American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Glucagon receptor deficiency is associated with glucocorticoid receptor activation and proteolytic remodeling in gastrocnemius of male mice.","authors":"Xuanxuan Bai, Tongyu Zhang, Chao Zhang, Mingyu Li","doi":"10.1152/ajpendo.00076.2026","DOIUrl":"10.1152/ajpendo.00076.2026","url":null,"abstract":"<p><p>Glucagon signaling through the glucagon receptor (GCGR) plays a central role in systemic metabolic regulation. However, its role in skeletal muscle protein homeostasis remains poorly understood. In this study, we demonstrated that skeletal muscle from male GCGR-deficient mice exhibited preferential gastrocnemius atrophy accompanied by elevated intramuscular free amino acid levels and hyperaminoacidemia. Transcriptomic and biochemical analyses revealed activation of glucocorticoid receptor (GR) signaling together with induction of proteolytic pathways, as reflected by increased tripartite motif containing 63 (TRIM63) and F-box protein 32 (FBXO32) levels, elevated light chain 3B-II/I (LC3B-II/I) ratio, and reduced p62 levels. Notably, GCGR deficiency was associated with increased corticosterone and subsequent GR activation. In cultured myotubes, serum from male <i>Gcgr</i>^-/- mice induced GR activation, enhanced proteolysis, and increased intracellular free amino acid levels, all of which were attenuated by GR antagonism. Consistently, dexamethasone stimulation increased net amino acid accumulation in the culture medium. Moreover, the GR activation-resulted gastrocnemius atrophy was alleviated by glucagon-like peptide-1 receptor (GLP-1R) antagonism. These findings link GCGR deficiency to GR activation, gastrocnemius proteolysis, hyperaminoacidemia, and elevated GLP-1 signaling, suggesting a role for skeletal muscle in systemic amino acid homeostasis under impaired GCGR signaling.<b>NEW & NOTEWORTHY</b> Glucagon receptor signaling is classically viewed as acting primarily in the liver to regulate amino acid homeostasis. Here, we show that loss of GCGR signaling in male mice is associated with preferential gastrocnemius atrophy, accompanied by enhanced glucocorticoid receptor activation and increased proteolytic markers in gastrocnemius, which can be rescued by GLP-1R antagonism. These alterations occur together with intramuscular free amino acid accumulation and hyperaminoacidemia, suggesting that skeletal muscle is affected by disrupted GCGR signaling.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E425-E438"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of intestinal propionate metabolism on systemic metabolic homeostasis.","authors":"Jasmine Encarnacion, Michael J Wolfgang","doi":"10.1152/ajpendo.00168.2026","DOIUrl":"10.1152/ajpendo.00168.2026","url":null,"abstract":"<p><p>Propionate is an abundant short-chain fatty acid largely derived from gut microbiota in mammals. Propionate metabolism is essential to maintain systemic homeostasis, and inborn errors of essential metabolic enzymes in this pathway cause severe illness. The juxtaposition of high concentrations of propionate with the intestinal epithelium suggests a need for propionate catabolism. To understand the requirement of propionate metabolism in intestinal epithelium, we generated mice with a conditional knockout of propionyl-CoA carboxylase A (Pcca) specifically in the intestine (<i>Pcca</i>^Vil-Cre). Male and female <i>Pcca</i>^Vil-Cre mice were born and weaned at the expected Mendelian ratio and gained weight normally on chow and high-fat diets. Liver metabolomics of <i>Pcca</i>^Vil-Cre mice suggest that propionate metabolism affects the gut-liver axis. However, the loss of Pcca in the intestine did not affect the colonic transcriptome. These data suggest that intestinal propionate metabolism is largely dispensable, and that hepatic capture and metabolism of propionate dominate systemic physiology.<b>NEW & NOTEWORTHY</b> Propionate generated by the microbiome is extremely high in the lumen of the gut. To determine the requirement of propionate metabolism in the gut, we generated and characterized mice with an intestine-specific knockout of propionyl-CoA carboxcylase alpha (PCCA), the first step in propionyl-CoA metabolism. Overall, mice that are unable to use propionate in the intestine are relatively normal with alterations in the gut-liver axis.