{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:58:51Z","timestamp":1778767131427,"version":"3.51.4"},"reference-count":34,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"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\/501100008208","name":"Overl\u00e6ge Johan Boserup og Lise Boserups Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008208","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,7,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Cholecystokinin (CCK) is a gut hormone originally known for its effects on gallbladder contraction and release of digestive enzymes. CCK, however, also mediates satiety and stimulate insulin secretion. Knowledge of the distribution of CCK-producing enteroendocrine cells (I cells) in humans is sparse. The general notion, based on animal data, is that I cells are present mainly in the proximal small intestine. We examined the occurrence of I cells (immunohistochemically) and the expression of CCK messenger RNA (mRNA) as well as CCK1 and CCK2 receptor mRNA along the intestines in healthy individuals and patients with type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mucosal biopsies collected with 30-cm intervals in the small intestine and from seven anatomical locations in the large intestine (using double-balloon enteroscopy) from 12 patients with type 2 diabetes and 12 gender-, age-, and body mass index\u2013matched healthy individuals were analyzed using mRNA sequencing and immunohistochemical staining.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed a gradual decrease in CCK mRNA expression and density of CCK-immunoreactive cells from duodenum to ileum. Very few CCK-immunoreactive cells and nearly undetectable CCK mRNA expression were found in the large intestine. No significant differences were seen between the groups. Expression of CCK receptors was observed in the duodenum of both groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Both density of CCK cells and expression of CCK mRNA decreased through the small intestine in both groups with low levels in the large intestine. Patients with type 2 diabetes did not have altered density of CCK cells or expression of CCK mRNA in intestinal mucosa.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgab367","type":"journal-article","created":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T07:22:31Z","timestamp":1622013751000},"page":"2164-2170","source":"Crossref","is-referenced-by-count":22,"title":["Expression of Cholecystokinin and its Receptors in the Intestinal Tract of Type 2 Diabetes Patients and Healthy Controls"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6999-1872","authenticated-orcid":false,"given":"Hannah","family":"Gilliam-Vigh","sequence":"first","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-5284","authenticated-orcid":false,"given":"Tina","family":"Jorsal","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens F","family":"Rehfeld","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4419-4911","authenticated-orcid":false,"given":"Steen S","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Vilsb\u00f8ll","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Steno Diabetes Center Copenhagen, Gentofte, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-5034","authenticated-orcid":false,"given":"Filip K","family":"Knop","sequence":"additional","affiliation":[{"name":"Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"Steno Diabetes Center Copenhagen, Gentofte, Denmark"},{"name":"Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Gentofte, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"issue":"3","key":"2021122204431539800_CIT0001","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1152\/ajplegacy.1928.86.3.599","article-title":"A hormone mechanism for gall-bladder contraction and evacuation","volume":"86","author":"Ivy","year":"1928","journal-title":"Am J Physiol Content"},{"key":"2021122204431539800_CIT0002","first-page":"337","article-title":"Cholecystokinin.","volume-title":"Handbook of Physiology","author":"Rehfeld","year":"1989"},{"issue":"3","key":"2021122204431539800_CIT0003","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1042\/cs0690259","article-title":"Human pancreatic and biliary responses to physiological concentrations of cholecystokinin octapeptide","volume":"69","author":"Anagnostides","year":"1985","journal-title":"Clin Sci (Lond)."},{"issue":"1","key":"2021122204431539800_CIT0004","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1152\/ajplegacy.1967.213.1.215","article-title":"Enhancement of pancreatic enzyme synthesis by pancreozymin","volume":"213","author":"Rothman","year":"1967","journal-title":"Am J Physiol."},{"key":"2021122204431539800_CIT0005","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fendo.2017.00047","article-title":"Cholecystokinin-from local gut hormone to ubiquitous messenger","volume":"8","author":"Rehfeld","year":"2017","journal-title":"Front Endocrinol (Lausanne)."},{"issue":"3","key":"2021122204431539800_CIT0006","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0143-4179(98)90041-5","article-title":"Modulation of murine lymphocyte functions by sulfated cholecystokinin octapeptide","volume":"32","author":"De La Fuente","year":"1998","journal-title":"Neuropeptides"},{"issue":"5751","key":"2021122204431539800_CIT0007","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/284033a0","article-title":"Neural regulation of pancreatic hormone secretion by the C-terminal tetrapeptide of CCK","volume":"284","author":"Rehfeld","year":"1980","journal-title":"Nature."},{"issue":"1","key":"2021122204431539800_CIT0008","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S0016-5085(03)00697-8","article-title":"Distribution of CCK1 and CCK2 receptors in normal and diseased human pancreatic tissue","volume":"125","author":"Reubi","year":"2003","journal-title":"Gastroenterology."},{"issue":"5424","key":"2021122204431539800_CIT0009","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/245323a0","article-title":"Cholecystokinin elicits satiety in rats with open gastric fistulas","volume":"245","author":"Gibbs","year":"1973","journal-title":"Nature."