{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:41:00Z","timestamp":1774658460307,"version":"3.50.1"},"reference-count":89,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T00:00:00Z","timestamp":1658707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-14853"],"award-info":[{"award-number":["PJT-14853"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Foundation for Innovation and Ontario Research Fund","award":["project numbers 19442 and 30961"],"award-info":[{"award-number":["project numbers 19442 and 30961"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metabolism and circadian rhythms are intimately linked, with circadian glucagon-like peptide-1 (GLP-1) secretion by the intestinal L-cell entraining rhythmic insulin release. GLP-1 secretion has been explored in the context of obesogenic diets, but never in a rodent model of type 2 diabetes (T2D). There is also considerable disagreement regarding GLP-1 levels in human T2D. Furthermore, recent evidence has demonstrated decreased expression of the \u03b2-cell exocytotic protein secretagogin (SCGN) in T2D. To extend these findings to the L-cell, we administered oral glucose tolerance tests at 6 time points in 4-hour intervals to the high-fat diet\/streptozotocin (HFD-STZ) mouse model of T2D. This revealed a 10-fold increase in peak GLP-1 secretion with a phase shift of the peak from the normal feeding period into the fasting-phase. This was accompanied by impairments in the rhythms of glucose, glucagon, mucosal clock genes (Arntl and Cry2), and Scgn. Immunostaining revealed that L-cell GLP-1 intensity was increased in the HFD-STZ model, as was the proportion of L-cells that expressed SCGN; however, this was not found in L-cells from humans with T2D, which exhibited decreased GLP-1 staining but maintained their SCGN expression. Gcg expression in isolated L-cells was increased along with pathways relating to GLP-1 secretion and electron transport chain activity in the HFD-STZ condition. Further investigation into the mechanisms responsible for this increase in GLP-1 secretion may give insights into therapies directed toward upregulating endogenous GLP-1 secretion.<\/jats:p>","DOI":"10.1210\/endocr\/bqac118","type":"journal-article","created":{"date-parts":[[2022,7,25]],"date-time":"2022-07-25T11:11:25Z","timestamp":1658747485000},"source":"Crossref","is-referenced-by-count":11,"title":["Disrupted and Elevated Circadian Secretion of Glucagon-Like Peptide-1 in a Murine Model of Type 2 Diabetes"],"prefix":"10.1210","volume":"163","author":[{"given":"Andrew D","family":"Biancolin","sequence":"first","affiliation":[{"name":"Departments of Physiology, University of Toronto , Toronto ON M5S 1A8 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyerin","family":"Jeong","sequence":"additional","affiliation":[{"name":"Departments of Physiology, University of Toronto , Toronto ON M5S 1A8 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly W Y","family":"Mak","sequence":"additional","affiliation":[{"name":"Departments of Physiology, University of Toronto , Toronto ON M5S 1A8 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zixuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Departments of Physiology, University of Toronto , Toronto ON M5S 1A8 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-788X","authenticated-orcid":false,"given":"Patricia L","family":"Brubaker","sequence":"additional","affiliation":[{"name":"Departments of Physiology, University of Toronto , Toronto ON M5S 1A8 , Canada"},{"name":"Department of Medicine, University of Toronto , Toronto ON M5S 1A8 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2022,7,25]]},"reference":[{"issue":"3","key":"2022081112390151100_CIT0001","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.cmet.2006.01.004","article-title":"The biology of incretin hormones","volume":"3","author":"Drucker","year":"2006","journal-title":"Cell Metab."},{"key":"2022081112390151100_CIT0002","first-page":"72","article-title":"Glucagon-like peptide 1 (GLP-1)","volume-title":"Mol. Metab.","author":"M\u00fcller","year":"2019"},{"issue":"6","key":"2022081112390151100_CIT0003","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.cmet.2013.04.008","article-title":"Pharmacology, physiology, and mechanisms of incretin hormone action","volume":"17","author":"Campbell","year":"2013","journal-title":"Cell Metab."