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Hexokinase-2–glycolytic overload axis in brain disorders exacerbated by diabetes 糖尿病加重脑疾病的己糖激酶-2糖酵解超载轴
Trends in Endocrinology & Metabolism Pub Date : 2026-09-29 DOI: 10.1016/j.tem.2026.09.006
Muhanad Alhujaily,Naila Rabbani,Paul J. Thornalley
{"title":"Hexokinase-2–glycolytic overload axis in brain disorders exacerbated by diabetes","authors":"Muhanad Alhujaily,Naila Rabbani,Paul J. Thornalley","doi":"10.1016/j.tem.2026.09.006","DOIUrl":"https://doi.org/10.1016/j.tem.2026.09.006","url":null,"abstract":"Subjects with diabetes have an increased risk of dementia, Parkinson’s disease, and stroke. In the central nervous system, there is increased inflammation, blood–brain barrier permeability, amyloid-β and α-synuclein deposition, and decreased neuronal synaptogenesis and survival. The role of hexokinases in controlling glucose metabolism therein is often overlooked. We propose that hexokinase-2 dysfunction-driven glycolytic overload is critically involved. This increases glycolytic intermediates in astrocytes, microglial cells, microvessel endothelial cells, and pericytes, stimulating mitochondrial dysfunction, protein O-linked β-N-acetylglucosaminylation, protein kinase C phosphorylation, and methylglyoxal-induced unfolded protein response and NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome activation. Therapeutic prevention is achieved through activation of transcription factor nuclear factor erythroid 2-related factor 2, increasing the expression of glucose-6-phosphate (G6P) dehydrogenase, glyoxalase 1, and antioxidant enzymes. This diverts excess G6P to the pentose phosphate pathway, methylglyoxal to the glyoxalase pathway, and counters oxidative stress, respectively.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond waste: arginine metabolism and ammonium detoxification in cardiovascular–renal–metabolic disease 超越废物：心血管-肾脏代谢疾病中的精氨酸代谢和铵解毒
Trends in Endocrinology & Metabolism Pub Date : 2026-09-28 DOI: 10.1016/j.tem.2026.09.005
Lauren Peysakhova,Maria Chrysopoulou,Markus M. Rinschen
{"title":"Beyond waste: arginine metabolism and ammonium detoxification in cardiovascular–renal–metabolic disease","authors":"Lauren Peysakhova,Maria Chrysopoulou,Markus M. Rinschen","doi":"10.1016/j.tem.2026.09.005","DOIUrl":"https://doi.org/10.1016/j.tem.2026.09.005","url":null,"abstract":"Ammonium is a toxic product of amino acid degradation and protein turnover that is incorporated into arginine and detoxified via the urea cycle. Recent work has expanded the role of ammonium detoxification and the urea cycle toward broader metabolic functions. This review examines how ammonium and urea cycle-related metabolites function beyond nitrogen disposal and work as bioactive regulators across the cardiovascular, renal, and metabolic disease spectrum. We discuss how interorgan coordination among the gut, liver, kidney, heart, and immune system links arginine metabolism, ammonium detoxification, and metabolic signaling. Evidence suggests that ammonium can influence mitochondrial function, inflammatory tone, and tissue remodeling. The review considers how noncanonical urea cycle activity may contribute to chronic kidney disease, heart failure, and metabolic dysfunction.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149067330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Current antiretrovirals, hyperglycemia, and type 2 diabetes in people with HIV 目前艾滋病毒感染者的抗逆转录病毒药物、高血糖和2型糖尿病
Trends in Endocrinology & Metabolism Pub Date : 2026-09-24 DOI: 10.1016/j.tem.2026.09.001
Megan Farminer,Véronique Béréziat,Ghislaine Guillemain,Bruno Fève,Claire Lagathu,Jacqueline Capeau
{"title":"Current antiretrovirals, hyperglycemia, and type 2 diabetes in people with HIV","authors":"Megan Farminer,Véronique Béréziat,Ghislaine Guillemain,Bruno Fève,Claire Lagathu,Jacqueline Capeau","doi":"10.1016/j.tem.2026.09.001","DOIUrl":"https://doi.org/10.1016/j.tem.2026.09.001","url":null,"abstract":"People with HIV (PWH) are now effectively treated with antiretroviral therapy, including integrase strand transfer inhibitors (INSTIs) and nucleoside reverse transcriptase inhibitors (NRTIs). In the context of the global obesity epidemic, cardiometabolic complications, including type 2 diabetes, are increasingly common in PWH. In this article, we address the potential diabetogenic role of some current antiretrovirals. Beyond classical risk factors, INSTIs could promote diabetes through weight gain and drug-specific effects. They can also, rarely, induce severe acute ketosis-prone hyperglycemia. Because INSTIs and some NRTIs could alter insulin and lipid levels, standard indices of insulin resistance may be unreliable. Diabetes management generally follows recommendations for the general population, with the use of glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors to reduce glycated hemoglobin A1c, weight, and cardiometabolic risk.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149027544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
