American journal of physiology. Endocrinology and metabolism最新文献

{"title":"Correction for Yano et al., volume 318, 2020, p. E791-E805.","authors":"","doi":"10.1152/ajpendo.00219.2019_COR","DOIUrl":"https://doi.org/10.1152/ajpendo.00219.2019_COR","url":null,"abstract":"","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":"330 6","pages":"E811-E812"},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142381","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":"Exercise ameliorates adipose tissue insulin resistance by activating the lactate/GPR81 signaling pathway in DIO-IR mice.","authors":"Yihsuan Lin, Ge Song, Yue Chen, Chunyu Liang, Zhen Ni, Lijing Gong, Yi Yan","doi":"10.1152/ajpendo.00321.2025","DOIUrl":"10.1152/ajpendo.00321.2025","url":null,"abstract":"<p><p>Growing evidence indicates that both exogenous lactate administration and physical exercise improve insulin resistance (IR). This study investigates, from a novel perspective, whether exercise-induced lactate serves as a signaling molecule to ameliorate adipose tissue IR and explores the underlying mechanisms. Using diet-induced obese and insulin-resistant (DIO-IR) mice subjected to high-lactate exercise training, insulin-resistant 3T3-L1 (IR-3T3-L1) adipocytes treated with lactate, and a G protein-coupled receptor 81 (GPR81)-overexpressing cell line, we demonstrate three key findings: first, high-lactate exercise training markedly alleviated adipose tissue and systemic IR in DIO-IR mice. Second, acute high-lactate exercise mirrored the effects of l-lactate injection by elevating circulating and epididymal white adipose tissue (eWAT) lactate concentrations, concomitantly upregulating GPR81 and glucose uptake signaling expression while modulating adipokine secretion. Mechanistically, lactate/GPR81 signaling potentiated glucose uptake in IR-3T3-L1 adipocytes via the insulin receptor substrate 1 (IRS1)-AKT-glucose transporter 4 (GLUT4) pathway. Collectively, these results demonstrate that exercise-induced lactate enhances glucose uptake signaling and rebalances adipokine secretion. It may act as a signaling molecule that upregulates the specific receptor GPR81, thereby alleviating adipose tissue and systemic insulin resistance in DIO-IR mice. Our findings uncover a previously unrecognized link between exercise metabolism and adipose tissue homeostasis, highlighting lactate as a potential therapeutic target for IR-related metabolic disorders.<b>NEW & NOTEWORTHY</b> Exercise-induced lactate as a critical signaling molecule that ameliorates insulin resistance in obesity. Lactate enhances adipose tissue glucose uptake and rebalances adipokine secretion by upregulating the receptor G protein-coupled receptor 81 (GPR81). The findings establish lactate as an essential exercise metabolite with therapeutic potential for metabolic disorders.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E759-E773"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697066","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":"A role for vagal activity in preventing the suppression of glucagon secretion by GLP-1 during hypoglycemia.","authors":"Carolina B Lobato, Amalie B E Nielsen, Jens J Holst","doi":"10.1152/ajpendo.00236.2025","DOIUrl":"10.1152/ajpendo.00236.2025","url":null,"abstract":"<p><p>Glucagon-like peptide 1 (GLP-1) is generally safe against hypoglycemia, although it stimulates insulin and inhibits glucagon secretion. One explanation is that glucagon secretion is not inhibited by GLP-1 during hypoglycemia. We aimed at understanding the lack of suppression of glucagon secretion by GLP-1 by exploring the paracrine and neural regulation of pancreatic hormone secretion during hypoglycemia. Isolated rat pancreas (A) and an organ block comprising pancreas and stomach (B) were perfused. We performed <i>1</i>) dose-response studies with GLP-1 (7-36) at hypoglycemia; <i>2</i>) studies with GLP-1 (7-36) with and without blockage of somatostatin (SST) activity (with SST receptor antagonists); <i>3</i>) and <i>4</i>) dose-response experiments with acetylcholine at euglycemia and studies under hypoglycemia; and <i>5</i>) finally, we studied the role of cholinergic signaling for modulation of GLP-1 activity under hypoglycemia. We measured glucagon, SST, and insulin levels. The secretion