Gene expression of nutrient-sensing molecules in I cells of CCK reporter male mice

in Journal of Molecular Endocrinology
Authors:
Tomoko Kato Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Norio Harada Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Eri Ikeguchi-Ogura Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Akiko Sankoda Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Tomonobu Hatoko Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Xuejing Lu Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Takuma Yasuda Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Shunsuke Yamane Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Nobuya Inagaki Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Kyoto, Japan

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Correspondence should be addressed to N Harada: nharada@kuhp.kyoto-u.ac.jp
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Cholecystokinin (CCK) is secreted from enteroendocrine I cells in response to fat, carbohydrate, and protein ingestion. Gene expression of nutrient-sensing molecules in I cells remains unclear, primarily due to the difficulty in distinguishing I cells from intestinal epithelial cells in vivo. In this study, we generated CCK reporter male mice in which the red fluorescence protein tdTomato (Tomato) is produced by activation of the native murine Cck promoter. Fluorescence microscopy revealed the presence of Tomato-positive cells in upper small intestine (SI), lower SI, and colon. Flow cytometer analysis revealed that Tomato-positive cells among epithelial cells of upper SI, lower SI, and colon occurred at the rate of 0.95, 0.54, and 0.06%, respectively. In upper SI and lower SI, expression levels of Cck mRNA were higher in Tomato-positive cells than those in Tomato-negative cells. The fatty acid receptors Gpr120, Gpr40, and Gpr43 and the oleoylethanolamide receptor Gpr119 were highly expressed in Tomato-positive cells isolated from SI, but were not found in Tomato-positive cells from colon. The glucose and fructose transporters Sglt1, Glut2, and Glut5 were expressed in both Tomato-positive cells and -negative cells, but these expression levels tended to be decreased in Tomato-positive cells from upper SI to colon. The peptide transporter Pept1 and receptor Gpr93 were expressed in both Tomato-positive cells and -negative cells, whereas Casr was expressed only in Tomato-positive cells isolated from SI. Thus, this transgenic mouse reveals that I cell number and gene expression in I cells vary according to region in the gastrointestinal tract.

 

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  • Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ & Ghatei MA et al. 2002 Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 418 650654. (https://doi.org/10.1038/nature00887)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brighton CA, Rievaj J, Kuhre RE, Glass LL, Schoonjans K, Holst JJ, Gribble FM & Reimann F 2015 Bile acids trigger GLP-1 release predominantly by accessing basolaterally located G protein-coupled bile acid receptors. Endocrinology 156 39613970. (https://doi.org/10.1210/en.2015-1321)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Choi S, Lee M, Shiu AL, Yo SJ, Halldén G & Aponte GW 2007 GPR93 activation by protein hydrolysate induces CCK transcription and secretion in STC-1 cells. American Journal of Physiology: Gastrointestinal and Liver Physiology 292 G1366G 1375. (https://doi.org/10.1152/ajpgi.00516.2006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • D’Agostino G, Lyons DJ, Cristiano C, Burke LK, Madara JC, Campbell JN, Garcia AP, Land BB, Lowell BB & Dileone RJ et al. 2016 Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. eLife 5 e12225. (https://doi.org/10.7554/eLife.12225)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Davis HR Jr, Mullins DE, Pines JM, Hoos LM, France CF, Compton DS, Graziano MP, Sybertz EJ, Strader CD & Van Heek M 1998 Effect of chronic central administration of glucagon-like peptide-1 (7–36) amide on food consumption and body weight in normal and obese rats. Obesity Research 6 147156. (https://doi.org/10.1002/j.1550-8528.1998.tb00329.x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Diakogiannaki E, Pais R, Tolhurst G, Parker HE, Horscroft J, Rauscher