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E414-E424"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of ¹³C MRS demonstrates carbohydrate feeding spares muscle but not liver glycogen utilization during high-intensity interval exercise.","authors":"Sophie C Hannon, Libby Henthorn, Jay Vadher, Catharine Montgomery, George F Pavis, Francis B Stephens, Benjamin T Wall, Nathan Hodson, James P Morton, Aneurin J Kennerley, Mark A Hearris","doi":"10.1152/ajpendo.00139.2026","DOIUrl":"10.1152/ajpendo.00139.2026","url":null,"abstract":"<p><p>We examined liver and muscle glycogen utilization during high-intensity interval cycling, and the impact of carbohydrate (CHO) feeding, using noninvasive ¹³C magnetic resonance spectroscopy (MRS). Following 24 h of standardized dietary intake, nine male cyclists completed 8 × 5-min intervals (1-min recovery), ingesting either placebo (PLA), 60 g maltodextrin (CHO), or 60 g maltodextrin plus caffeine, taurine, l-theanine, l-citrulline, and citicoline (CHO⁺) in a randomized crossover design. ¹³C MRS and ¹H imaging were performed pre- and postexercise to determine liver and muscle glycogen and liver volume, respectively. Liver glycogen utilization was not significantly different between trials (<i>P</i> = 0.101) despite lower postexercise plasma glucagon concentrations in CHO and CHO⁺ (<i>P</i> = 0.001). In contrast, muscle glycogen utilization was significantly lower (∼40%) with CHO feeding compared with PLA (<i>P</i> = 0.006), yet this sparing effect was not evident with CHO⁺ (<i>P</i> = 0.073) in accordance with a higher mean power output during the late intervals (+2.8%, <i>P</i> = 0.046). Plasma glucose was comparable between trials (<i>P</i> = 0.175), whereas plasma lactate was higher in CHO⁺ versus CHO (<i>P</i> = 0.003), alongside lower blood bicarbonate (<i>P</i> = 0.005), base excess (<i>P</i> < 0.001), and total CO₂ (<i>P</i> = 0.004). These findings demonstrate preferential use of skeletal muscle glycogen during high-intensity interval training (HIIT), which is attenuated under conditions of CHO feeding. This sparing effect is, however, not evident with the coingestion of a caffeine-containing multi-ingredient blend, potentially due to an increased capacity to sustain higher power outputs resulting in greater glycogen utilization.<b>NEW & NOTEWORTHY</b> Using ¹³C MRS, we provide data demonstrating preferential use of skeletal muscle glycogen during HIIT. Furthermore, data show muscle glycogen utilization is attenuated with CHO feeding, yet sparing is not evident when coingesting a caffeine-containing formulation, potentially reflecting increased capacity to perform more total work rather than a direct metabolic effect of caffeine. In contrast, liver glycogen utilization was not significantly different with CHO feeding despite a modest reduction of ∼5 g versus placebo.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E320-E334"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap: multi-omic insights into exercise responses in postmenopausal women.","authors":"Rushali Kullachanda Aiyanna, Sisi Wang, Robin Grolaux, Elizabeth Reisman, Bernadette Jones-Freeman, Nir Eynon","doi":"10.1152/ajpendo.00172.2026","DOIUrl":"10.1152/ajpendo.00172.2026","url":null,"abstract":"<p><p>Postmenopausal women represent the fastest-growing demographic at risk of sarcopenia and cardiometabolic disease, yet exercise biology research remains disproportionately derived from male or hormone-replete phenotypes. Menopause constitutes a chronic endocrine perturbation characterized by sustained reductions in estrogen and progesterone, and altered androgen balance, superimposed on the acute and chronic perturbations induced by exercise. This hormonal shift modifies substrate metabolism, inflammation, redox balance, and recovery capacity, factors that shape molecular responses to exercise across tissues and time. Here, we synthesize current evidence on exercise responses in postmenopausal females across genomics, epigenomics, transcriptomics, proteomics, and metabolomics/lipidomics. Across omics layers, direct data in postmenopausal cohorts remain limited, with frequent underreporting of menopausal status, hormone therapy exposure, circulating hormone concentrations, medication use, and biosampling timing relative to exercise and hormone dosing. We outline a menopause-aware framework for exercise-omics that prioritizes endocrine stratification, repeated sampling across exercise and recovery, and integrative multi-omics approaches linking molecular responses to functional outcomes. We also outline minimum reporting standards to improve reproducibility, inclusivity, and translational relevance. Advancing menopause-aware exercise-omics will be essential for developing precision exercise strategies that improve health span and functional independence in later life.