},{"issue":"12","key":"2022081112390151100_CIT0004","doi-asserted-by":"crossref","first-page":"4217","DOI":"10.1172\/JCI97233","article-title":"Discovery, characterization, and clinical development of the glucagon-like peptides","volume":"127","author":"Drucker","year":"2017","journal-title":"J Clin Invest."},{"issue":"11","key":"2022081112390151100_CIT0005","doi-asserted-by":"crossref","first-page":"3674","DOI":"10.2337\/db13-1501","article-title":"Circadian secretion of the intestinal hormone GLP-1 by the rodent L cell","volume":"63","author":"Gil-Lozano","year":"2014","journal-title":"Diabetes."},{"key":"2022081112390151100_CIT0006","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.molmet.2019.11.004","article-title":"The core clock gene, Bmal1, and its downstream target, the SNARE regulatory protein secretagogin, are necessary for circadian secretion of glucagon-like peptide-1","volume":"31","author":"Biancolin","year":"2020","journal-title":"Mol Metab."},{"issue":"12","key":"2022081112390151100_CIT0007","doi-asserted-by":"crossref","first-page":"258","DOI":"10.2337\/db20-0262","article-title":"Circadian GLP-1 secretion in mice is dependent on the intestinal microbiome for maintenance of diurnal metabolic homeostasis","volume":"69","author":"Martchenko","year":"2020","journal-title":"Diabetes."},{"issue":"6315","key":"2022081112390151100_CIT0008","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1126\/science.aah4965","article-title":"Circadian time signatures of fitness and disease","volume":"354","author":"Bass","year":"2016","journal-title":"Science."},{"issue":"217","key":"2022081112390151100_CIT0009","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-3-642-25950-0_1","article-title":"Molecular components of the mammalian circadian clock","volume":"217","author":"Buhr","year":"2013","journal-title":"Handb Exp Pharmacol."},{"issue":"2","key":"2022081112390151100_CIT0010","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.molcel.2012.06.026","article-title":"Clocks, metabolism, and the epigenome","volume":"47","author":"Feng","year":"2012","journal-title":"Mol Cell."},{"issue":"1","key":"2022081112390151100_CIT0011","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1146\/annurev-neuro-060909-153128","article-title":"Central and peripheral circadian clocks in mammals","volume":"35","author":"Mohawk","year":"2012","journal-title":"Annu Rev Neurosci."},{"issue":"4","key":"2022081112390151100_CIT0012","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nrgastro.2016.8","article-title":"Circadian rhythms of liver physiology and disease: experimental and clinical evidence","volume":"13","author":"Tahara","year":"2016","journal-title":"Nat Rev Gastroenterol Hepatol."},{"issue":"2","key":"2022081112390151100_CIT0013","doi-asserted-by":"crossref","first-page":"399","DOI":"10.3945\/an.115.010777","article-title":"Circadian rhythms, metabolism, and chrononutrition in rodents and humans","volume":"7","author":"Johnston","year":"2016","journal-title":"Adv Nutr."},{"issue":"4","key":"2022081112390151100_CIT0014","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1053\/j.gastro.2007.07.009","article-title":"Clock gene expression in the murine gastrointestinal tract: Endogenous rhythmicity and effects of a feeding regimen","volume":"133","author":"Hoogerwerf","year":"2007","journal-title":"Gastroenterology."},{"key":"2022081112390151100_CIT0015","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/dom.12517","article-title":"Skeletal muscle functions around the clock","volume":"17","author":"Mayeuf-Louchart","year":"2015","journal-title":"Diabetes Obes Metab."},{"issue":"7306","key":"2022081112390151100_CIT0016","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/nature09253","article-title":"Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes","volume":"466","author":"Marcheva","year":"2010","journal-title":"Nature."},{"issue":"2","key":"2022081112390151100_CIT0017","doi-asserted-by":"crossref","first-page":"e1000595","DOI":"10.1371\/journal.pbio.1000595","article-title":"Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver. Kramer A, ed","volume":"9","author":"Rey","year":"2011","journal-title":"PLoS Biol."