Ghreline - het honger hormoon
Heb je vaak een hongergevoel ?
Grote kans dat je maag veel van het
hormoon Ghreline aanmaakt dat een signaal naar je hersenen stuurt. Zodra de maag gevuld is
neemt de aanmaak van dit hormoon af en stopt het hongergevoel. Daarnaast reageren je
darmen op calorierijk voedsel, zodra de darm zich vult worden er bepaalde eiwitten
aangemaakt zoals de stof PYY die juist de trek vermindert. Het is dus een samenspel van
hormonen en eiwitten die je hongergevoel aansturen. Gaat daar wat mis dan is het ook
logisch dat de ene persoon een sterker hongergevoel heeft dan de andere. Misschien speelt
de Hoodia cactus ook wel een rol bij dit proces. Want deze zorgt ook voor een verminderd
hongergevoel. Waarschijnlijk saboteert deze het proces van hormonen en eiwitten. Unilever
kreeg dollars in de ogen en betaalde zonder een kik 50 miljoen euros voor de rechten van
de synthetische stof P57 in deze cactus. Je begrijpt dat een honger blocker goud geld
waard is maar ook riskant voor mensen is die dit te fanatiek zouden gaan gebruiken en
drastisch willen lijnen. Het verdere research naar deze stof zal nog wel enige jaren duren
maar ik denk dat er een hele lijn van nieuwe dieet produkten zal volgen.
Ron
Oplossing voor diabetes en
overgewicht
Het is een complexe balans van signalen
die lopen van maagdarmkanaal naar hypothalamus, naar hypofyse en hersenstam. Uiteindelijk
wordt in de hersenen via een ingewikkelde beslissingsprocedure de maaltijdgrootte
vastgesteld. Interessant is onze bevinding dat PYY de insulinegevoeligheid van
diabetesmuizen lijkt te verbeteren. We hopen dat dit de weg wijst naar een nieuw
diabetesmedicijn.
http://www.lumc.nl/1080/uitgaven/pdf/2004nr14.pdf
Artsen geven ghrelineblokkers
weinig kans
De farmaceutische industrie zoekt koortsachtig naar een medicijn tegen vetzucht. Eén van
de mogelijke nieuwe middelen grijpen aan op het hormoon ghreline, dat eetlust veroorzaakt.
Toch denken artsen niet dat ghrelineblokkers veel effect zullen hebben.
http://www.ergogenics.org/ghreline.html
Proefschrift Wendy Blom
Wendy Blom deed onderzoek naar de werking
van dit hormoon voor haar proefschrift. Er wordt oa een relatie gevonden tussen de
concentraties Ghreline en de eetlust. Het eerste stuk is Engelstalig maar op het eind vind
je een Nederlandse samenvatting.
In haar proefschrift 'Regulation of food
intake: A focus on ghrelin geeft Wendy aan dat er aanwijzingen zijn dat het hormoon
ghreline een belangrijk hongersignaal is. Uit haar onderzoek blijkt dat de veranderingen
in ghreline concentraties in het bloed positief gerelateerd zijn aan veranderingen in
eetlust. Ghreline is een korte termijn honger signaal, het bepaalt niet wanneer je stopt
met eten (en hoeveel je eet), maar lijkt te bepalen wanneer je begint te eten. Het is
noodzakelijk om meer inzicht te krijgen in de processen die ervoor zorgen dat mensen gaan
eten of stoppen met eten. Dit stelt ons in staat om bij de ontwikkeling van nieuwe
voedingsmiddelen een nutriënt mee te nemen (bijvoorbeeld melkeiwit) dat ghreline
concentraties kan onderdrukken. Deze nutriënten zouden kunnen helpen bij de preventie van
overgewicht en obesitas.
http://www.tno.nl/kwaliteit_van_leven/actueel/2005/hormoon_ghreline
Leer met lege maag
'Hongerhormoon' stimuleert geheugen en
leervermogen
Een hormoon dat eerst alleen in verband werd gebracht met honger, blijkt ook invloed uit
te oefenen op het geheugen en het vermogen om te leren.