B, Zietek T, Daniel H, Gribble FM & Reimann F 2013 Oligopeptides stimulate glucagon-like peptide-1 secretion in mice through proton-coupled uptake and the calcium-sensing receptor. Diabetologia 56 26882696. (https://doi.org/10.1007/s00125-013-3037-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Egerod KL, Engelstoft MS, Grunddal KV, Nøhr MK, Secher A, Sakata I, Pedersen J, Windeløv JA, Füchtbauer EM & Olsen J et al. 2012 A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Endocrinology 153 57825795. (https://doi.org/10.1210/en.2012-1595)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Fakhry J, Wang J, Martins P, Fothergill LJ, Hunne B, Prieur P, Shulkes A, Rehfeld JF, Callaghan B & Furness JB 2017 Distribution and characterisation of CCK containing enteroendocrine cells of the mouse small and large intestine. Cell and Tissue Research 369 245253. (https://doi.org/10.1007/s00441-017-2612-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak MR & Wank SA 2010 Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion. PNAS 107 1779117796. (https://doi.org/10.1073/pnas.1009078107)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Gorboulev V, Schürmann A, Vallon V, Kipp H, Jaschke A, Klessen D, Friedrich A, Scherneck S, Rieg T & Cunard R et al. 2012 Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61 187196. (https://doi.org/10.2337/db11-1029)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Green GM, Taguchi S, Friestman J, Chey WY & Liddle RA 1989 Plasma secretin, CCK, and pancreatic secretion in response to dietary fat in the rat. American Journal of Physiology 256 G1016G 1021. (https://doi.org/10.1152/ajpgi.1989.256.6.G1016)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Habib AM, Richards P, Cairns LS, Rogers GJ, Bannon CAM, Parker HE, Morley TCE, Yeo GSH, Reimann F & Gribble FM 2012 Overlap of endocrine hormone expression in the mouse intestine revealed by transcriptional profiling and flow cytometry. Endocrinology 153 30543065. (https://doi.org/10.1210/en.2011-2170)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Harada N, Yamada Y, Tsukiyama K, Yamada C, Nakamura Y, Mukai E, Hamasaki A, Liu X, Toyoda K & Seino Y et al. 2008 A novel GIP receptor splice variant influences GIP sensitivity of pancreatic beta-cells in obese mice. American Journal of Physiology: Endocrinology and Metabolism 294 E61E 68. (https://doi.org/10.1152/ajpendo.00358.2007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hutchison AT, Feinle-Bisset C, Fitzgerald PC, Standfield S, Horowitz M, Clifton PM & Luscombe-Marsh ND 2015 Comparative effects of intraduodenal whey protein hydrolysate on antropyloroduodenal motility, gut hormones, glycemia, appetite, and energy intake in lean and obese men. American Journal of Clinical Nutrition 102 13231331. (https://doi.org/10.3945/ajcn.115.114538)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ikeguchi E, Harada N, Kanemaru Y, Sankoda A, Yamane S, Iwasaki K, Imajo M, Murata Y, Suzuki K & Joo E et al. 2018 Transcriptional factor Pdx1 is involved in age-related GIP hypersecretion in mice. American Journal of Physiology: Gastrointestinal and Liver Physiology 315 G272G282. (https://doi.org/10.1152/ajpgi.00054.2018)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Iwasaki K, Harada N, Sasaki K, Yamane S, Iida K, Suzuki K, Hamasaki A, Nasteska D, Shibue K & Joo E et al. 2015 Free fatty acid receptor GPR120 is highly expressed in enteroendocrine K cells of the upper small intestine and has a critical role in GIP secretion after fat ingestion. Endocrinology 156 837846. (https://doi.org/10.1210/en.2014-1653)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Joo E, Harada N, Yamane S, Fukushima T, Taura D, Iwasaki K, Sankoda A, Shibue K, Harada T & Suzuki K et al. 2017 Inhibition of gastric inhibitory polypeptide receptor signaling in adipose tissue reduces insulin resistance and hepatic steatosis in high-fat diet-fed mice. Diabetes 66 868879. (https://doi.org/10.2337/db16-0758)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kaelberer MM, Buchanan KL, Klein ME, Barth BB, Montoya MM, Shen X & Bohórquez DV 2018 A gut-brain neural circuit for nutrient sensory transduction. Science 361 eaat5236. (https://doi.org/10.1126/science.aat5236)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kanemaru