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E272-E288"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell dissection of cholesterol metabolism reveals cell-type-specific genes and hypercholesterolemia-associated remodeling.","authors":"Jian Chu, Jing Zhuang, Shuwen Han, Yujiu Liang, Jing Mao, Zian Zhang, Caiyun Chu, Xi Yang","doi":"10.1152/ajpendo.00090.2026","DOIUrl":"10.1152/ajpendo.00090.2026","url":null,"abstract":"<p><p>This study was aimed at systematically characterizing cell-type-specific cholesterol metabolism in human blood samples and investigating the impact of hypercholesterolemia on the composition and gene expression of immune and stromal populations. Single-cell RNA sequencing (scRNA-seq) data from 31 human blood samples, encompassing 472,204 high-quality circulating cells, were analyzed. Pathway activities were assessed via gene set variation analysis (GSVA), and cell-type-specific markers were identified using differential expression analysis. Clinical cholesterol levels were used to stratify samples for comparative analysis of cell abundance and transcriptional changes. Monocytes and macrophages were found to exhibit heightened activity in cholesterol transport and dynamic response pathways. Five monocyte-enriched cholesterol metabolism genes (colony-stimulating factor 3 receptor, formyl peptide receptor 1, myeloid cell nuclear differentiation antigen, macrophage-expressed gene 1, and versican) were identified. Hypercholesterolemia was associated with increased abundance of macrophages, T cells, and natural killer cells, as well as decreased B cells and monocytes. Significant upregulation of proinflammatory genes such as VCAM1 in high-cholesterol conditions was revealed by differential gene expression analysis. Our study provided a comprehensive cell-type-specific atlas of cholesterol metabolism in human blood cells, highlighting metabolic heterogeneity and hypercholesterolemia-induced immune remodeling in the circulation. This resource offered novel insights into cholesterol-mediated immunomodulation.<b>NEW & NOTEWORTHY</b> Monocytes and macrophages display elevated activity in cholesterol transport and dynamic response pathways. Five monocyte-enriched genes (CSF3R, FPR1, MNDA, MPEG1, VCAN) are implicated in cholesterol metabolism regulation. Hypercholesterolemia reshapes circulating immune cell composition and upregulates proinflammatory genes (e.g., VCAM1), mediating immunomodulatory effects.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E289-E299"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of β-Klotho in FGF signaling: from molecular insights to therapeutic innovations.","authors":"Fang Yan, Chen Yang, ShiYuan Huang, Li Yuan, Yi Qiu, Tao Liu, Xi Peng, Yang Yang","doi":"10.1152/ajpendo.00042.2026","DOIUrl":"10.1152/ajpendo.00042.2026","url":null,"abstract":"<p><p>β-Klotho (KLB) is a transmembrane protein expressed in the liver, pancreas, hypothalamus, and adipose tissue, where it acts as an essential coreceptor for fibroblast growth factor 19 and 21 (FGF19 and FGF21). By facilitating their binding to fibroblast growth factor receptors (FGFRs), KLB helps form critical endocrine axes that regulate a wide range of physiological processes and are implicated in various diseases. This review summarizes current knowledge of KLB, focusing on its structural and functional features as well as the physiological roles of the FGF19-KLB and FGF21-KLB axes. A comprehensive analysis of the literature confirms that KLB is indispensable for high-affinity signaling of FGF19 and FGF21. The FGF19-KLB axis primarily controls bile acid synthesis, glucose metabolism, and energy expenditure, thereby modulating glucose/lipid homeostasis, energy balance, and insulin sensitivity. Dysregulation of these axes is linked not only to metabolic disorders such as diabetes, metabolic dysfunction-associated steatotic liver disease/metabolic dysfunction-associated steatohepatitis (MASLD/MASH), and obesity but also to certain malignancies and neurological disturbances, underscoring their broad role in disease. Growing evidence highlights the therapeutic potential of targeting these pathways, supporting their value as drug targets for novel treatments, especially in metabolic disease. This review consolidates understanding of the central roles played by KLB-mediated signaling in metabolic homeostasis and disease, examines its emerging relevance in cancer and neural regulation, and emphasizes the need to advance KLB biology to fully exploit its potential as a multifunctional therapeutic target.