PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2016 | 25 | 2 |
Tytuł artykułu

Hypothalamo-gastrointestinal axis – role in food intake regulation

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
In homoeothermic vertebrates, one of the most important physiological mechanism concerns the maintenance of the homeostasis. The principal regulator of energy intake is situated in the central nervous system (CNS), where numerous central and peripheral hormones regulate the energy homeostasis. Neuronal pathways between some hypothalamic nuclei create the appetite regulating network in which orexigenic and anorexigenic circuits modify food intake and energy expenditure. In recent years, a serious problem concerning obesity and related diseases emerged in civilized societies. In order to resolve the issues of disturbances of food intake, it is necessary to understand mechanisms guiding neuroendocrine control of metabolic processes. Previous studies have focused on the role of gut peptides (now called gastrointestinal hormones) only in the regulation of the gastrointestinal tract function. Nowadays, it has become clear that gut hormones signalize neural and endocrine mechanisms to the CNS to create the brain-gut axis which regulates energy homeostasis. This review is an attempt to summarize the knowledge about the hypothalamus-gastrointestinal axis. In the first part of the review the hypothalamic ‘centre’, engaged in the body energy homeostasis regulation and being the most important neuropeptide acting in this region, is presented. In the second one, the information about the origin, properties and some endocrine actions of the most important and best studied, in our opinion, gastrointestinal hormones regulating the food intake is reviewed. Detailed knowledge of the regulation of appetite mechanisms should be an opportunity to overcome an increasingly common problem of civilization – the epidemic of obesity
Słowa kluczowe
EN
Wydawca
-
Rocznik
Tom
25
Numer
2
Opis fizyczny
p.97-108,fig.,ref.
Twórcy
  • The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences Instytucka 3, 05-110 Jablonna, Poland
autor
  • The Kielanowski Institute of Animal Physiology and Nutrition Polish Academy of Sciences Instytucka 3, 05-110 Jablonna, Poland
Bibliografia
  • Abbott C.R., Monteiro M., Small C.J., Sajedi A., Smith K.L., Parkinson J.R., Ghatei M.A., Bloom S.R., 2005. The inhibitory effects of peripheral administration of peptide YY3-36 and glucagonlike peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res. 1044, 127–131
  • Adrian T.E., Bloom S.R., Bryant M.G., Polak J.M., Heitz P.H., Barnes A.J., 1976. Distribution and release of human pancreatic polypeptide. Gut 17, 940–944
  • Adrian T.E., Ferri G.L., Bacarese-Hamilton A.J., Fuessl H.S., Polak J.M., Bloom S.R., 1985. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 89, 1070–1077
  • Asakawa A., Inui A., Yuzuriha H., Ueno N., Katsuura G., Fujimiya M., Fujino M.A., Niijima A., Meguid M.M., Kasuga M., 2003. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 124, 1325–1336
  • Ballesta J., Carlei F., Bishop A.E., Steel J.H., Gibson S.J., Fahey M., Hennessey R., Domin J., Bloom S.R., Polak J.M., 1988. Occurrence and developmental pattern of neuromedin U-immunoreactive nerves in the gastrointestinal tract and brain of the rat. Neuroscience 25, 797–816
  • Barrera J.G., Sandoval D.A., D’Alessio D.A., Seeley R.J., 2011. GLP-1 and energy balance: an integrated model of short-term and long-term control. Nat. Rev. Endocrinol. 7, 507–516
  • Batterham R.L., Cohen M.A., Ellis S.M., Le Roux C.W., Withers D.J., Frost G.S., Ghatei M.A., Bloom S.R., 2003a. Inhibition of food intake in obese subjects by peptide YY3-36. N. Engl. J. Med. 349, 941–948
  • Batterham R.L., Heffron H., Kapoor S., Chivers J.E., Chandarana K., Herzog H., Le Roux C.W., Thomas E.L., Bell J.D., Withers D.J., 2006. Critical role for peptide YY in protein-mediated satiation and body-weight regulation. Cell Metab. 4, 223–233