Y, Harada N, Shimazu-Kuwahara S, Yamane S, Ikeguchi E, Murata Y, Kiyobayashi S, Hatoko T & Inagaki N 2020 Absence of GIP secretion alleviates age-related obesity and insulin resistance. Journal of Endocrinology 245 1320. (https://doi.org/10.1530/JOE-19-0477)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kuhre RE, Gribble FM, Hartmann B, Reimann F, Windeløv JA, Rehfeld JF & Holst JJ 2014 Fructose stimulates GLP-1 but not GIP secretion in mice, rats, and humans. American Journal of Physiology: Gastrointestinal and Liver Physiology 306 G622G 630. (https://doi.org/10.1152/ajpgi.00372.2013)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liou AP, Lu X, Sei Y, Zhao X, Pechhold S, Carrero RJ, Raybould HE & Wank S 2011a The G-protein-coupled receptor GPR40 directly mediates long-chain fatty acid-induced secretion of cholecystokinin. Gastroenterology 140 9039 12. (https://doi.org/10.1053/j.gastro.2010.10.012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Liou AP, Sei Y, Zhao X, Feng J, Lu X, Thomas C, Pechhold S, Raybould HE & Wank SA 2011b The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells. American Journal of Physiology: Gastrointestinal and Liver Physiology 300 G538G 546. (https://doi.org/10.1152/ajpgi.00342.2010)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lo CM, Obici S, Dong HH, Haas M, Lou D, Kim DH, Liu M, D’Alessio D, Woods SC & Tso P 2011 Impaired insulin secretion and enhanced insulin sensitivity in cholecystokinin-deficient mice. Diabetes 60 20002007. (https://doi.org/10.2337/db10-0789)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Lu VB, Gribble FM & Reimann F 2018 Free fatty acid receptors in enteroendocrine cells. Endocrinology 159 28262835. (https://doi.org/10.1210/en.2018-00261)

  • Mace OJ, Schindler M & Patel S 2012 The regulation of K- and L-cell activity by GLUT2 and the calcium-sensing receptor CasR in rat small intestine. Journal of Physiology 590 29172936. (https://doi.org/10.1113/jphysiol.2011.223800)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Madisen L, Zwingman TA, Sunkin SM, Oh SW, Zariwala HA, Gu H, Ng LL, Palmiter RD, Hawrylycz MJ & Jones AR et al. 2010 A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nature Neuroscience 13 133140. (https://doi.org/10.1038/nn.2467)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Meyer-Gerspach AC, Steinert RE, Keller S, Malarski A, Schulte FH & Beglinger C 2013 Effects of chenodeoxycholic acid on the secretion of gut peptides and fibroblast growth factors in healthy humans. Journal of Clinical Endocrinology and Metabolism 98 33513358. (https://doi.org/10.1210/jc.2012-4109)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K & Matsukura S 2001 A role for ghrelin in the central regulation of feeding. Nature 409 194198. (https://doi.org/10.1038/35051587)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Nasteska D, Harada N, Suzuki K, Yamane S, Hamasaki A, Joo E, Iwasaki K, Shibue K, Harada T & Inagaki N 2014 Chronic reduction of GIP secretion alleviates obesity and insulin resistance under high-fat diet conditions. Diabetes 63 23322343. (https://doi.org/10.2337/db13-1563)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Otsuki M, Akiyama T, Shirohara H, Nakano S, Furumi K & Tachibana I 1995 Loss of sensitivity to cholecystokinin stimulation of isolated pancreatic acini from genetically diabetic rats. American Journal of Physiology 268 E531E536. (https://doi.org/10.1152/ajpendo.1995.268.3.E531)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Parker HE, Habib AM, Rogers GJ, Gribble FM & Reimann F 2009 Nutrient-dependent secretion of glucose-dependent insulinotropic polypeptide from primary murine K cells. Diabetologia 52 289298. (https://doi.org/10.1007/s00125-008-1202-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Pilichiewicz AN, Chaikomin R, Brennan IM, Wishart JM, Rayner CK, Jones KL, Smout AJ, Horowitz M & Feinle-Bisset C 2007 Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. American Journal of Physiology: Endocrinology and Metabolism 293 E743E753. (https://doi.org/10.1152/ajpendo.00159.2007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Poreba MA, Dong CX, Li SK, Stahl A, Miner JH & Brubaker PL 2012 Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like peptide-1 secretion from murine intestinal L cells. American Journal of Physiology: Endocrinology and Metabolism 303 E899E907. (https://doi.org/10.1152/ajpendo.00116.2012)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Rehfeld JF 2004 Clinical endocrinology and metabolism. Cholecystokinin. Best Practice and Research: Clinical Endocrinology and Metabolism 18 569586. (https://doi.org/10.1016/j.beem.2004.07.