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E253-E271"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using thermal preference to understand mouse thermal biology.","authors":"Cuiying Xiao, Tamar C Demby, Naili Liu, Oksana Gavrilova, Marc L Reitman","doi":"10.1152/ajpendo.00506.2025","DOIUrl":"10.1152/ajpendo.00506.2025","url":null,"abstract":"<p><p>The ability to tightly regulate and maintain a warm core body temperature (T_b) is a defining characteristic of homeotherms. Moving to a thermally preferred place is an energetically efficient first-line thermoregulatory mechanism. We optimized a mouse binary thermal preference assay, selecting floor plate temperatures of 38°C versus 25°C for males and 39°C versus 30°C for females as having no baseline preference. Warm preference was increased in females, by fasting, and with age. Genetic manipulations that increased warm preference included ablation of uncoupling protein 1 (<i>Ucp1</i>) or of all four adenosine receptors (<i>Adora1</i>, <i>Adora2a</i>, <i>Adora2b</i>, <i>Adora3</i>). Ablation of estrogen receptor α (<i>Esr1</i>) reduced the preference for the warmer side in females but had no effect on preference in males. Mice treated with the β₃ adrenergic receptor agonist CL-316243 or the A3 adenosine receptor agonist MRS5698 sought the cooler surface. Thermal preference assays complement the measurement of T_b, providing information about whether a change in T_b reflects a new target or set point T_b caused by the intervention, or if the mouse is trying to maintain an unchanged T_b. Thermal preference can be more sensitive than baseline T_b for detecting changes in thermal physiology.<b>NEW & NOTEWORTHY</b> A thermal preference assay optimized for each sex demonstrated preference differences depending on physiologic state, genetic manipulation, and drug treatment. Thermal preference assays provide information that is complementary to measurement of core body temperature. Thermal preference can be more sensitive to perturbations than baseline body temperature and informs the understanding of how genetic, pharmacologic, and physiologic interventions alter thermoregulatory drive.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E312-E319"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13596097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148683094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Hydroxybutyrate: a renoprotective hormone in polycystic kidney disease.","authors":"Jacob A Torres, Elizabeth H Sharpe, Thomas Weimbs","doi":"10.1152/ajpendo.00067.2026","DOIUrl":"10.1152/ajpendo.00067.2026","url":null,"abstract":"<p><p>Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic form of chronic kidney disease characterized by highly variable rates of progression. This variability suggests that nutritional, lifestyle, and environmental factors may significantly influence disease course. Despite its prevalence, pharmacological treatment options for ADPKD remain very limited, underscoring the urgent need for safe and effective therapeutic strategies. Recent research has identified ADPKD as a metabolic disorder at the cellular level, marked by impaired mitochondrial function and a pathological reliance on glucose metabolism in affected cells. Ketogenic metabolic therapy (KMT) targets this metabolic vulnerability and has shown promising outcomes in both preclinical models and early clinical studies. KMT encompasses a range of interventions including ketogenic diets, intermittent fasting, time-restricted feeding, and supplementation with the ketone body β-hydroxybutyrate (BHB). Accumulating evidence suggests that BHB is the principal renoprotective mediator underlying the therapeutic benefits of KMT. Beyond serving as an alternative energy substrate, BHB exerts pleiotropic signaling effects that may synergistically contribute to reduced cyst proliferation, inflammation, oxidative stress, and fibrosis, while enhancing mitochondrial function. These attributes position BHB as a renoprotective signaling hormone. Importantly, chronic suppression of endogenous ketogenesis is common in modern societies because of dietary and lifestyle patterns and may deprive tissues of BHB's pleiotropic signaling functions. In this narrative review, we summarize the current understanding of KMT and BHB in the context of ADPKD and discuss their potential as safe, noninvasive, and disease-modifying interventions.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E300-E311"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics approaches reveal direct NF-κB p65 target genes in pancreatic islets during cytokine exposure and in type 1 diabetes.","authors":"Thomas M Martin, Susan J Burke, Heidi M Batdorf, Andrew M Lipchik, Pravalika Javvadi, Sujoy Ghosh, J Jason Collier","doi":"10.1152/ajpendo.00498.2025","DOIUrl":"10.1152/ajpendo.00498.2025","url":null,"abstract":"<p><p>Autoimmune diseases, including Type 1 diabetes (T1D), are often characterized by overactive inflammatory signaling pathways. The proinflammatory cytokine interleukin-1β (IL-1β) elicits global gene expression changes in islet β-cells which overlap with islets obtained from human donors with T1D. The