},{"issue":"6105","key":"2022081112390151100_CIT0018","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1126\/science.1226339","article-title":"Transcriptional architecture and chromatin landscape of the core circadian clock in mammals","volume":"338","author":"Koike","year":"2012","journal-title":"Science."},{"issue":"1","key":"2022081112390151100_CIT0019","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1152\/physiolgenomics.00066.2007","article-title":"Identification of the circadian transcriptome in adult mouse skeletal muscle","volume":"31","author":"McCarthy","year":"2007","journal-title":"Physiol Genomics."},{"issue":"4","key":"2022081112390151100_CIT0020","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2337\/diabetes.55.04.06.db05-0873","article-title":"Characterization of peripheral circadian clocks in adipose tissues","volume":"55","author":"Zvonic","year":"2006","journal-title":"Diabetes."},{"issue":"5","key":"2022081112390151100_CIT0021","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1210\/en.2017-00218","article-title":"Glucose homeostasis: regulation by peripheral circadian clocks in rodents and humans","volume":"158","author":"Gachon","year":"2017","journal-title":"Endocrinology."},{"key":"2022081112390151100_CIT0022","doi-asserted-by":"crossref","first-page":"k4641","DOI":"10.1136\/bmj.k4641","article-title":"Rotating night shift work and adherence to unhealthy lifestyle in predicting risk of type 2 diabetes: results from two large US cohorts of female nurses","volume":"363","author":"Shan","year":"2018","journal-title":"BMJ."},{"issue":"12","key":"2022081112390151100_CIT0023","doi-asserted-by":"crossref","first-page":"e1001141","DOI":"10.1371\/journal.pmed.1001141","article-title":"Rotating night shift work and risk of type 2 diabetes: Two prospective cohort studies in women. Groop L, ed","volume":"8","author":"Pan","year":"2011","journal-title":"PLoS Med."},{"issue":"6","key":"2022081112390151100_CIT0024","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1093\/ije\/dyy079","article-title":"Is shift work associated with a higher risk of overweight or obesity? A systematic review of observational studies with meta-analysis","volume":"47","author":"Liu","year":"2018","journal-title":"Int J Epidemiol."},{"issue":"1","key":"2022081112390151100_CIT0025","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1017\/S0954422410000016","article-title":"Obesity and shift work: chronobiological aspects","volume":"23","author":"Antunes","year":"2010","journal-title":"Nutr Res Rev."},{"issue":"5","key":"2022081112390151100_CIT0026","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cmet.2007.09.006","article-title":"High-fat diet disrupts behavioral and molecular circadian rhythms in mice","volume":"6","author":"Kohsaka","year":"2007","journal-title":"Cell Metab."},{"issue":"2","key":"2022081112390151100_CIT0027","article-title":"Altered circadian responses to light in streptozotocin-induced diabetic mice","volume":"277","author":"Challet","year":"1999","journal-title":"Am J Physiol."},{"issue":"2","key":"2022081112390151100_CIT0028","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1152\/physiol.00003.2018","article-title":"Circadian etiology of type 2 diabetes mellitus","volume":"33","author":"Javeed","year":"2018","journal-title":"Physiology."},{"key":"2022081112390151100_CIT0029","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.biochi.2015.06.029","article-title":"Circadian phenotyping of obese and diabetic db\/db mice","volume":"124","author":"Grosbellet","year":"2016","journal-title":"Biochimie."},{"issue":"43","key":"2022081112390151100_CIT0030","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abi9654","article-title":"Disrupted circadian oscillations in type 2 diabetes are linked to altered rhythmic mitochondrial metabolism in skeletal muscle","volume":"7","author":"Gabriel","year":"2021","journal-title":"Sci Adv."},{"issue":"5","key":"2022081112390151100_CIT0031","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1073\/pnas.1916539117","article-title":"In pancreatic islets from type 2 diabetes patients, the dampened circadian oscillators lead to reduced insulin and glucagon exocytosis","volume":"117","author":"Petrenko","year":"2020","journal-title":"Proc Natl Acad Sci USA."},{"issue":"2","key":"2022081112390151100_CIT0032","doi-asserted-by":"crossref","first-page":"242","DOI":"10.2337\/diacare.3.2.242","article-title":"Glucose and insulin response to high carbohydrate meals in normal and maturity-onset diabetic subjects","volume":"3","author":"Schade","year":"1980","journal-title":"Diabetes Care."