Wikipedia

User:Amymy0731/sandbox

飢餓素（英文：Gherlin）是一種存在於血液循環中，由腸胃道的內分泌細胞所分泌的賀爾蒙，其中又屬胃分泌最多[1][2]。它被稱為飢餓素是因為它能夠增加食物攝取。[2]在餐前飢餓時，飢餓素的血液中濃度最高，進食後濃度降低。[2] [3]飢餓素可能透過增加胃的活動性和胃酸分泌[2]，為身體對食物的攝入做準備。[2][4]

飢餓素能夠活化腦垂體前葉和下視丘弓狀核中的細胞，[2][5]其中包括可引起食慾的神經肽Y神經元。[2][6]飢餓素能夠刺激具有特定受體的大腦結構：飢餓素受體1A（GHSR -1A）。[2][7]飢餓素同時也能夠調節神經結構中的犒賞系統[8]、學習和記憶，睡眠-甦醒週期、味覺、犒賞行為和葡萄糖代謝。[2][9][10]

歷史與命名 edit

飢餓素的首次發現是在1999年[2]發現了飢餓素受體（稱為生長激素促分泌素受體1A或GHS-R）之後。其命名是以它能夠促生長激素分泌的功能來命名，源自於原始印歐語中的gʰre，意謂成長。[2]

基因、轉錄產物與構造 edit

File:由 own work - adapted from http://www.pdb.org/pdb/files/1p7x.pdb using PyMOL, 公有領域, https://commons.wikimedia.org/w/index.php?curid=4790168
Ghrelin

其GHRL基因產生的mRNA有四個外顯子，並產生五種產物：第一種是117個氨基酸的前飢餓素原。（與促胃動素原同源；兩者都是促胃動素家族的成員）。將前飢餓素原剪接後產生飢餓素原，再剪接後產生一個具有28個氨基酸的未醯化飢餓素和一個醯化飢餓素（C-Gherlin）。據推測，肥胖抑制素可能從C-ghrelin剪接而成。[11]

飢餓素只有在飢餓素醯基轉移酶（GOAT）的幫助下，結構中的辛酸在轉譯後與絲氨酸的3號位連接時才具有活性。它位於胃和胰臟中的飢餓素細胞的細胞膜上[12]，而未辛醯化的形式則稱為去醯基飢餓素，其無法活化GHS-R受體，但具有其他作用：心臟方面的功能[13]、刺激食慾[14]和抑制肝臟輸出葡萄糖[15]。同時也觀察到，辛醯基以外的側鏈也可以觸發飢餓素受體[16]。 特別的是，已發現癸醯飢餓素在小鼠循環中的飢餓素站了一定比例，但截至2011年，其在人體中的存在尚未確定。[17]

飢餓素細胞 edit

別名 edit

飢餓素細胞也被稱為胰臟的A-like cell、X-cell（X意謂功能不明）、小鼠中的X/A-like cell、胰臟中的ε細胞、人體的P/D sub 1 cell、或Gr cell（Gherlin的簡稱）[18]。

位置 edit

飢餓素細胞主要存在於胃[19]和十二指腸中，但也存在於空腸、肺、胰島[20]、性腺、腎上腺皮質、胎盤和腎臟中。最近也有研究顯示，飢餓素能夠在大腦局部產生[21]。

特色 edit

飢餓素細胞存在於胃底腺細胞中（佔細胞的20％）[22]、幽門和小腸中，是卵圓形的顆粒性細胞[23]，同時具有胃泌素受體[24]，且有一些能夠產生脂肪激素nesfatin-1[25]。飢餓素細胞在胰臟中沒有終末分化的步驟，它們作為前驅細胞，可以產生A細胞、PP細胞和β細胞。[26]

血液中濃度 edit

飢餓素在血液中的濃度在pmol / l的範圍內。具有活性的飢餓素含量和總飢餓素含量都可以被測量出來[27] 。循環中的飢餓素濃度在進食前升高，並在進食後下降[28]，並且對於蛋白質和碳水化合物的反應比對脂質的反應更強烈。[17]