of SST was dependent on surgical preparation (A or B, <i>P</i> = 0.0006) and on cholinergic stimulation (<i>P</i> < 0.0001), rather than on glucose levels (<i>P</i> > 0.05). The infusion of SSTR antagonists in the isolated perfused rat pancreas blocked the paracrine effects of SST (<i>P</i> = 0.0041) and stimulated glucagon secretion (<i>P</i> = 0.0023). Cholinergic activity stimulated glucagon secretion during hypoglycemia through suppression of SST secretion. Cholinergic signaling delivered through the gastric intramural autonomic ganglia and/or vagus nerve efferents to the pancreas appears to be crucial for preventing GLP-1-induced inhibition of glucagon secretion during hypoglycemia.<b>NEW & NOTEWORTHY</b> Autonomic signaling suppresses somatostatin secretion, crucial for paracrine stimulation of glucagon secretion. SST mediates GLP-1-induced inhibition of glucagon secretion, but autonomic signaling may interfere with this mechanism. Activation of cholinergic pathways in a preparation with prepancreatic parasympathetic structures suppresses SST secretion in response to GLP-1 and potentiates glucagon secretion during hypoglycemia. These findings support the clinical importance of autonomic signaling in regulating pancreatic hormone secretion and hypoglycemia risk in some patients on GLP-1 receptor agonists.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E737-E746"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669864","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":"Sex differences in exogenous glucose oxidation are attenuated by obesity: insights from a [U-¹³C₆]glucose home breath test.","authors":"Stephanie Estafanos, Daniel West, Anessa Koussiouris, Daniel R Moore, Jenna B Gillen","doi":"10.1152/ajpendo.00576.2025","DOIUrl":"10.1152/ajpendo.00576.2025","url":null,"abstract":"<p><p>Biological sex influences whole body glucose metabolism, with females generally displaying greater insulin sensitivity than males, yet paradoxically similar or poorer glucose tolerance when assessed with oral glucose tolerance tests (OGTTs). This discrepancy suggests that plasma glucose concentrations alone may not capture sex-specific differences in postprandial glucose metabolism. Measuring exogenous glucose oxidation during a [U-¹³C₆]glucose-enriched OGTT may offer a noninvasive approach to detect such differences, but this method has not yet been applied to examine sex differences. Forty adults (18-65 yr; <i>n</i> = 20/sex) classified as normal-weight (NW; <i>n</i> = 10/sex) or obese (OB; <i>n</i> = 10/sex) based on body mass index completed a virtually monitored metabolic trial. After a 10-h overnight fast, participants ingested a 75-g glucose beverage enriched with 75-mg (0.1%) [U-¹³C₆]d-glucose. Capillary glucose concentration, salivary insulin, and exogenous glucose oxidation were measured fasted and across the 3-h postprandial period. Compared with NW, participants with OB had higher 3-h mean blood glucose (<i>P</i> < 0.001) and salivary insulin (<i>P</i> < 0.001) concentrations, with no differences between sexes (all <i>P</i> > 0.05). A sex × obesity interaction was observed for exogenous glucose oxidation, such that it was higher in females than males in NW (69.1 ± 5.4 vs. 48.2 ± 7.5; <i>P</i> < 0.0001) but not in OB (40.9 ± 8.4 vs. 36.0 ± 9.3 mg/kg/h; <i>P</i> = 0.53). OB participants also exhibited lower overall exogenous glucose oxidation compared with NW (38.4 ± 8.8 vs. 58.7 ± 6.4 mg/kg/h; <i>P</i> < 0.001). These findings suggest that despite no sex differences in glucose or insulin responses during the OGTT, females exhibit higher exogenous glucose oxidation than males, but this elevated metabolic response is attenuated in obesity.<b>NEW & NOTEWORTHY</b> Using a [U-¹³C₆]glucose breath test during a 3-h OGTT, we show that normal-weight females oxidize a greater proportion of ingested glucose than males despite similar blood glucose and insulin responses. This sex difference is attenuated in obesity, which reduces overall glucose oxidation. These findings reveal sex-specific regulation of postprandial glucose metabolism not captured by conventional OGTT metrics and highlight breath testing as a sensitive, noninvasive approach for assessing glucose metabolism outside the laboratory.