direct transcriptional link between NF-κB subunit p65 and target genes involved with autoimmune events was investigated. We used a multiomics approach including bulk RNA-sequencing (RNA-Seq), single-cell RNA-sequencing (scRNA-Seq), and chromatin immunoprecipitation coupled to deep sequencing (ChIP-Seq), alongside molecular docking simulations, and transcriptional assays. Through the various experimental modalities, we identified early response genes driven by IL-1β that were differentially expressed in pancreatic islets from human T1D donors and also conserved across mouse, rat, and human tissues. ChIP-Seq revealed genes that are direct genomic targets of the NF-κB p65 transcription factor. Moreover, regions that gained RNA polymerase II binding following cellular exposure to IL-1β were identified, complementing the early response gene profile induced by β-cell exposure to IL-1β. Molecular docking simulations predicted that mutations reducing p65 transcriptional capacity do not alter DNA binding ability. These findings clearly show that IL-1β signaling in pancreatic β-cells directs p65 to specific genomic regions congruent with increased gene expression relevant to T1D in β-cell lines as well as mouse and human islets exposed to cytokines. Islets from human donors with T1D express genes identified as direct p65 targets using unbiased approaches, implicating heightened NF-κB activity as a critical component of autoimmune disease etiology.<b>NEW & NOTEWORTHY</b> Using multiple Seq-based approaches, this study identified genes expressed in human pancreatic tissue from donors with Type 1 diabetes that are regulated acutely by exposure to the cytokine interleukin-1beta. The NF-kB transcription factor p65 (RelA) was determined via ChIP-Seq to be a major control node regulating this immediate early response. These collective datasets are consistent with a paradigm of overactive NF-kB signaling as a critical component of autoimmunity in both rodents and humans.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E347-E362"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose curve morphology and peak time as biomarkers of metabolic health.","authors":"Zahra Fatahimeiabadi, Jehu Narh Apaflo, Sudip Bajpeyi","doi":"10.1152/ajpendo.00550.2025","DOIUrl":"10.1152/ajpendo.00550.2025","url":null,"abstract":"<p><p>The oral glucose tolerance test (OGTT) is widely used to assess glucose tolerance, but the conventional 2-h postprandial glucose value faces limited reliability. Alternative OGTT-derived indices, such as the shape of the glucose curve and the time to glucose peak, may offer additional insights into metabolic health. This study examined whether these indices could serve as biomarkers of metabolic risk. Normoglycemic adults [<i>n</i> = 85 (males: 40; females: 45); age: 26.9 ± 4.6 yr; body mass index: 23.1 ± 2.4 kg/m²] underwent a 3-h OGTT, with repeated measurements of blood glucose, insulin, and free fatty acids (FFAs). Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp. Energy expenditure (EE) and sleep respiratory quotient (RQ) were measured by metabolic chamber, and body composition by the EchoMRI-AH. Participants were classified by glucose curve morphology (monophasic vs. biphasic) and glucose peak time (early: ≤30 min vs. late: >30 min). Compared with the monophasic group, the biphasic group showed lower postprandial glucose (<i>P</i> < 0.05), with no differences in 3-h glucose area under the curve (AUC), insulin AUC, insulin sensitivity, FFA, EE, RQ, or body fat. In contrast, the early peak exhibited lower postprandial glucose, 3-h insulin AUC, 2-h FFA AUC, RQ, and body fat, with higher EE (<i>P</i> < 0.05) and a trend toward higher insulin sensitivity (<i>P</i> = 0.0592), compared with the late-peak group. Biphasic glucose curves and early glucose peak time indicate better glucose tolerance and insulin sensitivity. Compared with glucose curve morphology, glucose peak time demonstrated a stronger discriminative index of metabolic health and could serve as an additional biomarker of the OGTT for identifying potential diabetes risks.<b>NEW & NOTEWORTHY</b> Participants in biphasic groups showed better glucose tolerance than monophasic participants. Participants in early-peak groups showed better glycemic control and energy metabolism than late-peak participants. Glucose peak time demonstrates a stronger discriminative index of metabolic health than glucose curve morphology. Glucose peak time could serve as a useful biomarker of the OGTT for identifying potential diabetes risks.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E335-E346"},"PeriodicalIF":4.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13543240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}