Keywords
obestatin
pancreas
physiology
interaction
How to Cite
Abstract
This paper will briefly describe two hormones affecting the physiological functioning of the pancreas. Obestatin and ghrelin are peptides with antagonistic effects on glucose homeostasis in the body. As is well known, glucose metabolism disorders are at the root of many diseases. One of the best known are diabetes type II and obesity, which are currently a global problem. Moreover, the excess of adipose tissue may lead to consequences such as neoplasm within the gastrointestinal tract[1]. The role of obestatin and ghrelin therefore seems highly important. The knowledge gained in this area can be used to find therapeutic or preventive solutions.
References
Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003 Apr 24;348(17):1625-38.
Shahid Z, Singh G. Physiology, Islets of Langerhans. [Updated 2019 May 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK542302/
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is growth-hormone-releasing acylated peptide from stomach, Nature. 1999; 402(6762): 656-60
Nikolopoulos D , Theocharis S, Kouraklis G. Ghrelin: a potential therapeutic target for cancer. Regul Pept. 2010 Aug 9;163(1-3):7-17. doi: 10.1016/j.regpep.2010.03.011
Castaneda TR, Tong J, Datta R, Culler M, Tschöp MH. Ghrelin In the regulation of body weight and metabolism. Frontiers in Neuroendocrinol. 2010; 31: 44–60
Polińska B, Matowicka-Karna J, Kemona H. The role of ghrelin in the organism. Postepy Hig Med Dosw (online). 2011; 65: 1-7
Hosoda H, Kojima M, Matsuo H, Kangawa K. Purification and characterization of ratdes Gln14-ghrelin, a second endogenous ligand for the growth hormone secretaagogue receptor. The Journal of Biological Chemistry. 2000; 275(29): 21995–22000
Portelli J, Coppens J, Demuyser T, Smolders I. Neuropeptides. Des-acyl ghrelin attenuates pilocarpine-induced limbic seizures via the ghrelin receptor and not the orexin pathway. 2015 Jun;51:1-7. doi: 10.1016/j.npep.2015.04.004. Epub 2015 May 8.
Nonaka M, Kurebayashi N, Murayama T, Sugihara M, Terawaki K, Shiraishi S i in. Therapeutic potential of ghrelin and des-acyl ghrelin against chemotherapy-induced cardiotoxicity. Endocr J. 2017; 64(Suppl.):S35-S39. doi: 10.1507/endocrj.64.S35.
Jaszczyńska-Nowinka K, Markowska A. Rola ghreliny i obestatyny w procesach metabolicznych i nowotworowych u ludzi. Curr. Gynecol. Oncol. 2010; 8 (2), p. 131-138
Chow KBS, Sun J, Man Chu K, Tai Cheung W, Cheng CHK., Wise H. The truncated ghrelin receptor polypeptide (GHS-R1b) is localized in the endoplasmic reticulum where it forms heterodimers with ghrelin receptors (GHS-R1a) to attenuate their cell surface expression Molecular and Cellular Endocrinology. 2012; 348 (1), pp. 247-254. doi.org/10.1016/j.mce.2011.08.034
Cummings D.E. Ghrelin and the short-time- and long-term regulation of appetite and body weight. Physiology & Behavior. 2006; 89(1): 71–84
Adams CE, Greenway FL, Brantley PJ. Lifestyle factors and ghrelin: critical review and implications for weight loss maintenance. Obesity Management. 2010; 10.1111
Michalski B., Krzemińska-Pakuła M., Kasprzak J.D. The way to the heart is through the stomach – the role of ghrelin in pathogenesis of cardiovascular disease, Kardiologia Polska. 2008; 66(5): 564-568
Drott CJ, Franzén P, Carlsson PO. Ghrelin in rat pancreatic islets decreases islet blood flow. Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):139-146. doi: 10.1152/ajpendo.00004.2019.
Sakata N, Yoshimatsu G, Kodama S. Development and Characteristics of Pancreatic Epsilon Cells. Int J Mol Sci. 2019;20(8):1867. Published 2019 Apr 16. doi:10.3390/ijms20081867
Wierup N, Sundler C. Circulating ghrelin levels in human fetuses. Eur J Endocrinol. 2004; 150 (3): 405
Zhang J, Xie T. Ghrelin inhibits cisplatin-induced MDA-MB-231 breast cancer cell apoptosis via PI3K/Akt/mTOR signaling. Exp Ther Med. 2020 Mar;19(3):1633-1640. doi: 10.3892/etm.2019.8398.