  • Batterham R.L., Le Roux C.W., Cohen M.A., Park A.J., Ellis S.M., Patterson M., Frost G.S., Ghatei M.A., Bloom S.R., 2003b. Pancreatic polypeptide reduces appetite and food intake in humans. J. Clin. Endocrinol. Metab. 88, 3989–3992
  • Benoit S.C., Schwartz M.W., Lachey J.L. et al., 2000. A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J. Neurosci. 20, 3442–3448
  • Bruzzone F., Lectez B., Alexandre D. et al., 2007. Distribution of 26RFa binding sites and GPR103 mRNA in the central nervous system of the rat. J. Comp. Neurol. 503, 573–591
  • Cason A.M., Smith R.J., Tahsili-Fahadan P., Moorman D.E., Sartor G.C., Aston-Jones G., 2010. Role of orexin/hypocretin in reward-seeking and addiction: implications for obesity. Physiol. Behav. 100, 419–428
  • Castañeda T.R., Tong J., Datta R., Culler M., Tschöp M.H., 2010. Ghrelin in the regulation of body weight and metabolism. Front. Neuroendocrinol. 31, 44–60
  • Chartrel N., Alonzeau J., Alexandre D., Jeandel L., Alvear-Perez R., Leprince J., Boutin J., Vaudry H., Anouar Y., Llorens-Cortes C., 2011. The RFamide neuropeptide 26RFa and its role in the control of neuroendocrine functions. Front. Neuroendocrinol. 32, 387–397
  • Chartrel N., Bruzzone F., Leprince J. et al., 2006. Structure and functions of the novel hypothalamic RFamide neuropeptides R-RFa and 26RFa in vertebrates. Peptides 27, 1110–1120
  • Chartrel N., Dujardin C., Anouar Y. et al., 2003. Identification of 26RFa, a hypothalamic neuropeptide of the RFamide peptide family with orexigenic activity. Proc. Nat. Acad. Sci. USA 100, 15247–15252
  • Coll A.P., Farooqi I.S., O’Rahilly S., 2007. The hormonal control of food intake. Cell 129, 251–262
  • Covasa M., Marcuson J.K., Ritter R.C., 2001. Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin. Am. J. Physiol. Regul. Integr. Comp. Physiol. 280, R331–R337
  • Cowley M.A., Smith R.G., Diano S. et al., 2003. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37, 649–661
  • Cummings D.E., Purnell J.Q., Frayo R.S., Schmidova K., Wisse B.E., Weigle D.S., 2001. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50, 1714–1719
  • Cummings D.E., Weigle D.S., Frayo R.S., Breen P.A., Ma M.K., Dellinger E.P., Purnell J.Q., 2002. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N. Engl. J. Med. 346, 1623–1630
  • Dakin C.L., Small C.J., Batterham R.L., Neary N.M., Cohen M.A., Patterson M., Ghatei M.A., Bloom S.R., 2004. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 145, 2687–2695
  • Date Y., Kojima M., Hosoda H., Sawaguchi A., Mondal M.S., Suganuma T., Matsukura S., Kangawa K., Nakazato M., 2000. Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans. Endocrinology 141, 4255–4261
  • Dejgaard T.F., 2015. Efficacy and safety of liraglutide added to insulin in type 1 diabetes: The LIRA-1 trial. 75th Scientific Sessions of the American Diabetes Association (ADA), Session ‘Updates on GLP-1 Agonists’, June 5 - 9, 2015, Boston, MA (USA) http://professional2.diabetes.org/presentations_details.aspx?congress=238
  • Deng H.-W., Deng H., Liu Y.-J. et al., 2002. A genomewide linkage scan for quantitative-trait loci for obesity phenotypes. Am. J. Hum. Genet. 70, 1138–1151
  • Douglass J., McKinzie A.A., Couceyro P., 1995. PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J. Neurosci. 15, 2471–2481
  • Druce M.R., Minnion J.S., Field B.C.T., Patel S.R., Shillito J.C., Tilby M., Beale K.E.L., Murphy K.G., Ghatei M.A., Bloom S.R., 2009. Investigation of structure-activity relationships of oxyntomodulin (Oxm) using Oxm analogs. Endocrinology 150, 1712– 1721
  • Drucker D.J., Nauck M.A., 2006. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet 368, 1696–1705
  • Dun S.L., Brailoiu G.C., Brailoiu E., Yang J., Chang J.K., Dun N.J., 2006. Distribution and biological activity of obestatin in the rat. J. Endocrinol. 191, 481–489
  • Filipek B., 2010. Place of incretin mimetics and dipeptidyl peptidase-4 inhibitors in the treatment of type 2 diabetes. Farm. Pol. 66, 55–61
  • Fuji R., Hosoya M., Fukusumi S., Kawamata Y., Habata Y., Hinuma S., Onda H., Nishimura O., Fujino M., 2000. Identification of neuromedin U as the cognate ligand of the orphan G proteincoupled receptor FM-3. J. Biol. Chem. 275, 21068–21074