飢餓素受體 edit

飢餓素受體GHS-R1A（由生長激素促分泌素受體剪接而來）可以調節多項飢餓素造成的生物效應，包括：刺激生長激素的釋放、增加飢餓感、調節葡萄糖和脂質的代謝、調節腸胃蠕動和分泌、保護神經和心血管細胞以及調節免疫功能。[29]它們大量存在於下視丘和腦垂體、迷走神經上（在傳入的細胞體和傳出的神經末梢上）以及整個胃腸道中。[12] [38]

作用地點 edit

葡萄糖代謝 edit

整個飢餓素系統（包含dAG、AG、GHS-R、GOAT）皆具有調節葡萄糖的作用。[30]

睡眠 edit

初步研究表明，飢餓素參與了晝夜規律的調節[2]。雖然有文獻表示，沒有發現有力的證據顯示限制睡眠會影響飢餓素以及瘦素的濃度或能量消耗。[31]

生殖系統 edit

飢餓素對促性腺激素釋放激素（GnRH）的分泌具有抑制作用，可能導致生育力下降。[32]

胎兒和新生兒 edit

飢餓素在胎兒時期的早期肺臟產生，並具有促進肺生長的功能。[33] 臍帶血中飢餓素的濃度也顯示，飢餓素濃度和新生兒出生體重之間的相關性。[27]

厭食症和肥胖 edit

肥胖個體血漿中的飢餓素濃度低於瘦型個體[2] [34]，由此顯示，飢餓素並不直接造成肥胖，只有在小胖威利症候群引起的肥胖中，高濃度的飢餓素能夠造成食物攝入量的增加[35][36]。與體重過輕和正常體重的兩個對照組相比，神經性厭食症的血漿飢餓素濃度更高[37][38][39]。體型較為削瘦的人在一天中，從午夜到黎明的這段時間的飢餓素濃度較高，這顯示肥胖者的晝夜規律系統存在缺陷[40]。同時，癌症引起的惡體質患者也有高濃度的飢餓素[41]。尚無足夠的證據得出支持或反對使用生長素釋放肽治療癌症相關惡病質的結論[42]。

相關疾病的控管與治療 edit

胃繞道手術 edit

與體型瘦削和節食減肥的人相比，進行胃繞道手術的人不僅減少了腸道容量，甚至能夠降低體內飢餓素濃度。[2][43]在此方面，尚未有研究闡明，接受胃繞道手術的人，體內的飢餓素濃度是否在減輕的體重穩定下來後就恢復正常濃度。[44]統計也顯示，胃繞道的相關手術中，進行袖狀胃切除術的人從長遠來看，體內飢餓素濃度能夠降低約60％。[45]