Een tip voor scholieren, studenten en
anderen die aan de vooravond staan van een belangrijke toets of examen: eet niet. Het
geheugen werkt beter op een lege maag, zo schrijven onderzoekers in Nature Neuroscience.
Natuurlijk is het niet de bedoeling zo
weinig te eten, dat je tijdens het examen voor pampus ligt. Het is een kwestie van de
balans vinden tussen net genoeg eten om bij te blijven en net te weinig om de maag te
vullen. Amerikaanse wetenschappers ontdekten dat een hormoon dat wordt geassocieerd met
hongergevoelens ook invloed heeft op leergedrag en het geheugen.
Dit 'hongerhormoon' heet ghreline. Het
wordt uitgescheiden door de maag als daar te weinig voedsel in zit. Via het bloed komt het
ghreline in de hypothalamus terecht en dat stimuleert vervolgens de eetlust. Het leek er
echter op dat de hypothalamus niet het enige hersengebied is waar ghreline terecht komt.
Wetenschappers zagen eerder dat ook de zenuwcellen van de hippocampus, waar zich het
geheugen en het vermogen te leren bevinden, ghreline konden binden. Een reden voor Sabrina
Diano van de Amerikaanse Yale-Universeit en haar collega's om uit te zoeken wat het
hongerhormoon daar dan precies te zoeken heeft.
http://noorderlicht.vpro.nl/artikelen/27300074/
Eiwitten remmen hongerhormoon
Na een maaltijd met veel zuiveleiwitten
duurt het langer voordat je weer honger krijgt, ontdekte een Wageningse promovenda. Als je
er tenminste genoeg van binnenkrijgt remmen de eiwitten de aanmaak van een hormoon dat
hongergevoel veroorzaakt.
http://www.wb-online.nl/index.php?/krant/artikel.php?id=2338
Te weinig slaap maakt dik,
steiging Ghreline niveau
Deze studie
suggereert dus dat slaaptekort, een verschijnsel dat in onze moderne maatschappij alsmaar
meer voorkomt, een rol zou kunnen spelen bij de overconsumptie van energie en bij
obesitas. Alhoewel bijkomend onderzoek nodig is, wijzen we nog op een andere studie op
grotere schaal (1024 deelnemers), op dezelfde dag gepubliceerd, waarvan de resultaten in
dezelfde zin gaan: bij mensen die minder dan 8 uur per 24 uur slapen, is er een stijging
van de BMI in verhouding tot de vermindering van de slaaptijd (2). De auteurs vermelden
dat het verminderen van de slaap van 8 uur naar 5 uur gepaard gaat met een daling van de
leptineconcentratie met 15,5 % en een stijging van de ghrelineconcentratie met 14,9 %.
http://www.healthandfood.be/html/nl/news/2004/2004-12-08.htm
Amerikaans bedrijf krijgt
versnelde FDA procedure voor medicijn op basis van het hormoon Ghreline. Dit is bestemd
voor mensen die leiden aan kanker en daarbij gewichtsverlies/anorexia hebben wat voor
levensbedreigende situaties kan zorgen.
Rejuvenon's RC-1291 Ghrelin Mimetic
Receives Fast Track Designation from FDA for Cancer Anorexia/Cachexia
Rejuvenon Corporation, a privately held
pharmaceutical company developing therapeutics for cancer and metabolic disorders, has
received US Food and Drug Administration (FDA) "fast track" designation for its
investigational compound, RC-1291, a small-molecule ghrelin mimetic, for the treatment of
cachexia (loss of body weight) and anorexia (loss of appetite) in cancer patients. The
anorexia/cachexia syndrome is a common, life-threatening complication of underlying
malignancies.
"There is a significant unmet need
for a pharmaceutical treatment in cancer cachexia," said Gary C. Cupit, PharmD,
president and chief executive officer of Rejuvenon. "Unexpected weight loss is an
all-too-common and devastating consequence of cancer. Currently, effective treatments are
lacking and the patient population in need of an effective treatment is substantial.