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E684-E693"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147607664","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":"Evidence for a role of calcium and vitamin D in the regulation of manganese homeostasis and in the prevention or management of manganese-induced disease.","authors":"Hope Lee, Sarah Marie Gerges, Simran Gill, Amro Tambal, Harneet Kaur Bahia, Mohamed Aburadi, Shivani Grover, Somshuvra Mukhopadhyay, Cathleen L Doherty, Sean Stratton, Sylvia Christakos","doi":"10.1152/ajpendo.00511.2025","DOIUrl":"10.1152/ajpendo.00511.2025","url":null,"abstract":"<p><p>SLC30A10 mediates manganese (Mn) efflux in both the intestine and liver, protecting against Mn toxicity. In previous studies, we found that <i>Slc30a10</i> is one of the genes most induced by 1,25(OH)₂D₃ in mouse intestine and human enteroids. In addition, in <i>Slc30a10</i> knockout mice, we noted a significant decrease in <i>Trpv6</i>, a vitamin D target gene involved in intestinal calcium transport, indicating a link between Mn efflux transport in the intestine, calcium, and the vitamin D endocrine system. In this study, we examined the effect of varying levels of Mn in 3-wk-old male and female mice fed diets either low, adequate, or high in calcium for 4 wk. Mn levels were markedly elevated in the mice fed the low calcium diets (0.02%, 0.1%) in tissues and blood. Under low calcium conditions, serum 1,25(OH)₂D₃ and intestinal <i>Slc30a10</i> were induced as possible compensatory mechanisms to manage Mn toxicity. However, when older mice were similarly fed a high Mn low calcium diet for 4 wk, there was a decrease in serum 1,25(OH)₂D₃, in renal <i>Cyp27b1</i> and either no effect or a decreased Mn response to low calcium in tissues and blood. Our findings indicate that low dietary calcium may contribute to the pathogenesis of Mn-induced toxicity, that the interactions between Mn and calcium are mediated in part by 1,25(OH)₂D₃ and that there is a protective mechanism of control of Mn homeostasis by vitamin D and calcium with potential therapeutic relevance for the prevention or management of Mn-induced disease.<b>NEW & NOTEWORTHY</b> This study demonstrates that low calcium levels in growing mice markedly elevate Mn in blood and other tissues thus contributing to the pathogenesis of Mn-induced toxicity, that interaction between Mn and calcium are mediated in part by 1,25(OH)₂D₃ and that there is a protective mechanism of control of Mn homeostasis by vitamin D and calcium with potential therapeutic relevance for prevention or management of Mn induced diseases.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E728-E736"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618189","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":"Acute metabolic and molecular responses to sprint interval versus moderate-intensity continuous exercise in healthy young men.","authors":"Enda Murphy, Claire Laurens, Laurie Frances, Marie-Adeline Marquès, François Crampes, Isabelle de Glisezinski, Javier Monedero, Helena Kenny, Noel McCaffrey, Francis M Finucane, Cedric Moro, Donal O'Gorman","doi":"10.1152/ajpendo.00548.2025","DOIUrl":"10.1152/ajpendo.00548.2025","url":null,"abstract":"<p><p>Exercise intensity is a key determinant of the physiological responses in skeletal muscle that lead to improvements in human health. Whether a bout of brief supramaximal acute exercise has similar effects on muscle physiology and metabolic health to a longer bout of continuous acute exercise remains unclear. In a randomized cross-over design, 12 healthy young recreationally active men completed single acute bouts of either sprint interval exercise (SIE; seven repeated 30 s maximal sprints at 130% over 35 min) or moderate-intensity continuous exercise (MICE; cycling at 65% effort over 60 min), or a nonexercise control (CON) session, on separate days. Acute changes in skeletal muscle insulin sensitivity were measured with a hyperinsulinemic euglycemic clamp. Muscle biopsies were performed to quantify changes in muscle glycogen content and insulin signaling proteins. Despite a sixfold lower total mechanical work in SIE versus MICE, SIE elicited greater and more prolonged increases in whole body insulin sensitivity, with greater preclamp muscle glycogen depletion and glycogen