Poher AL, Tschöp MH, Müller TD. Ghrelin regulation of glucose metabolism. Peptides. 2018 Feb;100:236-242. doi: 10.1016/j.peptides.2017.12.015.
Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J i in. Ghrelin. Mol Metab. 2015 Mar 21;4(6):437-60. doi: 10.1016/j.molmet.2015.03.005. eCollection 2015 Jun.
Perboni S, Inui A. Appetite and gastrointestinal motility: Role of ghrelin-family peptides. Clin. Nutr. 2010; 29(2): 227–234
Chen CY, Inui A, Asakawa A, Fujino K, Kato I, Chen CC i in. Des-acyl ghrelin acts by CRF type 2 receptors to disrupt fasted stomach motility in conscious rats. Gastroenterology. 2005 Jul;129(1):8-25
Granata R, Settanni F, Julien M, Nano R, Togliatto G, Trombetta A i in. Des-acyl ghrelin fragments and analogues promote survival of pancreatic β-cells and human pancreatic islets and prevent diabetes in streptozotocin-treated rats. J. Med. Chem. 2012; 55 : 2585–2596.
Granata R., Settanni F., Trovato L., Destefanis S., Gallo D, Martinetti M i in. Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic beta-cells. J Endocrinol Invest. 2006 Oct;29(9):RC19-22.
Granata R., Settanni F., Biancone L., Trovato L., Nano R., Bertuzzi F i in. Acylated and unacylated ghrelin promote proliferation and inhibit apoptosis of pancreatic beta-cells and human islets: involvement of 3',5'-cyclic adenosine monophosphate/protein kinase A, extracellular signal-regulated kinase 1/2, and phosphatidyl inositol 3-Kinase/Akt signaling. Endocrinology. 2007 Feb;148(2):512-29. Epub 2006 Oct 26.
Irako T, Akamizu T, Hosoda H, Iwakura H, Ariyasu H, Tojo K i in. Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats. Diabetologia. 2006; 491264–1273. doi:10.1007/s00125-006-0226-3.
Granata R, Baragli A, Settanni F, Scarlatti F, Ghigo E. Unraveling the role of the ghrelin gene peptides in the endocrine pancreas. J Mol Endocrinol. 2010 Sep;45(3):107-18. doi: 10.1677/JME-10-0019. Epub 2010 Jul 1.
Gauna C, Delhanty PJ, van Aken MO, Janssen JA, Themmen AP, Hofland LJ i in. Unacylated ghrelin is active on the INS-1E rat insulinoma cell line independently of the growth hormone secretagogue receptor type 1a and the corticotropin releasing factor 2 receptor. Molecular and Cellular Endocrinology. 2006; 251103–111. doi:10.1016/j.mce.2006.03.040.
Qader SS, Håkanson R, Rehfeld JF, Lundquist I, Salehi A. Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: A study on isolated islets from mouse and rat pancreas. Regulatory Peptides. 2008; 146:230–237
Alamri BN, Shin K, Chappe V, Anini Y. The role of ghrelin in the regulation of glucose homeostasis. Horm Mol Biol Clin Investig. 2016 Apr 1;26(1):3-11. doi: 10.1515/hmbci-2016-0018.
Broglio F, Arvat E, Benso A i in. Grelin, the stomach's natural secretory of growth hormone, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab. 2001; 86 (10): 5083 - 5083, 5086
Napolitano T, Silvano S, Vieira A, Balaji S, Garrido-Utrilla A, Friano ME i in. Role of ghrelin in pancreatic development and function. Diabetes, Obes. Metab. 2018; 20 (Supl. 2): 3–10. doi: 10.1111 / dom.13385.
Broglio F, Gottero C, Prodam F, Gauna C, Muccioli G, Papotti M i in. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab. 2004 Jun;89(6):3062-5.