},{"issue":"2","key":"2021122204431539800_CIT0010","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1111\/dom.13080","article-title":"The bile acid-sequestering resin sevelamer eliminates the acute GLP-1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes","volume":"20","author":"Br\u00f8nden","year":"2018","journal-title":"Diabetes, Obes Metab"},{"issue":"5","key":"2021122204431539800_CIT0011","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1210\/jc.2016-1133","article-title":"Cholecystokinin-induced gallbladder emptying and metformin elicit additive glucagon-like peptide-1 responses","volume":"101","author":"Rohde","year":"2016","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122204431539800_CIT0012","first-page":"489","article-title":"Reduced postprandial cholecystokinin (CCK) secretion in patients with noninsulin-dependent diabetes mellitus: evidence for a role for CCK in regulating postprandial hyperglycemia","volume":"76","author":"Rushakoff","year":"1993","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122204431539800_CIT0013","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1530\/EJE-14-0309","article-title":"Postprandial gallbladder emptying in patients with type 2 diabetes: potential implications for bile-induced secretion of glucagon-like peptide 1","volume":"171","author":"Sonne","year":"2014","journal-title":"Eur J Endocrinol."},{"issue":"1 Pt 1","key":"2021122204431539800_CIT0014","first-page":"E40","article-title":"Cholecystokinin receptors and vagal nerves in control of food intake in rats","volume":"258","author":"Garlicki","year":"1990","journal-title":"Am J Physiol."},{"issue":"6","key":"2021122204431539800_CIT0015","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.peptides.2011.03.017","article-title":"The short term satiety peptide cholecystokinin reduces meal size and prolongs intermeal interval","volume":"32","author":"Lateef","year":"2011","journal-title":"Peptides."},{"key":"2021122204431539800_CIT0016","first-page":"277","article-title":"The role of cholecystokinin receptors in the short-term control of food intake.","volume-title":"Progress in Molecular Biology and Translational Science","author":"Sayegh","year":"2013"},{"issue":"2","key":"2021122204431539800_CIT0017","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol Cell Proteomics."},{"issue":"5","key":"2021122204431539800_CIT0018","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/S0016-5085(83)80080-8","article-title":"Endocrine cells in human intestine: an immunocytochemical study","volume":"85","author":"Sj\u00f6lund","year":"1983","journal-title":"Gastroenterology"},{"issue":"2","key":"2021122204431539800_CIT0019","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1007\/s00125-017-4450-9","article-title":"Enteroendocrine K and L cells in healthy and type 2 diabetic individuals","volume":"61","author":"Jorsal","year":"2018","journal-title":"Diabetologia."},{"issue":"9","key":"2021122204431539800_CIT0020","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.3109\/00365521.2014.934912","article-title":"The use of double-balloon enteroscopy in retrieving mucosal biopsies from the entire human gastrointestinal tract","volume":"49","author":"Rhee","year":"2014","journal-title":"Scand J Gastroenterol."},{"issue":"1-2","key":"2021122204431539800_CIT0021","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0009-8981(94)90228-3","article-title":"A processing-independent assay for human procholecystokinin and its products","volume":"229","author":"Paloheimo","year":"1994","journal-title":"Clin Chim Acta"},{"key":"2021122204431539800_CIT0022"},{"issue":"1","key":"2021122204431539800_CIT0023","first-page":"251","article-title":"The predominant cholecystokinin in human plasma and intestine is cholecystokinin-33","volume":"86","author":"Rehfeld","year":"2001","journal-title":"J Clin Endocrinol Metab."},{"issue":"12","key":"2021122204431539800_CIT0024","doi-asserted-by":"crossref","first-page":"5782","DOI":"10.1210\/en.2012-1595","article-title":"A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin","volume":"153","author":"Egerod","year":"2012","journal-title":"Endocrinology."},{"issue":"5","key":"2021122204431539800_CIT0025","doi-asserted-by":"crossref","DOI":"10.1210\/endrev\/bnaa018","article-title":"Enteroendocrine dynamics - new tools reveal hormonal plasticity in the gut","volume":"41","author":"Beumer","year":"2020","journal-title":"Endocr Rev"},{"issue":"5","key":"2021122204431539800_CIT0026","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."},{"key":"2021122204431539800_CIT0027","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.peptides.2015.07.010","article-title":"Nonsulfated cholecystokinins in the small intestine of pigs and rats","volume":"71","author":"Agersnap","year":"2015","journal-title":"Peptides."},{"issue":"2","key":"2021122204431539800_CIT0028","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00441-017-2612-1","article-title":"Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine","volume":"369","author":"Fakhry","year":"2017","journal-title":"Cell Tissue Res."},{"issue":"8","key":"2021122204431539800_CIT0029","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1136\/gut.20.8.653","article-title":"Distribution of the gut hormones in the primate intestinal tract","volume":"20","author":"Bryant","year":"1979","journal-title":"Gut."},{"issue":"2","key":"2021122204431539800_CIT0030","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s00441-016-2530-7","article-title":"Analysis of enteroendocrine cell populations in the human colon","volume":"367","author":"Martins","year":"2017","journal-title":"Cell Tissue Res."},{"issue":"1","key":"2021122204431539800_CIT0031","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1097\/MED.0b013e32834eb77d","article-title":"Cholecystokinin","volume":"19","author":"Dockray","year":"2012","journal-title":"Curr Opin Endocrinol Diabetes Obes."},{"issue":"7","key":"2021122204431539800_CIT0032","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1007\/s11695-012-0621-4","article-title":"Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects","volume":"22","author":"Jacobsen","year":"2012","journal-title":"Obes Surg."},{"issue":"1 Pt 2","key":"2021122204431539800_CIT0033","first-page":"R110","article-title":"Intraduodenal infusions of fats elicit satiety in sham-feeding rats","volume":"259","author":"Greenberg","year":"1990","journal-title":"Am J Physiol"},{"issue":"2 Pt 1","key":"2021122204431539800_CIT0034","first-page":"G243","article-title":"Proteins but not amino acids, carbohydrates, or fats stimulate cholecystokinin secretion in the rat","volume":"251","author":"Liddle","year":"1986","journal-title":"Am J Physiol."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgab367\/38826432\/dgab367.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/8\/2164\/41848351\/dgab367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/106\/8\/2164\/41848351\/dgab367.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T04:47:55Z","timestamp":1640148475000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/106\/8\/2164\/6283726"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,24]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,5,24]]},"published-print":{"date-parts":[[2021,7,13]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgab367","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,8,1]]},"published":{"date-parts":[[2021,5,24]]}}}