},{"issue":"7","key":"2022081112390151100_CIT0033","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1016\/j.metabol.2011.11.013","article-title":"Regulation of core clock genes in human islets","volume":"61","author":"Stamenkovic","year":"2012","journal-title":"Metabolism."},{"issue":"16","key":"2022081112390151100_CIT0034","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1001\/archinte.166.16.1768","article-title":"Role of sleep duration and quality in the risk and severity of type 2 diabetes mellitus","volume":"166","author":"Knutson","year":"2006","journal-title":"Arch Intern Med."},{"issue":"129","key":"2022081112390151100_CIT0035","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3003200","article-title":"Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption","volume":"4","author":"Buxton","year":"2012","journal-title":"Sci Transl Med."},{"issue":"36","key":"2022081112390151100_CIT0036","doi-asserted-by":"crossref","first-page":"14412","DOI":"10.1073\/pnas.0703247104","article-title":"Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes","volume":"104","author":"Woon","year":"2007","journal-title":"Proc Natl Acad Sci"},{"issue":"12","key":"2022081112390151100_CIT0037","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqaa167","article-title":"Circadian rhythms and the gastrointestinal tract: Relationship to metabolism and gut hormones","volume":"161","author":"Martchenko","year":"2020","journal-title":"Endocrinology."},{"issue":"4","key":"2022081112390151100_CIT0038","doi-asserted-by":"crossref","first-page":"e13007","DOI":"10.1111\/apha.13007","article-title":"Suppression of circadian secretion of glucagon-like peptide-1 by the saturated fatty acid, palmitate","volume":"222","author":"Martchenko","year":"2018","journal-title":"Acta Physiol."},{"issue":"1","key":"2022081112390151100_CIT0039","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.1038\/s41598-022-11223-7","article-title":"Nobiletin ameliorates high fat-induced disruptions in rhythmic glucagon-like peptide-1 secretion","volume":"12","author":"Martchenko","year":"2022","journal-title":"Sci Rep."},{"issue":"5","key":"2022081112390151100_CIT0040","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqaa039","article-title":"Essential role of syntaxin-binding protein-1 in the regulation of glucagon-like peptide-1 secretion","volume":"161","author":"Campbell","year":"2020","journal-title":"Endocrinology."},{"issue":"4","key":"2022081112390151100_CIT0041","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1101\/gad.290379.116","article-title":"Pancreatic \u03b1- and \u03b2-cellular clocks have distinct molecular properties and impact on islet hormone secretion and gene expression","volume":"31","author":"Petrenko","year":"2017","journal-title":"Genes Dev."},{"issue":"14","key":"2022081112390151100_CIT0042","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.15252\/embj.201695347","article-title":"A TRPV1-to-secretagogin regulatory axis controls pancreatic \u03b2-cell survival by modulating protein turnover","volume":"36","author":"Malenczyk","year":"2017","journal-title":"EMBO J."},{"issue":"1","key":"2022081112390151100_CIT0043","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/s41598-017-00344-z","article-title":"SUMOylation and calcium control syntaxin-1A and secretagogin sequestration by tomosyn to regulate insulin exocytosis in human \u00df cells","volume":"7","author":"Ferdaoussi","year":"2017","journal-title":"Sci Rep."},{"issue":"1","key":"2022081112390151100_CIT0044","doi-asserted-by":"crossref","first-page":"6976","DOI":"10.1038\/s41598-017-07072-4","article-title":"Calcium ion induced structural changes promote dimerization of secretagogin, which is required for its insulin secretory function","volume":"7","author":"Lee","year":"2017","journal-title":"Sci Rep."},{"issue":"5","key":"2022081112390151100_CIT0045","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.cell.2018.12.029","article-title":"Identification of enteroendocrine regulators by real-time single-cell differentiation mapping","volume":"176","author":"Gehart","year":"2019","journal-title":"Cell."