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2010 | 59 | 3-4 | 305-314
Article title

Oreksyny w regulacji homeostazy energetycznej

Title variants
Orexin and energy homeostasis regulation
Languages of publication
The neuropeptide orexin stimulates food intake and energy expenditure by acting on two different receptors isoforms OXR1 and OXR2. Orexin exists in two isoforms, both of which bind to OXR1 and OXR2. Studies on genetic engineered animals, which lack or overexpress orexins or its cognate receptors revealed that orexin may play a role in controlling glucose homeostasis and body weight changes. Observational studies in narcoleptic humans, who display orexin deficiency, also indicate that orexin plays a role in in the pathophysiology of type 2 diabetes mellitus and obesity. The results implicate that orexin may become an interesting therapeutic tool in alleviating metabolic diseases and in controlling body weight. Indeed, application of exogenous orexin in narcoleptic humans alleviates the symptoms associated with the disease. Therefore it is important to broaden our understating about the physiological role of orexin as well as to further evaluate its potential in the context of pathophysiology of metabolic diseases. Our review focuses on the recent discoveries of orexin's role in regulating endocrine and metabolic functions in vivo and in vitro In addition, it summarizes the accumulated knowledge about its possible involvement in the pathophysiology of two endemic metabolic diseases - type 2 diabetes mellitus and obesity.
Physical description
  • Katedra Fizjologii i Biochemii Zwierząt, Uniwersytet Przyrodniczy w Poznaniu, Wołyńska 35, 60-637 Poznań, Polska
  • Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Interdisziplinäres Stoffwechsel-Centrum: Endokrinologie, Diabetes und Stoffwechsel, Charite Universitätsmedizin Berlin, 13353 Berlin, Germany
  • Katedra Fizjologii i Biochemii Zwierząt, Uniwersytet Przyrodniczy w Poznaniu, Wołyńska 35, 60-637 Poznań, Polska
  • Adam J. A., Menheere P. P., Van Dielen F. M., Soeters P. B., Buurman W. A., Greve J. W., 2002. Decreased plasma orexin-A levels in obese individuals. Int. J. Obes. Relat. Metab. Disord. 26, 274-276.
  • Adeghate E., Fernandez-Cabezudo M., Hameed R., El-Hasasna H., El Wasila M., Abbas T., Al-Ramadi B., 2010. Orexin-1 receptor co-localizes with pancreatic hormones in islet cells and modulates the outcome of streptozotocin-induced diabetes mellitus. PLoS One 5, e8587.
  • Ammoun S., Johansson L., Ekholm M. E., Holmqvist T., Danis A. S., Korhonen L., Sergeeva O. A., Haas H. L., Akerman K. E., Kukkonen J. P., 2006. OX1 orexin receptors activate extracellular signal-regulated kinase in Chinese hamster ovary cells via multiple mechanisms: the role of Ca2+ influx in OX1 receptor signaling. Mol. Endocrinol. 20, 80-99.
  • Bardos J. I., Ashcroft M., 2005. Negative and positive regulation of HIF-1: a complex network. Biochim. Biophys. Acta. 1755, 107-120.
  • Berezinska M., Zawilska J. B., 2007. Hipokretyny - rola w regulacji rytmu sen-czuwanie i patogenezie narkolepsji. Postępy Hig. Med. Dośw. 61, 1-12.
  • Beuckmann C. T., Yanagisawa M., 2002. Orexins: from neuropeptides to energy homeostasis and sleep/wake regulation. J. Mol. Med. 80, 329-342.
  • Colombo M., Gregersen S., Xiao J., Hermansen K., 2003. Effects of ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets. Pancreas 27, 161-166.
  • De Lecea L., Kilduff T. S., Peyron C., Gao X., Foye P. E., Danielson P. E., Fukuhara C., Battenberg E. L., Gautvik V. T., Bartlett F. S. 2Nd, Frankel W. N., Van Den Pol A. N., Bloom F. E., Gautvik K. M., Sutcliffe J. G., 1998. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. USA 95, 322-327.
  • Digby J. E., Chen J., Tang J. Y., Lehnert H., Matthews R. N., Randeva H. S., 2006. Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B. J. Endocrinol. 191, 129-136.
  • Ducroc R., Voisin T., El Firar A., Laburthe M., 2007. Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways. Diabetes 56, 2494-2500.
  • Funato H., Tsai A. L., Willie J. T., Kisanuki Y., Williams S. C., Sakurai T., Yanagisawa M., 2009. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 9, 64-76.
  • Gerozissis K., 2008. Brain insulin, energy and glucose homeostasis; genes, environment and metabolic pathologies. Eur. J. Pharmacol. 585, 38-49.
  • Goncz E., Strowski M. Z., Grotzinger C., Nowak K. W., Kaczmarek P., Sassek M., Mergler S., El-Zayat B. F., Theodoropoulou M., Stalla G. K., Wiedenmann B., Plockinger U., 2008. Orexin-A inhibits glucagon secretion and gene expression through a Foxo1-dependent pathway. Endocrinology 149, 1618-1626.
  • Hara J., Yanagisawa M., Sakurai T., 2005. Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions. Neurosci Lett. 380, 239-242.
  • Heinonen M. V., Purhonen A. K., Makela K. A., Herzig K. H., 2008. Functions of orexins in peripheral tissues. Acta Physiol. (Oxf.) 192, 471-485.
  • Kirchgessner A. L., Liu M., 1999. Orexin synthesis and response in the gut. Neuron 24, 941-951.
  • Korczynski W., Ceregrzyn M., Matyjek R., Kato I., Kuwahara A., Wolinski J., Zabielski R., 2006. Central and local (enteric) action of orexins. J. Physiol. Pharmacol. 57 (Suppl. 6), 17-42.
