Nature Reviews Endocrinology最新文献

Obesity induces systemic insulin resistance via endothelium-specific insulin receptor inhibition

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-26 DOI: 10.1038/s41574-025-01097-w

Olivia Tysoe

{"title":"Obesity induces systemic insulin resistance via endothelium-specific insulin receptor inhibition","authors":"Olivia Tysoe","doi":"10.1038/s41574-025-01097-w","DOIUrl":"https://doi.org/10.1038/s41574-025-01097-w","url":null,"abstract":"Insulin resistance is a key component of the pathogenesis and progression of obesity-associated type 2 diabetes mellitus (T2DM). The insulin receptor is expressed in endothelial cells and insulin acts on blood vessels to increase blood flow to metabolic tissues. Endothelial insulin resistance was already known to be reduced in people with T2DM compared with healthy individuals, but the mechanisms of this insulin resistance and its contribution to T2DM development were unclear. Now, a paper in Science has determined that the peptide hormone adrenomedullin has a role in inducing vascular insulin resistance in the context of obesity.Adrenomedullin was found to inhibit insulin signalling, thereby preventing insulin-induced eNOS phosphorylation, a process that leads to vasodilation. Under healthy conditions, this vasodilation increases blood perfusion of metabolic tissues such as the skeletal muscle, adipose tissue and liver, enabling increased delivery of oxygen and nutrients. Inhibition of insulin signalling was mediated by the G protein subunit Gαs and protein kinase A (PKA), which increased activity of PTP1B, a key regulator of insulin sensitivity, via insulin receptor dephosphorylation. Knockout of adrenomedullin, knockdown of Gαs or chemical inhibition of PKA all led to increased insulin receptor phosphorylation and subsequent increased insulin signalling.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"12 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495377","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

Bone and muscle crosstalk in ageing and disease

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-26 DOI: 10.1038/s41574-025-01088-x

Ben Kirk, Giovanni Lombardi, Gustavo Duque

{"title":"Bone and muscle crosstalk in ageing and disease","authors":"Ben Kirk, Giovanni Lombardi, Gustavo Duque","doi":"10.1038/s41574-025-01088-x","DOIUrl":"https://doi.org/10.1038/s41574-025-01088-x","url":null,"abstract":"Interorgan communication between bone and skeletal muscle is central to human health. A dysregulation of bone–muscle crosstalk is implicated in several age-related diseases. Ageing-associated changes in endocrine, inflammatory, nutritional and biomechanical stimuli can influence the differentiation capacity, function and survival of mesenchymal stem cells and bone-forming and muscle-forming cells. Consequently, the secretome phenotype of bone and muscle cells is altered, leading to impaired crosstalk and, ultimately, catabolism of both tissues. Adipose tissue acts as a third player in the bone–muscle interaction by secreting factors that affect bone and muscle cells. Physical exercise remains the key biological stimulus for bone–muscle crosstalk, either directly via the release of cytokines from bone, muscle or adipocytes, or indirectly through extracellular vesicles. Overall, bone–muscle crosstalk is considered an inherent process necessary to maintain the structure and function of both tissues across the life cycle. This Review summarizes the latest biomedical advances in bone–muscle crosstalk as it pertains to human ageing and disease. We also outline future research priorities to accommodate the understanding of this rapidly emerging field.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"27 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495379","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

Sexual dimorphism in pituitary neuroendocrine tumours

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-25 DOI: 10.1038/s41574-025-01096-x

Shaojian Lin, Jun Li, Zhe Bao Wu

引用次数: 0

Neutrophils might link intestinal damage to retinopathy in type 2 diabetes mellitus

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-24 DOI: 10.1038/s41574-025-01094-z

Senegal Carty

引用次数: 0

Engineering adipocytes for cancer treatment

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-20 DOI: 10.1038/s41574-025-01095-y

Claire Greenhill

引用次数: 0

The enduring relevance of the Randle cycle

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-19 DOI: 10.1038/s41574-025-01092-1