相關資料 edit

●下視丘-腦垂體-生長軸 ●生長激素促分泌素清單

參考資料 edit

  1. ^ Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K (December 1999). "Ghrelin is a growth-hormone-releasing acylated peptide from stomach". Nature. 402 (6762): 656–60. Bibcode:1999Natur.402..656K. doi:10.1038/45230. PMID 10604470.
  2. ^ a b c d e f g h i j k l m n Müller TD, Nogueiras R, Andermann ML, Andrews ZB, Anker SD, Argente J, et al. (June 2015). "Ghrelin". Molecular Metabolism. 4 (6): 437–60. doi:10.1016/j.molmet.2015.03.005. PMC 4443295. PMID 26042199.
  3. ^ Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS (August 2001). "A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans". Diabetes. 50 (8): 1714–9. doi:10.2337/diabetes.50.8.1714. PMID 11473029.
  4. ^ Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG (April 2000). "Central nervous system control of food intake". Nature. 404 (6778): 661–71. doi:10.1038/35007534. PMID 10766253.
  5. ^ Dickson SL, Leng G, Robinson IC (March 1993). "Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons". Neuroscience. 53 (2): 303–6. doi:10.1016/0306-4522(93)90197-n. PMID 8492908.
  6. ^ Dickson SL, Luckman SM (February 1997). "Induction of c-fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6". Endocrinology. 138 (2): 771–7. doi:10.1210/endo.138.2.4907. PMID 9003014.
  7. ^ Howard AD, Feighner SD, Cully DF, Arena JP, Liberator PA, Rosenblum CI, et al. (August 1996). "A receptor in pituitary and hypothalamus that functions in growth hormone release". Science. 273 (5277): 974–7. Bibcode:1996Sci...273..974H. doi:10.1126/science.273.5277.974. PMID 8688086.
  8. ^ Nestler EJ, Hyman SE, Holtzman DM, Malenka RC (2015). "Neural and Neuroendocrine Control of the Internal Milieu". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3rd ed.). New York: McGraw-Hill Medical. pp. 245–267. ISBN 9780071827690.
  9. ^ Dickson SL, Egecioglu E, Landgren S, Skibicka KP, Engel JA, Jerlhag E (June 2011). "The role of the central ghrelin system in reward from food and chemical drugs". Molecular and Cellular Endocrinology. 340 (1): 80–7. doi:10.1016/j.mce.2011.02.017. hdl:2077/26318. PMID 21354264.
  10. ^ Le Moal M (2002). "Mesocorticolimbic Dopaminergic Neurons". In Davis KL, Charney D, Coyle JT, Nemeroff C (eds.). Neuropsychopharmacology : the fifth generation of progress : an official publication of the American College of Neuropsychopharmacology (5th ed.). Philadelphia, Pa.: Lippincott Williams & Wilkins. ISBN 978-0781728379.
  11. ^ Seim I, Amorim L, Walpole C, Carter S, Chopin LK, Herington AC (January 2010). "Ghrelin gene-related peptides: multifunctional endocrine / autocrine modulators in health and disease". Clinical and Experimental Pharmacology & Physiology. 37 (1): 125–31. doi:10.1111/j.1440-1681.2009.05241.x. PMID 19566830.
  12. ^ a b Castañeda TR, Tong J, Datta R, Culler M, Tschöp MH (January 2010). "Ghrelin in the regulation of body weight and metabolism". Frontiers in Neuroendocrinology. 31 (1): 44–60. doi:10.1016/j.yfrne.2009.10.008. PMID 19896496.
  13. ^ Bedendi I, Alloatti G, Marcantoni A, Malan D, Catapano F, Ghé C, et al. (August 2003). "Cardiac effects of ghrelin and its endogenous derivatives des-octanoyl ghrelin and des-Gln14-ghrelin" (PDF). European Journal of Pharmacology. 476 (1–2): 87–95. doi:10.1016/S0014-2999(03)02083-1. hdl:2318/125949. PMID 12969753.
  14. ^ Toshinai K, Yamaguchi H, Sun Y, Smith RG, Yamanaka A, Sakurai T, et al. (May 2006). "Des-acyl ghrelin induces food intake by a mechanism independent of the growth hormone secretagogue receptor". Endocrinology. 147 (5): 2306–14. doi:10.1210/en.2005-1357. PMID 16484324.
  15. ^ Gauna C, Delhanty PJ, Hofland LJ, Janssen JA, Broglio F, Ross RJ, et al. (February 2005). "Ghrelin stimulates, whereas des-octanoyl ghrelin inhibits, glucose output by primary hepatocytes". The Journal of Clinical Endocrinology and Metabolism. 90 (2): 1055–60. doi:10.1210/jc.2004-1069. PMID 15536157.