  • Longstreth W. T., Jr., Koepsell T. D., Ton T. G., Hendrickson A. F., Van Belle G. 2007. The epidemiology of narcolepsy. Sleep 30, 13-26.
  • Malendowicz L. K., Tortorella C., Nussdorfer G. G., 1999. Orexins stimulate corticosterone secretion of rat adrenocortical cells, through the activation of the adenylate cyclase-dependent signaling cascade. J. Steroid. Biochem. Mol. Biol. 70, 185-188.
  • Malendowicz L. K., Jedrzejczak N., Belloni A. S., Trejter M., Hochół A., Nussdorfer G. G., 2001. Effects of orexins A and B on the secretory and proliferative activity of immature and regenerating rat adrenal glands. Histol. Histopathol. 16, 713-717.
  • Mazza M., Della Marca G., Paciello N., Mennuni G., Bria P., Mazza S., 2005. Orexin, sleep and appetite regulation: a review. Clin. Ter. 156, 93-96.
  • Nishino S., Kanbayashi T., 2005. Symptomatic narcolepsy, cataplexy and hypersomnia, and their implications in the hypothalamic hypocretin/orexin system. Sleep Med. Rev. 9, 269-310.
  • Nowak K. W., Maćkowiak, P., Świtońska, M. M., Fabiś, M., Malendowicz, L. K., 2000. Acute orexin effects on insulin secretion in the rat: In vivo and in vitro studies. Life Sci. 66, 449-454.
  • Nowak K. W., Strowski M. Z., Switonska M. M., Kaczmarek P., Singh V., Fabis M., Mackowiak P., Nowak M., Malendowicz L. K., 2005. Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes. Int. J. Mol. Med. 15, 969-972.
  • Nunez A., Rodrigo-Angulo M. L., Andres I. D., Garzon M., 2009. Hypocretin/Orexin neuropeptides: participation in the control of sleep-wakefulness cycle and energy homeostasis. Curr. Neuropharmacol. 7, 50-59.
  • Ouedraogo R., Naslund E., Kirchgessner A. L., 2003. Glucose regulates the release of orexin-a from the endocrine pancreas. Diabetes 52, 111-117.
  • Ramanjaneya M., Conner A. C., Chen J., Kumar P., Brown J. E., Johren O., Lehnert H., Stanfield P. R., Randeva H. S., 2009. Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B. J. Endocrinol. 202, 249-261.
  • Rodgers R. J., Ishii Y., Halford J. C., Blundell J. E., 2002. Orexins and appetite regulation. Neuropeptides 36, 303-325.
  • Sakurai T., Amemiya A., Ishii M., Matsuzaki I., Chemelli R. M., Tanaka H., Williams S. C., Richardson J. A., Kozlowski G. P., Wilson S., Arch J. R., Buckingham R. E., Haynes A. C., Carr S. A., Annan R. S., Mcnulty D. E., Liu W. S., Terrett J. A., Elshourbagy N. A., Bergsma D. J., Yanagisawa M., 1998. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92, 573-585.
  • Shiuchi T., Haque M. S., Okamoto S., Inoue T., Kageyama H., Lee S., Toda C., Suzuki A., Bachman E. S., Kim Y. B., Sakurai T., Yanagisawa M., Shioda S., Imoto K., Minokoshi Y., 2009. Hypothalamic orexin stimulates feeding-associated glucose utilization in skeletal muscle via sympathetic nervous system. Cell Metab. 10, 466-480.
  • Sikder D., Kodadek T., 2007. The neurohormone orexin stimulates hypoxia-inducible factor-1 activity. Genes. Dev. 21, 2995-3005.
  • Smart D., Jerman J., 2002. The physiology and pharmacology of the orexins. Pharmacol. Ther. 94, 51-61.
  • Sweet D. C., Levine A. S., Billington C. J., Kotz C. M., 1999. Feeding response to central orexins. Brain Res. 821, 535-538.
  • Takano S., Kanai S., Hosoya H., Ohta M., Uematsu H., Miyasaka K., 2004. Orexin-A does not stimulate food intake in old rats. Am. J. Physiol. Gastrointest. Liver Physiol. 287, G1182-1187.
  • Toshinai K., Date Y., Murakami N., Shimada M., Mondal M. S., Shimbara T., Guan J. L., Wang Q. P., Funahashi H., Sakurai T., Shioda S., Matsukura S., Kangawa K., Nakazato M., 2003. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology 144, 1506-1512.
  • Tsuneki H., Sugihara Y., Honda R., Wada T., Sasaoka T., Kimura I., 2002. Reduction of blood glucose level by orexins in fasting normal and streptozotocin-diabetic mice. Eur. J. Pharmacol. 448, 245-252.
  • Tsuneki H., Murata S., Anzawa Y., Soeda Y., Tokai E., Wada T., Kimura I., Yanagisawa M., Sakurai T., Sasaoka T., 2008. Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice. Diabetologia 51, 657-667.
  • Tsuneki H., Wada T., Sasaoka T., 2010. Role of orexin in the regulation of glucose homeostasis. Acta Physiol. (Oxf.) 198, 335-348.
  • Wang J., Osaka T., Inoue S., 2001. Energy expenditure by intracerebroventricular administration of orexin to anesthetized rats. Neurosci. Lett. 315, 49-52.
  • Zwirska-Korczala K., Adamczyk-Sowa M., Sowa P., Pilc K., Suchanek R., Pierzchala K., Namyslowski G., Misiolek M., Sodowski K., Kato I., Kuwahara A., Zabielski R., 2007. Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells proliferation and oxidative metabolism. J. Physiol. Pharmacol. 58 (Suppl. 1), 53-64.
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Publication order reference
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