NAD+ augmentation in brain aging: hype, hope, or emerging reality? NAD+增强脑老化：炒作，希望，还是新兴的现实？
Trends in Endocrinology & Metabolism Pub Date : 2026-09-22 DOI: 10.1016/j.tem.2026.09.003
He-Ling Wang,Jianying Zhang,Evandro Fei Fang
{"title":"NAD+ augmentation in brain aging: hype, hope, or emerging reality?","authors":"He-Ling Wang,Jianying Zhang,Evandro Fei Fang","doi":"10.1016/j.tem.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.tem.2026.09.003","url":null,"abstract":"Restoring NAD+ to physiological levels shows promise for countering brain aging and neurodegeneration, backed by preclinical and growing clinical evidence. Key challenges remain: measurement validity, brain delivery, optimal dosing, and trial design. This forum examines current evidence, addresses ongoing controversies, and outlines priorities for future research and translation.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Itaconate Itaconate
Trends in Endocrinology & Metabolism Pub Date : 2026-09-09 DOI: 10.1016/j.tem.2026.07.012
Eva M. Pålsson-McDermott,Luke A.J. O’Neill
{"title":"Itaconate","authors":"Eva M. Pålsson-McDermott,Luke A.J. O’Neill","doi":"10.1016/j.tem.2026.07.012","DOIUrl":"https://doi.org/10.1016/j.tem.2026.07.012","url":null,"abstract":"","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148908786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The epigenetic and metabolic basis of obesity memory 肥胖记忆的表观遗传和代谢基础
Trends in Endocrinology & Metabolism Pub Date : 2026-09-01 DOI: 10.1016/j.tem.2026.09.011
Atrayee Gope,Michelangelo Certo,Sofia Vidali,Efthymios Ladoukakis,Andrew E. Hogan,Belinda Nedjai,Claudio Mauro
{"title":"The epigenetic and metabolic basis of obesity memory","authors":"Atrayee Gope,Michelangelo Certo,Sofia Vidali,Efthymios Ladoukakis,Andrew E. Hogan,Belinda Nedjai,Claudio Mauro","doi":"10.1016/j.tem.2026.09.011","DOIUrl":"https://doi.org/10.1016/j.tem.2026.09.011","url":null,"abstract":"","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Oxysterolome Iterative Metabolism Expands Sterol Signaling 甾体素迭代代谢扩展甾醇信号传导
Trends in Endocrinology & Metabolism Pub Date : 2026-09-01 DOI: 10.1016/j.tem.2026.09.010
Silia Ayadi,Julio Buñay,Sandrine Silvente-Poirot,Philippe de Medina,Marc Poirot
{"title":"The Oxysterolome Iterative Metabolism Expands Sterol Signaling","authors":"Silia Ayadi,Julio Buñay,Sandrine Silvente-Poirot,Philippe de Medina,Marc Poirot","doi":"10.1016/j.tem.2026.09.010","DOIUrl":"https://doi.org/10.1016/j.tem.2026.09.010","url":null,"abstract":"","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nitric oxide 一氧化氮
Trends in Endocrinology & Metabolism Pub Date : 2026-08-26 DOI: 10.1016/j.tem.2026.08.003
Roberta Albino dos Reis,Marina Diotallevi
{"title":"Nitric oxide","authors":"Roberta Albino dos Reis,Marina Diotallevi","doi":"10.1016/j.tem.2026.08.003","DOIUrl":"https://doi.org/10.1016/j.tem.2026.08.003","url":null,"abstract":"","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148821629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Butyrate 丁酸盐
Trends in Endocrinology & Metabolism Pub Date : 2026-08-26 DOI: 10.1016/j.tem.2026.08.004
Vitor R. Muñoz,Marco A.R. Vinolo
{"title":"Butyrate","authors":"Vitor R. Muñoz,Marco A.R. Vinolo","doi":"10.1016/j.tem.2026.08.004","DOIUrl":"https://doi.org/10.1016/j.tem.2026.08.004","url":null,"abstract":"","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148821561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neural regulation and manipulation of pancreatic β cells 胰腺β细胞的神经调节和操纵
Trends in Endocrinology & Metabolism Pub Date : 2026-08-21 DOI: 10.1016/j.tem.2026.08.001
Junta Imai,Hideki Katagiri
{"title":"Neural regulation and manipulation of pancreatic β cells","authors":"Junta Imai,Hideki Katagiri","doi":"10.1016/j.tem.2026.08.001","DOIUrl":"https://doi.org/10.1016/j.tem.2026.08.001","url":null,"abstract":"Pancreatic β cells are regulated by integrative neural signals beyond simple autonomic efferent control. Emerging evidence highlights the critical roles of afferent nerve signals and the gut–liver–brain–pancreas network in regulating β cells. Harnessing these intrinsic neural pathways may offer innovative therapeutic strategies for restoring β cell function and mass.","PeriodicalId":23301,"journal":{"name":"Trends in Endocrinology & Metabolism","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148768867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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