},{"issue":"6","key":"2022081112390151100_CIT0046","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.cell.2020.04.036","article-title":"High-resolution mRNA and secretome atlas of human enteroendocrine cells","volume":"181","author":"Beumer","year":"2020","journal-title":"Cell."},{"key":"2022081112390151100_CIT0047","doi-asserted-by":"crossref","DOI":"10.1016\/j.jcmgh.2022.02.007","article-title":"A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics","author":"Burclaff","year":"2022","journal-title":"Cell Mol Gastroenterol Hepatol."},{"key":"2022081112390151100_CIT0048","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.49910","article-title":"SCGN deficiency results in colitis susceptibility","volume":"8","author":"Sifuentes-Dominguez","year":"2019","journal-title":"Elife."},{"issue":"12","key":"2022081112390151100_CIT0049","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1042\/BCJ20160137","article-title":"Secretagogin affects insulin secretion in pancreatic \u03b2-cells by regulating actin dynamics and focal adhesion","volume":"473","author":"Yang","year":"2016","journal-title":"Biochem J."},{"issue":"1","key":"2022081112390151100_CIT0050","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1042\/BJ20060918","article-title":"Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin","volume":"401","author":"Rogstam","year":"2007","journal-title":"Biochem J."},{"issue":"6","key":"2022081112390151100_CIT0051","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.cmet.2008.11.002","article-title":"Glucose sensing in L cells: A primary cell study","volume":"8","author":"Reimann","year":"2008","journal-title":"Cell Metab."},{"issue":"3 Pt 1","key":"2022081112390151100_CIT0052","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1164\/ajrccm.163.3.2007120","article-title":"The impact of insulin-dependent diabetes on ventilatory control in the mouse","volume":"163","author":"Polotsky","year":"2001","journal-title":"Am J Respir Crit Care Med."},{"key":"2022081112390151100_CIT0053","doi-asserted-by":"crossref","DOI":"10.1016\/j.molmet.2021.101340","article-title":"L-cell Arntl is required for rhythmic glucagon-like peptide-1 secretion and maintenance of intestinal homeostasis","volume":"54","author":"Martchenko","year":"2021","journal-title":"Mol Metab."},{"key":"2022081112390151100_CIT0054","author":"Biancolin"},{"issue":"4","key":"2022081112390151100_CIT0055","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2212\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods."},{"issue":"5","key":"2022081112390151100_CIT0056","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nat Biotechnol."},{"key":"2022081112390151100_CIT0057","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.7563.1","article-title":"Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2015","journal-title":"F1000Research."},{"issue":"1","key":"2022081112390151100_CIT0058","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: a Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics."},{"key":"2022081112390151100_CIT0059","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/0-387-29362-0_23","article-title":"Limma: Linear models for microarray data.","volume-title":"Bioinformatics and Computational Biology Solutions Using R and Bioconductor","author":"Smyth","year":"2005"},{"issue":"2","key":"2022081112390151100_CIT0060","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41596-018-0103-9","article-title":"Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap","volume":"14","author":"Reimand","year":"2019","journal-title":"Nat Protoc."},{"issue":"11","key":"2022081112390151100_CIT0061","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0013984","article-title":"Enrichment map: a network-based method for gene-set enrichment visualization and interpretation","volume":"5","author":"Merico","year":"2010","journal-title":"PLoS One."},{"key":"2022081112390151100_CIT0062","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.9090.1","article-title":"AutoAnnotate: a cytoscape app for summarizing networks with semantic annotations","volume":"5","author":"Kucera","year":"2016","journal-title":"F1000Research."},{"issue":"21","key":"2022081112390151100_CIT0063","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1093\/bioinformatics\/btw405","article-title":"MetaCycle: an integrated R package to evaluate periodicity in large scale data","volume":"32","author":"Wu","year":"2016","journal-title":"Bioinformatics."