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reimann F, Habib AM, Tolhurst G, Parker HE, Rogers GJ & Gribble FM 2008 Glucose sensing in L cells: a primary cell study. Cell Metabolism 8 532539. (https://doi.org/10.1016/j.cmet.2008.11.002)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sankoda A, Harada N, Iwasaki K, Yamane S, Murata Y, Shibue K, Thewjitcharoen Y, Suzuki K, Harada T & Kanemaru Y et al. 2017 Long-chain free fatty acid receptor GPR120 mediates oil-induced GIP secretion through CCK in male mice. Endocrinology 158 11721180. (https://doi.org/10.1210/en.2017-00090)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sankoda A, Harada N, Kato T, Ikeguchi E, Iwasaki K, Yamane S, Murata Y, Hirasawa A & Inagaki N 2019 Free fatty acid receptors, G protein-coupled receptor 120 and G protein-coupled receptor 40, are essential for oil-induced gastric inhibitory polypeptide secretion. Journal of Diabetes Investigation 10 14301437. (https://doi.org/10.1111/jdi.13059)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Shimazu-Kuwahara S, Harada N, Yamane S, Joo E, Sankoda A, Kieffer TJ & Inagaki N 2017 Attenuated secretion of glucose-dependent insulinotropic polypeptide (GIP) does not alleviate hyperphagic obesity and insulin resistance in ob/ob mice. Molecular Metabolism 6 288294. (https://doi.org/10.1016/j.molmet.2017.01.006)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sundaresan S, Shahid R, Riehl TE, Chandra R, Nassir F, Stenson WF, Liddle RA & Abumrad NA 2013 CD36-dependent signaling mediates fatty acid-induced gut release of secretin and cholecystokinin. FASEB Journal 27 11911202. (https://doi.org/10.1096/fj.12-217703)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Suzuki K, Harada N, Yamane S, Nakamura Y, Sasaki K, Nasteska D, Joo E, Shibue K, Harada T & Hamasaki A et al. 2013 Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity. Journal of Biological Chemistry 288 19291938. (https://doi.org/10.1074/jbc.M112.423137)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sykaras AG, Demenis C, Case RM, McLaughlin JT & Smith CP 2012 Duodenal enteroendocrine I-cells contain mRNA transcripts encoding key endocannabinoid and fatty acid receptors. PLoS ONE 7 e42373. (https://doi.org/10.1371/journal.pone.0042373)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tachibana I, Akiyama T, Kanagawa K, Shiohara H, Furumi K, Watanabe N & Otsuki M 1996 Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats. American Journal of Physiology 270 G730G 737. (https://doi.org/10.1152/ajpgi.1996.270.4.G730)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Tanaka T, Katsuma S, Adachi T, Koshimizu TA, Hirasawa A & Tsujimoto G 2008 Free fatty acids induce cholecystokinin secretion through GPR120. Naunyn-Schmiedeberg’s Archives of Pharmacology 377 523527. (https://doi.org/10.1007/s00210-007-0200-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K, Kvitsiani D, Fu Y, Lu J & Lin Y et al. 2011 A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 71 9951013. (https://doi.org/10.1016/j.neuron.2011.07.026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Whited KL, Thao D, Kent Lloyd KC, Kopin AS & Raybould HE 2006 Targeted disruption of the murine CCK1 receptor gene reduces intestinal lipid-induced feedback inhibition of gastric function. American Journal of Physiology: Gastrointestinal and Liver Physiology 291 G156G 162. (https://doi.org/10.1152/ajpgi.00569.2005)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Wuensch T, Schulz S, Ullrich S, Lill N, Stelzl T, Rubio-Aliaga I, Loh G, Chamaillard M, Haller D & Daniel H 2013 The peptide transporter PEPT1 is expressed in distal colon in rodents and humans and contributes to water absorption. American Journal of Physiology: Gastrointestinal and Liver Physiology 305 G66G 73. (https://doi.org/10.1152/ajpgi.00491.2012)

    • PubMed
    • Search Google Scholar
    • Export Citation