  16. ^ Korbonits M, Goldstone AP, Gueorguiev M, Grossman AB (April 2004). "Ghrelin--a hormone with multiple functions". Frontiers in Neuroendocrinology. 25 (1): 27–68. doi:10.1016/j.yfrne.2004.03.002. PMID 15183037.
  17. ^ a b Stengel A, Taché Y (June 2011). "Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage". Current Protein & Peptide Science. 12 (4): 293–304. doi:10.2174/138920311795906673. PMC 3670092. PMID 21428875.
  18. ^ Zigman JM, Nakano Y, Coppari R, Balthasar N, Marcus JN, Lee CE, et al. (December 2005). "Mice lacking ghrelin receptors resist the development of diet-induced obesity". The Journal of Clinical Investigation. 115 (12): 3564–72. doi:10.1172/JCI26002. PMC 1297251. PMID 16322794.
  19. ^ Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, et al. (October 2001). "Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans". The Journal of Clinical Endocrinology and Metabolism. 86 (10): 4753–8. doi:10.1210/jcem.86.10.7885. PMID 11600536.
  20. ^ Suckale J, Solimena M (May 2008). "Pancreas islets in metabolic signaling--focus on the beta-cell". Frontiers in Bioscience. 13 (13): 7156–71. doi:10.2741/3218. PMID 18508724.
  21. ^ Ferrini F, Salio C, Lossi L, Merighi A (March 2009). "Ghrelin in central neurons". Current Neuropharmacology. 7 (1): 37–49. doi:10.2174/157015909787602779. PMC 2724662. PMID 19721816.
  22. ^ Simonsson M, Eriksson S, Håkanson R, Lind T, Lönroth H, Lundell L, et al. (November 1988). "Endocrine cells in the human oxyntic mucosa. A histochemical study". Scandinavian Journal of Gastroenterology. 23 (9): 1089–99. doi:10.3109/00365528809090174. PMID 2470131.
  23. ^ Grube D, Forssmann WG (November 1979). "Morphology and function of the entero-endocrine cells". Hormone and Metabolic Research = Hormon- und Stoffwechselforschung = Hormones et Metabolisme. 11 (11): 589–606. doi:10.1055/s-0028-1092785. PMID 94030.
  24. ^ Fukumoto K, Nakahara K, Katayama T, Miyazatao M, Kangawa K, Murakami N (September 2008). "Synergistic action of gastrin and ghrelin on gastric acid secretion in rats". Biochemical and Biophysical Research Communications. 374 (1): 60–3. doi:10.1016/j.bbrc.2008.06.114. PMID 18611393.
  25. ^ Inhoff T, Stengel A, Peter L, Goebel M, Taché Y, Bannert N, et al. (February 2010). "Novel insight in distribution of nesfatin-1 and phospho-mTOR in the arcuate nucleus of the hypothalamus of rats". Peptides. 31 (2): 257–62. doi:10.1016/j.peptides.2009.11.024. PMC 4043136. PMID 19961888.
  26. ^ Arnes L, Hill JT, Gross S, Magnuson MA, Sussel L (2012). "Ghrelin expression in the mouse pancreas defines a unique multipotent progenitor population". PLOS ONE. 7 (12): e52026. Bibcode:2012PLoSO...752026A. doi:10.1371/journal.pone.0052026. PMC 3520898. PMID 23251675.
  27. ^ a b Yokota I, Kitamura S, Hosoda H, Kotani Y, Kangawa K (April 2005). "Concentration of the n-octanoylated active form of ghrelin in fetal and neonatal circulation". Endocrine Journal. 52 (2): 271–6. doi:10.1507/endocrj.52.271. PMID 15863960.
  28. ^ Tolle V, Bassant MH, Zizzari P, Poindessous-Jazat F, Tomasetto C, Epelbaum J, Bluet-Pajot MT (April 2002). "Ultradian rhythmicity of ghrelin secretion in relation with GH, feeding behavior, and sleep-wake patterns in rats". Endocrinology. 143 (4): 1353–61. doi:10.1210/endo.143.4.8712. PMID 11897692.
  29. ^ Yin Y, Li Y, Zhang W (March 2014). "The growth hormone secretagogue receptor: its intracellular signaling and regulation". International Journal of Molecular Sciences. 15 (3): 4837–55. doi:10.3390/ijms15034837. PMC 3975427. PMID 24651458.
  30. ^ Heppner KM, Tong J (July 2014). "Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions". European Journal of Endocrinology. 171 (1): R21-32. doi:10.1530/EJE-14-0183. PMID 24714083.
  31. ^ Zhu B, Shi C, Park CG, Zhao X, Reutrakul S (June 2019). "Effects of sleep restriction on metabolism-related parameters in healthy adults: A comprehensive review and meta-analysis of randomized controlled trials". Sleep Medicine Reviews. 45: 18–30. doi:10.1016/j.smrv.2019.02.002. PMID 30870662.