},{"issue":"4","key":"2022081112390151100_CIT0064","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1093\/bioinformatics\/btz730","article-title":"CircaCompare: a method to estimate and statistically support differences in mesor, amplitude and phase, between circadian rhythms. Valencia A, ed","volume":"36","author":"Parsons","year":"2019","journal-title":"Bioinformatics."},{"key":"2022081112390151100_CIT0065","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.molmet.2018.05.019","article-title":"Secretagogin protects pdx1 from proteasomal degradation to control a transcriptional program required for \u03b2 cell specification","volume":"14","author":"Malenczyk","year":"2018","journal-title":"Mol Metab."},{"issue":"2","key":"2022081112390151100_CIT0066","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1021\/acs.biochem.6b00761","article-title":"Secretagogin is a redox-responsive Ca 2+ sensor","volume":"56","author":"Khandelwal","year":"2017","journal-title":"Biochemistry."},{"issue":"4","key":"2022081112390151100_CIT0067","article-title":"Intestinal growth is associated with elevated levels of glucagon-like peptide 2 in diabetic rats","volume":"273","author":"Fischer","year":"1997","journal-title":"Am J Physiol."},{"key":"2022081112390151100_CIT0068","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.peptides.2015.06.006","article-title":"High fat diet impairs the function of glucagon-like peptide-1 producing L-cells","volume":"77","author":"Richards","year":"2016","journal-title":"Peptides."},{"issue":"5","key":"2022081112390151100_CIT0069","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s00125-009-1288-9","article-title":"Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion","volume":"52","author":"Mingrone","year":"2009","journal-title":"Diabetologia."},{"issue":"9","key":"2022081112390151100_CIT0070","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/s42255-021-00458-9","article-title":"Diet-induced alteration of intestinal stem cell function underlies obesity and prediabetes in mice","volume":"3","author":"Aliluev","year":"2021","journal-title":"Nat Metab"},{"issue":"1","key":"2022081112390151100_CIT0071","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-017-0507-4","article-title":"Sox9 transcriptionally regulates Wnt signaling in intestinal epithelial stem cells in hypomethylated crypts in the diabetic state","volume":"8","author":"Huang","year":"2017","journal-title":"Stem Cell Res Ther."},{"issue":"2","key":"2022081112390151100_CIT0072","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.jcmgh.2020.08.006","article-title":"Reduced neurog3 gene dosage shifts enteroendocrine progenitor towards goblet cell lineage in the mouse intestine","volume":"11","author":"Li","year":"2021","journal-title":"Cell Mol Gastroenterol Hepatol."},{"issue":"6","key":"2022081112390151100_CIT0073","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1111\/dgd.12226","article-title":"Lgr5 positive stem cells sorted from small intestines of diabetic mice differentiate into higher proportion of absorptive cells and Paneth cells in vitro","volume":"57","author":"Zhong","year":"2015","journal-title":"Dev Growth Differ."},{"key":"2022081112390151100_CIT0074","first-page":"909","article-title":"Enteroendocrine cells switch hormone expression along the crypt-to-villus BMP signalling gradient","volume-title":"Nat Cell Biol.","author":"Beumer","year":"2018"},{"issue":"4","key":"2022081112390151100_CIT0075","article-title":"Antagonizing somatostatin receptor subtype 2 and 5 reduces blood glucose in a gut- and GLP-1R-dependent manner","volume":"6","author":"Jepsen","year":"2021","journal-title":"JCI Insight."},{"issue":"1","key":"2022081112390151100_CIT0076","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.yexcr.2015.05.022","article-title":"Differential molecular and cellular responses of GLP-1 secreting L-cells and pancreatic alpha cells to glucotoxicity and lipotoxicity","volume":"336","author":"Vasu","year":"2015","journal-title":"Exp Cell Res."},{"key":"2022081112390151100_CIT0077","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3389\/fendo.2021.650158","article-title":"Pathological \u03b2-cell endoplasmic reticulum stress in type 2 diabetes: current evidence","volume":"12","author":"Shrestha","year":"2021","journal-title":"Front Endocrinol (Lausanne)."