  • Germano C.M.R., de Castro M., Rorato R., Laguna M.T.C., AntunesRodrigues J., Elias C.F., Elias L.L.K., 2007. Time course effects of adrenalectomy and food intake on cocaine- and amphetamine-regulated transcript expression in the hypothalamus. Brain Res. 1166, 55–64
  • Gibbs J., Young R.C., Smith G.P., 1973. Cholecystokinin decreases food intake in rats. J. Comp. Physiol. Psychol. 84, 488–495
  • Gibson W., Liu J., Gaylinn B., Thorner M.O., Meneilly G.S., Babich S.L., Thompson D., Chanoine J.P., 2010. Effects of glucose and insulin on acyl ghrelin and desacyl ghrelin, leptin, and adiponectin in pregnant women with diabetes. Metabolism 59, 841–847
  • Goebel M., Stengel A., Wang L., Taché Y., 2011. Central nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing inter-meal intervals. Peptides 32, 36–43
  • Goebel-Stengel M., Wang L., Stengel A., Taché Y., 2011. Localization of nesfatin-1 neurons in the mouse brain and functional implication. Brain Res. 1396, 20–34
  • Graham E.S., Turnbull Y., Fotheringham P., Nilaweera K., Mercer J.G., Morgan P.J., Barrett P., 2003. Neuromedin U and neuromedin U receptor-2 expression in the mouse and rat hypothalamus: effects of nutritional status. J. Neurochem. 87, 1165–1173
  • Granata R., Settanni F., Gallo D. et al., 2008. Obestatin promotes survival of pancreatic β-cell and human islets and induces expression of genes involved in the regulation of β-cell mass and function. Diabetes 57, 967–979
  • Hanada R., Teranishi H., Pearson J.T. et al., 2004. Neuromedin U has a novel anorexigenic effect independent of the leptin signaling pathway. Nature Med. 10, 1067–1073
  • Hankir M.K., Parkinson J.R.C., Minnion J.S., Addison M.L., Bloom S.R., Bell J.D., 2011. Peptide YY3-36 and pancreatic polypeptide differentially regulate hypothalamic neuronal activity in mice in vivo as measured by manganese-enhanced magnetic resonance imaging. J. Neuroendocrinol. 23, 371–380
  • Hewson A.K., Dickson S.L., 2000. Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats. J. Neuroendocrinol. 12, 1047–1049
  • Hosoda H., Kojima M., Mizushima T., Shimizu S., Kangawa K., 2003. Structural divergence of human ghrelin. Identification of multiple ghrelin-derived molecules produced by post-translational processing. J. Biol. Chem. 278, 64–70
  • Howard A.D., Wang R., Pong S.-S. et al., 2000. Identification of receptors for neuromedin U and its role in feeding. Nature 406, 70–74
  • Kampe J., Wiedmer P., Pfluger P.T. et al., 2006. Effect of central administration of QRFP (26) peptide on energy balance and characterization of a second QRFP receptor in rat. Brain Res. 1119, 133–149
  • Kissileff H.R., Pi-Sunyer F.X., Thornton J., Smith G.P., 1981. C-terminal octapeptide of cholecystokinin decreases food intake in man. Am. J. Clin. Nutr. 34, 154–160
  • Koda S., Date Y., Murakami N. et al., 2005. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 146, 2369–2375
  • Kojima M., Hosoda H., Date Y., Nakazato M., Matsuo H., Kangawa K., 1999. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660
  • Kowalski T.J., Spar B.D., Markowitz L. et al., 2005. Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice. J. Endocrinol. 185, 151–164
  • Lagaud G.J., Young A., Acena A., Morton M.F., Barrett T.D., Shankley N.P., 2007. Obestatin reduces food intake and suppresses body weight gain in rodents. Biochem. Biophys. Res. Commun. 357, 264–269
  • Larhammar D., 1996. Structural diversity of receptors for neuropeptide Y, peptide YY and pancreatic polypeptide. Regul. Peptides 65, 165–174
  • Lawrence C.B., Snape A.C., Baudoin F.M.-H., Luckman S.M., 2002. Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology 143, 155–162
  • Le Quellec A., Kervran A., Blache P., Ciurana A.J., Bataille D., 1992. Oxyntomodulin-like immunoreactivity: diurnal profile of a new potential enterogastrone. J. Clin. Endocrinol. Metab. 74, 1405–1409