  32. ^ Comninos AN, Jayasena CN, Dhillo WS (2014). "The relationship between gut and adipose hormones, and reproduction". Human Reproduction Update. 20 (2): 153–74. doi:10.1093/humupd/dmt033. PMID 24173881.
  33. ^ Santos M, Bastos P, Gonzaga S, Roriz JM, Baptista MJ, Nogueira-Silva C, et al. (April 2006). "Ghrelin expression in human and rat fetal lungs and the effect of ghrelin administration in nitrofen-induced congenital diaphragmatic hernia". Pediatric Research. 59 (4 Pt 1): 531–7. doi:10.1203/01.pdr.0000202748.66359.a9. PMID 16549524.
  34. ^ Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, et al. (January 2002). "Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion". The Journal of Clinical Endocrinology and Metabolism. 87 (1): 240–4. doi:10.1210/jcem.87.1.8129. PMID 11788653.
  35. ^ Goldstone AP, Thomas EL, Brynes AE, Castroman G, Edwards R, Ghatei MA, et al. (April 2004). "Elevated fasting plasma ghrelin in prader-wili syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance". The Journal of Clinical Endocrinology and Metabolism. 89 (4): 1718–26. doi:10.1210/jc.2003-031118. PMID 15070936.
  36. ^ Goldstone AP, Thomas EL, Brynes AE, Castroman G, Edwards R, Ghatei MA, et al. (April 2004). "Elevated fasting plasma ghrelin in prader-wili syndrome adults is not solely explained by their reduced visceral adiposity and insulin resistance". The Journal of Clinical Endocrinology and Metabolism. 89 (4): 1718–26. doi:10.1210/jc.2003-031118. PMID 15070936.
  37. ^ Misra M, Klibanski A (July 2014). "Endocrine consequences of anorexia nervosa". The Lancet. Diabetes & Endocrinology. 2 (7): 581–92. doi:10.1016/S2213-8587(13)70180-3. PMC 4133106. PMID 24731664.
  38. ^ Tolle V, Kadem M, Bluet-Pajot MT, Frere D, Foulon C, Bossu C, et al. (January 2003). "Balance in ghrelin and leptin plasma levels in anorexia nervosa patients and constitutionally thin women". The Journal of Clinical Endocrinology and Metabolism. 88 (1): 109–16. doi:10.1210/jc.2002-020645. PMID 12519838.
  39. ^ Germain N, Galusca B, Le Roux CW, Bossu C, Ghatei MA, Lang F, et al. (April 2007). "Constitutional thinness and lean anorexia nervosa display opposite concentrations of peptide YY, glucagon-like peptide 1, ghrelin, and leptin". The American Journal of Clinical Nutrition. 85 (4): 967–71. doi:10.1093/ajcn/85.4.967. PMID 17413094.
  40. ^ Yildiz BO, Suchard MA, Wong ML, McCann SM, Licinio J (July 2004). "Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity". Proceedings of the National Academy of Sciences of the United States of America. 101 (28): 10434–9. Bibcode:2004PNAS..10110434Y. doi:10.1073/pnas.0403465101. PMC 478601. PMID 15231997.
  41. ^ Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D, et al. (May 2005). "Active ghrelin levels and active to total ghrelin ratio in cancer-induced cachexia". The Journal of Clinical Endocrinology and Metabolism. 90 (5): 2920–6. doi:10.1210/jc.2004-1788. PMID 15713718.
  42. ^ Khatib MN, Shankar AH, Kirubakaran R, Gaidhane A, Gaidhane S, Simkhada P, Quazi Syed Z (February 2018). "Ghrelin for the management of cachexia associated with cancer". The Cochrane Database of Systematic Reviews. 2: CD012229. doi:10.1002/14651858.cd012229.pub2. PMC 6491219. PMID 29489032.
  43. ^ Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ (May 2002). "Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery". The New England Journal of Medicine. 346 (21): 1623–30. doi:10.1056/NEJMoa012908. PMID 12023994.
  44. ^ Cummings DE, Shannon MH (July 2003). "Ghrelin and gastric bypass: is there a hormonal contribution to surgical weight loss?". The Journal of Clinical Endocrinology and Metabolism. 88 (7): 2999–3002. doi:10.1210/jc.2003-030705. PMID 12843132.
  45. ^ Bohdjalian A, Langer FB, Shakeri-Leidenmühler S, Gfrerer L, Ludvik B, Zacherl J, Prager G (May 2010). "Sleeve gastrectomy as sole and definitive bariatric procedure: 5-year results for weight loss and ghrelin". Obesity Surgery. 20 (5): 535–40. doi:10.1007/s11695-009-0066-6. PMID 20094819.
Retrieved from "https://en.wikipedia.org/w/index.php?title=User:Amymy0731/sandbox&oldid=952202075"