Zhang JV, Ren PG, Avsian-Kretchmer O, Luo CW, Rauch R, Klein C i in. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science. 2005 Nov 11;310(5750):996-999
Volante M, Roses R, Ceppi P, Rapa I, Cassoni P, Wiedenmann B i in. Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth. J Pathol. 2009 Aug;218(4):458-66. doi: 10.1002/path.2551.
Gronberg M, Tsolakis AV, Magnusson L, Janson ET, Saras J. (2008) Distribution of obestatin and ghrelin in human tissues: immunoreactive cells in the gastrointestinal tract, pancreas, and mammary glands. Journal of Histochemistry and Cytochemistry 56(9): 793-801
Słupecka M, Woliński, Herman AP, Ochniewicz P, Kornacka MK. Biological role of obestatin in physiology and pathophysiology, Medycyna Wieku Rozwojowego. 2012; 16(1):47-52
Seim I, Collet C, Herington AC. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics. 2007; 8: 298
Egerod KL, Holst B, Petersen PS, et al. GPR39 splice variants versus antisense gene LYPD1: expression and regulation in gastrointestinal tract, endocrine pancreas, liver, and white adipose tissue. Mol. Endocrinol., 2007, 21, 1685-1698
Pan W, Tu H, Kastin AJ. Differential BBB interactions of three ingestive peptides: obestatin, ghrelin, and adiponectin. Peptides. 2006; 27(4):911-916
Zhao CM, Furnes MW, Stenström B, Kulseng B, Chen D. Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study. Cell Tissue Res. 2008 Mar;331(3):575-87. Epub 2007 Dec 11.
Ceranowicz P, Warzecha Z, Dembinski A, Cieszkowski J, Dembinski M, Sendur R i in. Pretreatment with obestatin inhibits the development of cerulein‐induced pancreatitis. J. Physiol. Pharmacol. 2009; 60, 95– 101.
Granata R, Settanni F, Gallo D, Trovato L, Biancone L, Cantaluppi V i in. Obestatin promotes survival of pancreatic beta-cells and human islets and induces expression of genes involved in the regulation of beta-cell mass and function. Diabetes. 2008 Apr;57(4):967-79. Epub 2007 Dec 27.
Donath MY, Halban PA. Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia. 2004 Mar;47(3):581-589. doi: 10.1007/s00125-004-1336-4. Epub 2004 Feb 7.
Gesmundo I, Gallo D, Favaro E, Ghigo E, Granata R. Obestatin: a new metabolic player in the pancreas and white adipose tissue. IUBMB Life. 2013 Dec;65(12):976-82. doi: 10.1002/iub.1226. Epub 2013 Nov 12.
Ren AJ, Guo ZF, Wang YK, Wang LG, Wang WZ, Lin L i in. Inhibitory effect of obestatin on glucose-induced insulin secretion in rats. Biochem Biophys Res Commun. 2008 May 9;369(3):969-72. doi: 10.1016/j.bbrc.2008.02.146. Epub 2008 Mar 7.
Granata R, Gallo D, Luque RM, Baragli A, Scarlatti F, Grande C i in. Obestatin regulates adipocyte function and protects against diet‐induced insulin resistance and inflammation. FASEB J. 2012 Aug;26(8):3393-411. doi: 10.1096/fj.11-201343. Epub 2012 May 17.
Egido EM, Hernández R, Marco J, Silvestre RA. Effect of obestatin on insulin, glucagon and somatostatin secretion in the perfused rat pancreas. Regul Pept. 2009 Jan 8;152(1-3):61-6. doi: 10.1016/j.regpep.2008.08.003. Epub 2008 Aug 19
Green BD, Irwin N, Flatt PR. Direct and indirect effects of obestatin peptides on food intake and the regulation of glucose homeostasis and insulin secretion in mice. Peptides. 2007 May;28(5):981-7. Epub 2007 Feb 12
Kiewiet RM, Gauna C, van Aken MO, van de Zande B, van der Lely AJ. Bolus administration of obestatin does not change glucose and insulin levels neither in the systemic nor in the portal circulation of the rat. Peptides. 2008 Dec;29(12):2144-9. doi: 10.1016/j.peptides.2008.09.011. Epub 2008 Sep 26.