  • Lectez B., Jeandel L., El-Yamani F.Z. et al., 2009. The orexigenic activity of the hypothalamic neuropeptide 26RFa is mediated by the neuropeptide Y and proopiomelanocortin neurons of the arcuate nucleus. Endocrinology 150, 2342–2350
  • Liddle R.A., Goldfine I.D., Rosen M.S., Taplitz R.A., Williams J.A., 1985. Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J. Clin. Invest. 75, 1144–1152
  • Lin Y., Hall R.A., Kuhar M.J., 2011. CART peptide stimulation of G protein-mediated signaling in differentiated PC12 cells: identification of PACAP 6-38 as a CART receptor antagonist. Neuropeptides 45, 351–358
  • Liu Y.-L., Semjonous N.M., Murphy K.G., Ghatei M.A., Bloom S.R., 2008. The effects of pancreatic polypeptide on locomotor activity and food intake in mice. Int. J. Obesity 32, 1712–1715
  • Lo C.C., Davidson W.S., Hibbard S.K., Georgievsky M., Lee A., Tso P., Woods S.C., 2014. Intraperitoneal CCK and fourth-intraventricular apo AIV require both peripheral and NTS CCK1R to reduce food intake in male rats. Endocrinology 155, 1700–1707
  • Lopaschuk G.D., Ussher J.R., Jaswal J.S., 2010. Targeting intermediary metabolism in the hypothalamus as a mechanism to regulate appetite. Pharmacol. Rev. 62, 237–264
  • Maejima Y., Sedbazar U., Suyama S. et al., 2009. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab. 10, 355–365
  • Mercer A.J., Hentges S.T., Meshul C.K., Low M.J., 2013. Unraveling the central proopiomelanocortin neural circuits. Front. Neurosci. 7, 19
  • Michel M.C., Beck-Sickinger A., Cox H., Doods H.N., Herzog H., Larhammar D., Quirion R., Schwartz T., Westfall T., 1998. XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol. Rev. 50, 143–150
  • Minamino N., Kangawa K., Matsuo H., 1985. Neuromedin U-8 and U-25: novel uterus stimulating and hypertensive peptides identified in porcine spinal cord. Biochem. Biophys. Res. Commun. 130, 1078–1085
  • Mitchell J.D., Maguire J.J., Davenport A.P., 2009. Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S. Brit. J. Pharmacol. 158, 87–103
  • Moran T.H., Baldessarini A.R., Salorio C.F., Lowery T., Schwartz G.J., 1997. Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin. Am. J. Physiol. 272, R1245–R1251
  • Moran T.H., Kinzig K.P., 2004. Gastrointestinal satiety signals II. Cholecystokinin. Am. J. Physiol. Gastrointest. Liver Physiol. 286, G183–G188
  • Moriya R., Sano H., Umeda T., Ito M., Takahashi Y., Matsuda M., Ishihara A., Kanatani A., Iwaasa H., 2006. RFamide peptide QRFP43 causes obesity with hyperphagia and reduced thermogenesis in mice. Endocrinology 147, 2916–2922
  • Muccioli G., Lorenzi T., Lorenzi M., Ghè C., Arnoletti E., Raso G.M., Castellucci M., Gualillo O., Meli R., 2011. Beyond the metabolic role of ghrelin: A new player in the regulation of reproductive function. Peptides 32, 2514–2521
  • Nakazato M., Hanada R., Murakami N., Date Y., Mondal M.S., Kojima M., Yoshimatsu H., Kangawa K., Matsukura S., 2000. Central effects of neuromedin U in the regulation of energy homeostasis. Biochem. Biophys. Res. Commun. 277, 191–194
  • 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, 194–198
  • Nguyen A.D., Mitchell N.F., Lin S. et al., 2012. Y1 and Y5 receptors are both required for the regulation of food intake and energy homeostasis in mice. PLoS ONE 7, e40191, doi:10.1371/ journal.pone.0040191
  • Nonaka N., Shioda S., Niehoff M.L., Banks W.A., 2003. Characterization of blood–brain barrier permeability to PYY3-36 in the mouse. J. Pharmacol. Exp. Ther. 306, 948–953
  • Oh-I S., Shimizu H., Satoh T. et al., 2006. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 443, 709–712
  • Okere B., Xu L., Roubos E.W., Sonetti D., Kozicz T., 2010. Restraint stress alters the secretory activity of neurons co-expressing urocortin- 1, cocaine- and amphetamine-regulated transcript peptide and nesfatin-1 in the mouse Edinger-Westphal nucleus. Brain Res. 1317, 92–99
  • Ozaki Y., Onaka T., Nakazato M., Saito J., Kanemoto K., Matsumoto T., Ueta Y., 2002. Centrally administered neuromedin U activates neurosecretion and induction of c-fos messenger ribonucleic acid in the paraventricular and supraoptic nuclei of rat. Endocrinology 143, 4320–4329