Azariyas A. Challa

{"title":"The enduring relevance of the Randle cycle","authors":"Azariyas A. Challa","doi":"10.1038/s41574-025-01092-1","DOIUrl":"https://doi.org/10.1038/s41574-025-01092-1","url":null,"abstract":"In people with diabetes mellitus, the heart is metabolically characterized by the excessive use of fatty acids and diminished oxidation of glucose. These changes are implicated in decreased cardiac efficiency, vulnerability to ischaemic insults and an increased risk of heart failure. Interestingly, these alterations have been observed even in the absence of any impairments in cardiac insulin signalling, which suggests a role for direct substrate competition — a concept that was first described by Philip Randle and colleagues in a 1963 Lancet paper. The principle of reciprocal substrate competition between fatty acids and glucose for ATP generation laid out in this landmark publication formed the basis for our present understanding of cardiac metabolism in physiology and in response to metabolic stress.Randle et al. showed that provision of exogenous fatty acids to isolated heart and diaphragm preparations or the presence of increased circulating levels of nonesterified fatty acids following adipose tissue lipolysis promotes fatty acid oxidation (FAO) and inhibits glucose utilization independent of hormonal control. The authors proposed that inhibition of pyruvate dehydrogenase (PDH; the mitochondrial enzyme that catalyses the conversion of pyruvate to acetyl-CoA) by acetyl-CoA derived from FAO is the primary mechanism by which fatty acids inhibit glucose utilization. By contrast, when glucose is abundant, utilization of glucose in adipose tissue inhibits lipolysis and the release of nonesterified fatty acids, which results in reduced fatty acid utilization by oxidative tissues and hence completes a ‘glucose–fatty acid cycle’ (now better known as the Randle cycle).","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"24 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443174","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

The study that pioneered islet isolation techniques

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-02-18 DOI: 10.1038/s41574-025-01093-0

Rula Bany Bakar

{"title":"The study that pioneered islet isolation techniques","authors":"Rula Bany Bakar","doi":"10.1038/s41574-025-01093-0","DOIUrl":"https://doi.org/10.1038/s41574-025-01093-0","url":null,"abstract":"In rodents, the endocrine pancreas consists of islets of Langerhans scattered throughout the exocrine acinar tissue and accounts for a minor fraction of the organ’s total volume. This anatomical configuration, combined with the small size of the islets and the fact that they are embedded within enzyme-rich exocrine tissue, has historically made isolating intact and functional islets a considerable challenge, particularly for metabolic studies that require pure islet tissue.Early efforts in the 1960s used free-hand microdissection to isolate small numbers of islets from rodent pancreas tissue and primarily targeted hypertrophic islets in obese rodents, in which surface islets are fairly accessible. Another method involved inducing pancreatic atrophy by ligating one of the main pancreatic ducts to facilitate islet dissection. However, these techniques were associated with notable pathological conditions, such as spontaneous hyperglycaemia in animals with hypertrophic islets and fibrosis or atrophy of the pancreas following duct ligation. Although these techniques provided foundational insights, their limited scalability and the pathological states associated with them highlighted the need for more advanced methods to reliably isolate intact islets.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"26 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434936","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

Exercise exacerbates cardiac damage from high-fat, high-calorie feeding in mice

IF 31 1区医学

Nature Reviews Endocrinology Pub Date : 2025-01-29 DOI: 10.1038/s41574-025-01087-y

Olivia Tysoe

引用次数: 0

The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease 1型和2型糖尿病对慢性肾病患者骨骼健康的影响

IF 40.5 1区医学

Nature Reviews Endocrinology Pub Date : 2025-01-16 DOI: 10.1038/s41574-024-01083-8

Jasna Aleksova, Peter Ebeling, Grahame Elder

{"title":"The effects of type 1 and type 2 diabetes mellitus on bone health in chronic kidney disease","authors":"Jasna Aleksova, Peter Ebeling, Grahame Elder","doi":"10.1038/s41574-024-01083-8","DOIUrl":"https://doi.org/10.1038/s41574-024-01083-8","url":null,"abstract":"Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.","PeriodicalId":18916,"journal":{"name":"Nature Reviews Endocrinology","volume":"53 1","pages":""},"PeriodicalIF":40.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986015","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

Exploring the functions of the myokine feimin 探索肌动蛋白 feimin 的功能

IF 31 1区医学

Nature Reviews Endocrinology Pub Date : 2025-01-15 DOI: 10.1038/s41574-025-01086-z

Claire Greenhill

引用次数: 0