repletion during the clamp. We found reduced glycogen synthase and glycogen synthase kinase-3β phosphorylation, with no differences in Akt Thr308/Ser473 phosphorylation. A single session of sprint interval exercise elicits more pronounced effects on several measures of skeletal muscle insulin sensitivity than a single bout of moderate-intensity continuous exercise, despite substantially lower mechanical work and time commitment. These findings indicate that exercise intensity is a key mediator of acute skeletal muscle metabolic adaptations to exercise and suggest that sprint interval exercise represents a highly time-efficient stimulus for improving skeletal muscle insulin responsiveness.<b>NEW & NOTEWORTHY</b> This study shows that a single bout of sprint interval exercise produces greater acute improvements in whole body and skeletal muscle insulin sensitivity than a much longer session of moderate-intensity continuous exercise, despite requiring far less total work and time. The findings highlight exercise intensity, not duration, as a key driver of rapid metabolic adaptations and identify sprint interval exercise as a highly time-efficient strategy for enhancing insulin sensitivity.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E562-E571"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455259","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":"Maternal exercise during lactation remodels obesity-associated mammary metabolism and milk fatty acids, enhancing offspring lipid oxidation.","authors":"Gertrude Kyere-Davies, Kaitlyn B Hill, Gregory P Mullen, Rohan R Varshney, Snehasis Das, Alexandrea Martinez, Jacob W Farriester, Michael Kinter, Cassie M Mitchell, Kevin R Short, Elvira M Isganaitis, David A Fields, Michael C Rudolph","doi":"10.1152/ajpendo.00399.2025","DOIUrl":"10.1152/ajpendo.00399.2025","url":null,"abstract":"<p><p>Maternal obesity alters breast milk composition in ways that may predispose infants to excess adiposity. Although maternal exercise during lactation has been associated with favorable shifts in milk metabolites in humans, the mechanisms by which exercise remodels the mammary gland and milk lipid profile to influence offspring metabolism remain unclear. We developed a mouse model incorporating daily moderate treadmill exercise only during lactation, using lean (LN) and diet-induced obese (OB) dams, and leveraged indirect calorimetry, stable isotope tracer respirometry, and mammary epithelial cell (MEC) proteomics assays. Maternal obesity broadly remodeled the MEC proteome, decreasing enzymes of de novo fatty acid synthesis and altering lipid transport and oxidative pathways. These molecular adaptations in OB dams corresponded to higher milk triglyceride content and shifts in fatty acid composition, including suppressed medium-chain fatty acids (MCFAs). The exercise (EX) intervention during lactation reset MEC protein networks, enhancing protein translation and vesicle transport pathways, whereas decreasing fatty acid desaturation, relative to the sedentary (SED) group. In OB dams, the exercise intervention increased milk MCFA levels and partially corrected the proinflammatory omega-6 fatty acid bias. Offspring suckling OB-EX dams exhibited enhanced in vivo fatty acid oxidation, partially rescuing obesity-associated impairments in metabolic fuel preference. Together, maternal exercise during lactation remodels mammary metabolism and milk fatty acid composition in obese dams, which in turn, enhances postnatal lipid oxidation. These findings highlight lactation as a modifiable window, wherein maternal activity influences milk composition and early life metabolism.<b>NEW & NOTEWORTHY</b> Maternal obesity alters milk fatty acid composition, with consequences for postnatal metabolism. Maternal exercise during lactation in obese dams remodeled the mammary epithelial cell proteome, increasing medium-chain fatty acids in milk and enhancing offspring lipid oxidation.