  • Pan W., Tu H., Kastin A.J., 2006. Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin. Peptides 27, 911–916
  • Parker R.M.C., Herzog H., 1999. Regional distribution of Y-receptor subtype mRNAs in rat brain. Eur. J. Neurosci. 11, 1431–1448
  • Peier A.M., Desai K., Hubert J. et al., 2011. Effects of peripherally administered neuromedin U on energy and glucose homeostasis. Endocrinology 152, 2644–2654
  • Raddatz R., Wilson A.E., Artymyshyn R. et al., 2000. Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system. J. Biol. Chem. 275, 32452–32459
  • Reeve J.R. Jr., Eysselein V.E., Ho F.J., Chew P., Vigna S.R., Liddle R.A., Evans C., 1994. Natural and synthetic CCK-58. Novel reagents for studying cholecystokinin physiology. Ann. N. Y. Acad. Sci. 713, 11–21
  • Rehfeld J.F., Bundgaard J.R., Friis-Hansen L., Goetze J.P., 2003. On the tissue-specific processing of procholecystokinin in the brain and gut - a short review. J. Physiol. Pharmacol. 54, 73–79
  • Robson A.J., Rousseau K., Loudon A.S., Ebling F.J., 2002. Cocaine and amphetamine-regulated transcript mRNA regulation in the hypothalamus in lean and obese rodents. J. Neuroendocrinol. 14, 697–709
  • Sakurai T., Amemiya A., Ishii M. et al., 1998. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G proteincoupled receptors that regulate feeding behavior. Cell 92, 573–585
  • Schjoldager B., Mortensen P.E., Myhre J., Christiansen J., Holst J.J., 1989. Oxyntomodulin from distal gut. Role in regulation of gastric and pancreatic functions. Diges. Dis. Sci. 34, 1411–1419
  • Schneeberger M., Gomis R., Claret M., 2014. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J. Endocrinol. 220, T25–T46
  • Scott V., Kimura N., Stark J.A., Luckman S.M., 2005. Intravenous peptide YY3–36 and Y2 receptor antagonism in the rat: effects on feeding behaviour. J. Neuroendocrinol. 17, 452–457
  • Shimizu H., Oh-I S., Hashimoto K. et al., 2009. Peripheral administration of nesfatin-1 reduces food intake in mice: the leptinindependent mechanism. Endocrinology 150, 662–671
  • Takayasu S., Sakurai T., Iwasaki S. et al., 2006. A neuropeptide ligand of the G protein-coupled receptor GPR103 regulates feeding, behavioral arousal, and blood pressure in mice. Proc. Nat. Acad. Sci. USA 103, 7438–7443
  • Tang-Christensen M., Vrang N., Larsen P.J., 2001. Glucagon-like peptide containing pathways in the regulation of feeding behaviour. Int. J. Obes. Relat. Metab. Disord. 25, Suppl. 5, S42–S47
  • Verdich C., Flint A., Gutzwiller J.-P., Näslund E., Beglinger C., Hellström P.M., Long S.J., Morgan L.M., Holst J.J., Astrup A., 2001. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on energy intake in humans. J. Clin. Endocrinol. Metab. 86, 4382–4389
  • Wortley K.E., Chang G.-Q., Davydova Z., Fried S.K., Leibowitz S.F., 2004. Cocaine- and amphetamine-regulated transcript in the arcuate nucleus stimulates lipid metabolism to control body fat accrual on a high-fat diet. Regul. Peptides 117, 89–99
  • Wynne K., Park A.J., Small C.J., Meeran K., Ghatei M.A., Frost G.S., Bloom S.R., 2006. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int. J. Obesity 30, 1729–1736
  • Wynne K., Stanley S., McGowan B., Bloom S., 2005. Appetite control. J. Endocrinol. 184, 291–318
  • Xu M.M., 2015. Tolerability, safety, and pharmacokinetics of once weekly administration of long-acting GLP-1 analogue in healthy subjects. 75th Scientific Sessions of the American Diabetes Association (ADA), Session ‘Updates on GLP-1 Agonists’, June 5 - 9, 2015, Boston, MA (USA) http://professional2. diabetes.org/presentations_details.aspx?congress=238
  • Zhang J.V., Ren P.-G., Avsian-Kretchmer O., Luo C.-W., Rauch R., Klein C., Hsueh A.J.W., 2005. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake. Science 310, 996–999
  • Zigman J.M., Jones J.E., Lee C.E., Saper C.B., Elmquist J.K., 2006. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J. Comp. Neurol. 494, 528–548
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-1e511c5b-6be5-4ada-9ae3-d91bfc1bf1a0
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.