},{"issue":"4","key":"2022081112390151100_CIT0078","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1210\/jcem.84.4.5612","article-title":"Type 2 diabetes mellitus: update on diagnosis, pathophysiology, and treatment","volume":"84","author":"Mahler","year":"1999","journal-title":"J Clin Endocrinol Metab."},{"issue":"17","key":"2022081112390151100_CIT0079","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/ijms21176275","article-title":"Pathophysiology of type 2 diabetes mellitus","volume":"21","author":"Galicia-Garcia","year":"2020","journal-title":"Int J Mol Sci."},{"issue":"6","key":"2022081112390151100_CIT0080","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1096\/fj.12-226092","article-title":"The hydrolase DDAH2 enhances pancreatic insulin secretion by transcriptional regulation of secretagogin through a Sirt1-dependent mechanism in mice","volume":"27","author":"Hasegawa","year":"2013","journal-title":"FASEB J."},{"issue":"1","key":"2022081112390151100_CIT0081","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s00125-010-1896-4","article-title":"Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: What is up, what is down?","volume":"54","author":"Nauck","year":"2011","journal-title":"Diabetologia."},{"issue":"3","key":"2022081112390151100_CIT0082","doi-asserted-by":"crossref","first-page":"678","DOI":"10.2337\/db07-1124","article-title":"Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance","volume":"57","author":"Vollmer","year":"2008","journal-title":"Diabetes."},{"issue":"2","key":"2022081112390151100_CIT0083","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1210\/jc.2011-2561","article-title":"Defects in GLP-1 response to an oral challenge do not play a significant role in the pathogenesis of prediabetes","volume":"97","author":"Smushkin","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2022081112390151100_CIT0084","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s00125-008-0951-x","article-title":"Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of pancreatic alpha and beta cell function but differential roles of incretin hormones and insulin action","volume":"51","author":"F\u00e6rch","year":"2008","journal-title":"Diabetologia."},{"key":"2022081112390151100_CIT0085","doi-asserted-by":"crossref","DOI":"10.1210\/clinem\/dgac095","article-title":"Incretin hypersecretion in gestational diabetes mellitus","author":"Fritsche","year":"2022","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2022081112390151100_CIT0086","doi-asserted-by":"crossref","first-page":"e78","DOI":"10.1002\/cpz1.78","article-title":"Streptozotocin-Induced Diabetic Models in Mice and Rats","volume":"1","author":"Furman","year":"2021","journal-title":"Curr Protoc."},{"issue":"3","key":"2022081112390151100_CIT0087","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/ilar.47.3.186","article-title":"Animal models of type 2 diabetes: clinical presentation and pathophysiological relevance to the human condition","volume":"47","author":"Cefalu","year":"2006","journal-title":"ILAR J."},{"issue":"4","key":"2022081112390151100_CIT0088","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0031-9384(97)00493-9","article-title":"Circadian control of insulin secretion Is independent of the temporal distribution of feeding","volume":"63","author":"Kalsbeek","year":"1998","journal-title":"Physiol Behav."},{"issue":"7","key":"2022081112390151100_CIT0089","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1007\/s00125-016-3955-y","article-title":"Glucagon: acute actions on hepatic metabolism","volume":"59","author":"Miller","year":"2016","journal-title":"Diabetologia."}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqac118\/45055921\/bqac118.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/163\/9\/bqac118\/45333242\/bqac118.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/163\/9\/bqac118\/45333242\/bqac118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,12]],"date-time":"2023-02-12T14:00:11Z","timestamp":1676210411000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqac118\/6649564"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,25]]},"references-count":89,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9,1]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqac118","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9,1]]},"published":{"date-parts":[[2022,7,25]]},"article-number":"bqac118"}}