training decreases senescence in pancreatic islets, offering promising therapeutic implications for T2DM. Exercise training decreases pancreatic islet senescence through glucagon and AMPK signalling in mouse and human islets, which could have implications for T2DM therapeutics.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 10","pages":"1976-1990"},"PeriodicalIF":18.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313708","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

Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes 1 型糖尿病患者低血糖诱导的胰高血糖素分泌受损的原因是 β 细胞与 δ 细胞间电偶联的缺失

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-23 DOI: 10.1038/s42255-024-01139-z

Thomas G. Hill, Rui Gao, Anna Benrick, Lakshmi Kothegala, Nils Rorsman, Cristiano Santos, Samuel Acreman, Linford J. Briant, Haiqiang Dou, Nikhil R. Gandasi, Claudia Guida, Elizabeth Haythorne, Marsha Wallace, Jakob G. Knudsen, Caroline Miranda, Johan Tolö, Anne Clark, Lucy Davison, Joachim Størling, Andrei Tarasov, Frances M. Ashcroft, Patrik Rorsman, Quan Zhang

{"title":"Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes","authors":"Thomas G. Hill, Rui Gao, Anna Benrick, Lakshmi Kothegala, Nils Rorsman, Cristiano Santos, Samuel Acreman, Linford J. Briant, Haiqiang Dou, Nikhil R. Gandasi, Claudia Guida, Elizabeth Haythorne, Marsha Wallace, Jakob G. Knudsen, Caroline Miranda, Johan Tolö, Anne Clark, Lucy Davison, Joachim Størling, Andrei Tarasov, Frances M. Ashcroft, Patrik Rorsman, Quan Zhang","doi":"10.1038/s42255-024-01139-z","DOIUrl":"https://doi.org/10.1038/s42255-024-01139-z","url":null,"abstract":"Diabetes mellitus involves both insufficient insulin secretion and dysregulation of glucagon secretion1. In healthy people, a fall in plasma glucose stimulates glucagon release and thereby increases counter-regulatory hepatic glucose production. This response is absent in many patients with type-1 diabetes (T1D)2, which predisposes to severe hypoglycaemia that may be fatal and accounts for up to 10% of the mortality in patients with T1D3. In rats with chemically induced or autoimmune diabetes, counter-regulatory glucagon secretion can be restored by SSTR antagonists4,5,6,7 but both the underlying cellular mechanism and whether it can be extended to humans remain unestablished. Here, we show that glucagon secretion is not stimulated by low glucose in isolated human islets from donors with T1D, a defect recapitulated in non-obese diabetic mice with T1D. This occurs because of hypersecretion of somatostatin, leading to aberrant paracrine inhibition of glucagon secretion. Normally, KATP channel-dependent hyperpolarization of β-cells at low glucose extends into the δ-cells through gap junctions, culminating in suppression of action potential firing and inhibition of somatostatin secretion. This ‘electric brake’ is lost following autoimmune destruction of the β-cells, resulting in impaired counter-regulation. This scenario accounts for the clinical observation that residual β-cell function correlates with reduced hypoglycaemia risk8.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"17 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276825","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

Reply to: Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults 答复中国成年人的牛奶摄入量、乳糖不耐受性与 2 型糖尿病风险

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-18 DOI: 10.1038/s42255-024-01129-1

Kai Luo, Yanbo Zhang, Robert C. Kaplan, Qibin Qi

引用次数: 0

Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults 中国成年人的牛奶摄入量、乳糖不耐受性与 2 型糖尿病风险

IF 20.8 1区医学

Nature metabolism Pub Date : 2024-09-18 DOI: 10.1038/s42255-024-01128-2

Maria G. Kakkoura, Robin G. Walters, Robert Clarke, Zhengming Chen, Huaidong Du

{"title":"Milk intake, lactase non-persistence and type 2 diabetes risk in Chinese adults","authors":"Maria G. Kakkoura, Robin G. Walters, Robert Clarke, Zhengming Chen, Huaidong Du","doi":"10.1038/s42255-024-01128-2","DOIUrl":"https://doi.org/10.1038/s42255-024-01128-2","url":null,"abstract":"arising from K. Luo et al. Nature Metabolism https://doi.org/10.1038/s42255-023-00961-1 (2024)In the 2024 January issue of Nature Metabolism, Luo et al.1 reported an inverse association between milk intake and risk of type 2 diabetes (T2D) among individuals who were lactase non-persistent (LNP), as determined by the lactase (LCT) rs4988235 homozygous GG genotype. The authors also reported inverse cross-sectional associations of milk intake with several T2D-related metabolic traits, including body mass index (BMI) and waist circumference (WC) in LNP individuals. However, in their analyses, no adjustments for BMI/WC were done in assessing the association between milk intake and T2D risk, which may lead to biased results. Given the established causal relevance of adiposity for incident T2D2,3 and the observed inverse associations of milk intake with adiposity in the study population, it is therefore important to establish whether the associations of milk consumption, milk-associated gut bacteria and milk-associated metabolites with T2D risk are confounded, or mediated, by BMI/WC in the paper by Luo et al.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"9 1","pages":""},"PeriodicalIF":20.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236226","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

Publisher Correction: Efferocytosis drives a tryptophan metabolism pathway in macrophages to promote tissue resolution. 出版商更正：吞噬作用驱动巨噬细胞中的色氨酸代谢途径，从而促进组织溶解。

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-16 DOI: 10.1038/s42255-024-01142-4

Santosh R Sukka, Patrick B Ampomah, Lancia N F Darville, David Ngai, Xiaobo Wang, George Kuriakose, Yuling Xiao, Jinjun Shi, John M Koomen, Robert H McCusker, Ira Tabas