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E541-E561"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497329","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":"Testosterone administration partially modulates gut microbiota responses to severe energy deficit.","authors":"Alex E Mohr, Claire E Berryman, Melissa N Harris, Alexander B Lawrence, Nabarun Chakraborty, Ross Campbell, George I Dimitrov, Aarti Gautam, Rasha Hammamieh, Harris R Lieberman, Jennifer C Rood, Stefan M Pasiakos, J Philip Karl","doi":"10.1152/ajpendo.00291.2025","DOIUrl":"10.1152/ajpendo.00291.2025","url":null,"abstract":"<p><p>Severe diet- and exercise-induced energy deficit (SED) suppresses androgen production in healthy men, altering metabolism and driving muscle loss. The gut microbiota modulates host metabolism, yet the community's response to SED and any role of androgen hormones are unclear. Herein, healthy, physically active men were randomized to receive 200 mg/wk testosterone enanthate (<i>n</i> = 24) or placebo (<i>n</i> = 26) during a 28-day residential intervention that restricted energy intake and increased energy expenditure inducing a ∼2,000 kcal/day SED. Multiomic analyses revealed altered gut microbiota composition, reduced fecal short-chain fatty acids (SCFA), and shifts in bacterial metabolic pathways toward lipid utilization and mucin degradation during SED, suggesting adverse effects of SED on gut microbiota metabolic functions. Testosterone administration preserved certain SCFA-producing taxa and bioenergetic pathways without fully counteracting the effects of SED indicating a limited but potentially important interplay between androgen status and the gut microbiota under conditions of SED.<b>NEW & NOTEWORTHY</b> This study is the first to demonstrate that testosterone administration partially preserves gut microbiota composition and metabolic function during severe energy deficit in healthy men. Using a multiomic approach, we show that testosterone modulates short-chain fatty acid-producing taxa and microbial pathways linked to host energy metabolism. These findings reveal a novel role for androgens in shaping host-microbiome interactions during catabolic stress and may inform strategies to maintain metabolic resilience.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E606-E626"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13256601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147502649","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":"Impact of infusing the cholesterol precursor mevalonate on the hypocholesterolemia of sepsis and its potential consequences: a paradoxical response.","authors":"Lauren De Bruyn, Sarah Derde, Fien Van Beek, Inge Derese, Lies Pauwels, Sarah Vander Perre, Greet Van den Berghe, Lies Langouche","doi":"10.1152/ajpendo.00514.2025","DOIUrl":"10.1152/ajpendo.00514.2025","url":null,"abstract":"<p><p>Hypocholesterolemia hallmarks sepsis, though its pathophysiology and tissue-specific consequences are unclear. As low circulating cholesterol may reflect impaired endogenous cholesterol synthesis, we hypothesized that infusion of the cholesterol precursor mevalonate can reverse sepsis-induced hypocholesterolemia, whereby beneficially affecting adrenal and muscle integrity. In a catheterized mouse model of cecal ligation and puncture-induced sepsis (male 24-wk-old C57BL/6J mice), septic mice received either 5-day mevalonate infusion (78 mg/day) or placebo versus healthy controls (<i>n</i> = 50). Plasma high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, corticosterone, total bile acids, adrenocortical lipids, myofiber cholesterol, and muscle force were quantified. Expression markers of cholesterol homeostasis and structural integrity were investigated in adrenal, muscle and liver tissue. Liver mevalonate metabolites were quantified with liquid chromatography-mass spectrometry (LC-MS). Next, a secondary analysis on a prospective observational human study on the time course of adrenal function in the intensive care unit was performed to assess the association between plasma cholesterol and cortisol (<i>n</i> = 47). Also, plasma mevalonate was quantified with LC-MS. In septic mice, 5-day mevalonate infusion worsened HDL and LDL hypocholesterolemia versus placebo (<i>P</i> < 0.05). Decreased hepatic cholesterol synthesis expression markers, apolipoproteins, and hepatic cholesterol concentrations were observed in mevalonate-infused septic mice versus placebo (<i>P</i> < 0.05). No additional effect on plasma corticosterone, bile acids, myofiber cholesterol, and loss of muscle force and adrenocortical lipid depletion was observed. In prolonged sepsis patients, plasma mevalonate was increased, whereas plasma HDL- and LDL-cholesterol were low (<i>P</i> < 0.05) but did not correlate with plasma cortisol. To conclude, mevalonate infusion worsened sepsis-induced hypocholesterolemia, possibly due to increased feedback on hepatic cholesterol synthesis, without aggravating the adrenal or muscle sepsis phenotype.<b>NEW & NOTEWORTHY</b> Prolonged infusion with the cholesterol precursor, mevalonate, worsened hypocholesterolemia in a mouse model of sepsis-induced critical illness, likely due to increased feedback on hepatic cholesterol synthesis. Loss of muscle force and mass was not further affected, nor did mevalonate affect adrenal gland steroidogenic markers and the loss of adrenocortical lipids. In prolonged sepsis patients, sustained HDL and LDL hypocholesterolemia was observed in the face of high plasma mevalonate concentrations, but did not correlate with plasma cortisol.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E694-E706"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615502","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":"Pretransplant aerobic exercise improves glycemic outcomes after marginal islet mass transplantation in rats.","authors":"Jordan M Wong, Seyed Amirhossein Tabatabaei Dakhili, Purushothaman Kuppan, Joy Paramor, Nerea Cuesta-Gomez, John R Ussher, Caroline Richard, C W James Melling, Corbin Nitz, Jane E Yardley, Andrew R Pepper","doi":"10.1152/ajpendo.00007.2025","DOIUrl":"10.1152/ajpendo.00007.2025","url":null,"abstract":"<p><p>Pancreatic islet transplantation (ITx) improves glycemic management and prevents severe hypoglycemia in select individuals with type 1 diabetes (T1D). However, insulin independence cannot be guaranteed due to transplant and recipient-specific factors, limiting broad application. Exercise improves insulin sensitivity, reduces chronic inflammation, increases insulin-independent glucose uptake, and can decrease the risk of surgery-related complications. Therefore, we examined the utility of pretransplant exercise in the context of ITx on metabolic and immune outcomes. Streptozotocin (STZ)-induced diabetic rats performed voluntary, 1-h wheel-running exercise in an overnight-fasted state on three nonconsecutive days weekly for 4 wk preceding transplantation. Exercised (RUN, <i>n</i> = 7) and sedentary (SIT, <i>n</i> = 6) rats underwent marginal syngeneic ITx. Graft efficacy was compared with nonfasted blood glucose readings and a 4-wk intraperitoneal glucose challenge. At 4 wk posttransplant, 100% (7/7) of RUN rats became euglycemic compared with 66% (4/6) in the SIT condition (<i>P</i> < 0.05). RUN recipients demonstrated superior nonfasting blood glucose and weight gain (<i>P</i> < 0.05) and comparable glucose tolerance to naïve rats, whereas SIT rats had inferior clearance (<i>P</i> < 0.05), despite comparable proportions of insulin and glucagon graft-positive cells. Reduction in RUN adipose tissue macrophages suggests lower inflammation levels alongside greater insulin sensitivity based on the quantitative insulin-sensitivity check index (QUICKI) (<i>P</i> < 0.01). Moreover, the soleus muscle of RUN recipients had lower levels of pyruvate dehydrogenase phosphorylation at serine 232 (<i>P</i> < 0.05), and increased levels of phosphorylated glycogen synthase kinase (<i>P</i> < 0.05), suggestive of increased carbohydrate oxidation and insulin signaling, respectively. Altogether, we demonstrate that pretransplant exercise may enhance glycemic outcomes in ITx due to lower inflammation levels and increased carbohydrate oxidation.<b>NEW & NOTEWORTHY</b> To our knowledge, there have yet to be any formal investigations into the role of prehabilitation exercise in ITx. Our exciting preliminary work highlights a noninvasive and feasible approach that may improve the outcomes of this functionally curative procedure. Our findings presented support additional investigation into prehabilitation in ITx, which can encompass a wide array of exercise regimens.</p>","PeriodicalId":7594,"journal":{"name":"American journal of physiology. Endocrinology and metabolism","volume":" ","pages":"E715-E727"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147643596","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}