引用次数: 0

Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency 在线粒体上组织功能性糖酵解代谢子以提高代谢效率

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-11 DOI: 10.1038/s42255-024-01121-9

Haoming Wang, John W. Vant, Andrew Zhang, Richard G. Sanchez, Youjun Wu, Mary L. Micou, Vincent Luczak, Zachary Whiddon, Natasha M. Carlson, Seungyoon B. Yu, Mirna Jabbo, Seokjun Yoon, Ahmed A. Abushawish, Majid Ghassemian, Takeya Masubuchi, Quan Gan, Shigeki Watanabe, Eric R. Griffis, Marc Hammarlund, Abhishek Singharoy, Gulcin Pekkurnaz

{"title":"Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency","authors":"Haoming Wang, John W. Vant, Andrew Zhang, Richard G. Sanchez, Youjun Wu, Mary L. Micou, Vincent Luczak, Zachary Whiddon, Natasha M. Carlson, Seungyoon B. Yu, Mirna Jabbo, Seokjun Yoon, Ahmed A. Abushawish, Majid Ghassemian, Takeya Masubuchi, Quan Gan, Shigeki Watanabe, Eric R. Griffis, Marc Hammarlund, Abhishek Singharoy, Gulcin Pekkurnaz","doi":"10.1038/s42255-024-01121-9","DOIUrl":"10.1038/s42255-024-01121-9","url":null,"abstract":"Glucose, the primary cellular energy source, is metabolized through glycolysis initiated by the rate-limiting enzyme hexokinase (HK). In energy-demanding tissues like the brain, HK1 is the dominant isoform, primarily localized on mitochondria, and is crucial for efficient glycolysis–oxidative phosphorylation coupling and optimal energy generation. This study unveils a unique mechanism regulating HK1 activity, glycolysis and the dynamics of mitochondrial coupling, mediated by the metabolic sensor enzyme O-GlcNAc transferase (OGT). OGT catalyses reversible O-GlcNAcylation, a post-translational modification influenced by glucose flux. Elevated OGT activity induces dynamic O-GlcNAcylation of the regulatory domain of HK1, subsequently promoting the assembly of the glycolytic metabolon on the outer mitochondrial membrane. This modification enhances the mitochondrial association with HK1, orchestrating glycolytic and mitochondrial ATP production. Mutation in HK1’s O-GlcNAcylation site reduces ATP generation in multiple cell types, specifically affecting metabolic efficiency in neurons. This study reveals a previously unappreciated pathway that links neuronal metabolism and mitochondrial function through OGT and the formation of the glycolytic metabolon, providing potential strategies for tackling metabolic and neurological disorders. Wang et al. show how glucose sensing via O-GlcNAcylation drives the assembly of a glycolytic metabolon on the mitochondrial surface to couple metabolic efficiency with neuronal activity.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 9","pages":"1712-1735"},"PeriodicalIF":18.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142166288","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

O-GlcNAc transferase regulates glycolytic metabolon formation on mitochondria to enhance ATP production O-GlcNAc 转移酶调节线粒体上糖酵解代谢物的形成，以提高 ATP 的产生

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-11 DOI: 10.1038/s42255-024-01120-w

引用次数: 0

Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity 多年耐力运动训练重塑超重或肥胖成人的腹部皮下脂肪组织

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-10 DOI: 10.1038/s42255-024-01103-x

Cheehoon Ahn, Tao Zhang, Gayoung Yang, Thomas Rode, Pallavi Varshney, Sophia J. Ghayur, Olivia K. Chugh, Hui Jiang, Jeffrey F. Horowitz

{"title":"Years of endurance exercise training remodel abdominal subcutaneous adipose tissue in adults with overweight or obesity","authors":"Cheehoon Ahn, Tao Zhang, Gayoung Yang, Thomas Rode, Pallavi Varshney, Sophia J. Ghayur, Olivia K. Chugh, Hui Jiang, Jeffrey F. Horowitz","doi":"10.1038/s42255-024-01103-x","DOIUrl":"10.1038/s42255-024-01103-x","url":null,"abstract":"Abnormalities in the structure and metabolic function of abdominal subcutaneous adipose tissue (aSAT) underlie many obesity-related health complications. Endurance exercise improves cardiometabolic health in adults with overweight or obesity, but the effects of endurance training on aSAT are unclear. We included male and female participants who were regular exercisers with overweight or obesity who exercised for >2 years, and cross-sectionally compared them with well-matched non-exercisers with overweight or obesity. Here we show aSAT from exercisers has a higher capillary density, lower Col6a abundance and fewer macrophages compared with non-exercisers. This is accompanied by a greater abundance of angiogenic, ribosomal, mitochondrial and lipogenic proteins. The abundance of phosphoproteins involved in protein translation, lipogenesis and direct regulation of transcripts is also greater in aSAT collected from exercisers. Exploratory ex vivo experiments demonstrate greater angiogenic capacity and higher lipid-storage capacity in samples cultured from aSAT collected from exercisers versus non-exercisers. Regular exercise may play a role in remodelling aSAT structure and proteomic profile in ways that may contribute to preserved cardiometabolic health. Adults with overweight or obesity who exercise regularly for at least 2 years exhibit distinct structural and proteomic characteristics in abdominal subcutaneous adipose tissue that may contribute to better cardiometabolic health outcomes.","PeriodicalId":19038,"journal":{"name":"Nature metabolism","volume":"6 9","pages":"1819-1836"},"PeriodicalIF":18.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160375","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 exercise training has positive effects on adipose tissue in overweight or obesity 长期运动训练对超重或肥胖症患者的脂肪组织有积极影响

IF 18.9 1区医学

Nature metabolism Pub Date : 2024-09-10 DOI: 10.1038/s42255-024-01102-y

引用次数: 0