Clinicians and patients are seeking a product that offers the potential we see in
Rejuvenon's lead candidate, RC-1291."
The fast-track programs of the FDA are
designed to facilitate the development and expedite the review of new drugs intended to
treat serious or life-threatening conditions and that demonstrate the potential to address
unmet medical needs. In its letter to Rejuvenon, the FDA stated that based on preclinical
and early clinical data, RC-1291 shows potential as a treatment for cancer
anorexia/cachexia. This syndrome frequently accompanies malignant disease states and often
results in the death of the patient. In these patients, weight loss is an independent risk
factor for poor survival, and cachectic patients also suffer increased complications from
surgery, radiotherapy, and chemotherapy. To date, there are no effective treatments
approved for this indication.
"Preclinical and clinical data have
demonstrated the potent appetite-stimulating effects of RC-1291," said William J.
Polvino, MD, Rejuvenon's senior vice president of development. "In addition, RC-1291
has potential anabolic attributes that we expect to reduce or eliminate the ongoing loss
of body weight and/or muscle mass. No other agent provides the dual actions of potent
appetite stimulation and anabolic activity. Consequently RC-1291 represents an important
therapeutic prospect in the treatment of cancer anorexia/cachexia. We expect intervention
with RC-1291 to improve appetite and food intake and attenuate or reverse ongoing weight
loss. Additional benefits may include improvements in quality of life and functional
performance."
About Ghrelin and RC-1291
The recent discovery of ghrelin-mediated
effects on appetite opens a new avenue for pharmaceutical treatment. Ghrelin is a small
endogenous protein that acts on the Growth Hormone Secretagogue Receptor (GHSR), a
G-Protein Coupled Receptor recognized as a key control point in the growth hormone
signaling pathway. The GHSR is a target for treatment of several metabolic disorders
including those related to maintenance of ideal body weight and composition. Agonists for
this receptor have been identified as drug candidates for treatment of wasting and body
fat redistribution syndromes associated with a range of diseases, such as cancer and AIDS.
However, potential clinical use of ghrelin itself for wasting disorders is limited,
because it must be administered by injection.
RC-1291 is a synthetic, small-molecule
ghrelin mimetic that binds to, and stimulates, the GHSR. Unlike ghrelin, RC-1291 can be
delivered by mouth. This highly potent, orally available compound is intended to be
administered as a convenient once-daily treatment for patients with cancer
anorexia/cachexia. The compound has been studied in a series of seven completed or ongoing
clinical studies in human volunteers, including a double-blind placebo-controlled study in
which, compared to placebo, RC-1291 significantly increased appetite and spontaneous food
intake. Under the FDA fast-track designation, Rejuvenon plans to conduct Phase II trials
later this year.
In addition to the known stimulation of
appetite and food intake via central orexigenic pathways, additional mechanisms of action
of RC-1291 may be relevant in treating cancer anorexia/cachexia. Loss of appetite and body
weight associated with cancer is somewhat driven by circulating inflammatory cytokines
such as TNF-alpha (originally named "cachectin") and IL-6. Recent studies have
shown that activation of the ghrelin receptor may play a direct role in reducing the
production and circulating levels of inflammatory cytokines such as TNF-alpha. Ghrelin and
RC-1291 are both highly potent agonists at the same receptor, thus experimental data
generated with ghrelin help to validate use of RC-1291 in cancer anorexia/cachexia.
Dr. Cupit added, "Our lead program
is a superb example of the dynamic synergy of Rejuvenon's big pharma/biotech partnering
strategy. We are delighted that the development team has reached this milestone so rapidly
from a preclinical candidate into Phase II. We are equally pleased with the consensus
between Rejuvenon and the FDA in recognizing cancer anorexia/cachexia as an important
unmet medical need. Our efforts are now focused on speeding the development of RC-1291 by
generating the data needed to bring the product to market. Believing that this represents
the first of many potential opportunities, we will continue to leverage the skills of our
expanding development team through additional product acquisitions."
About Rejuvenon
Rejuvenon, founded in 2000 by Dr. Roy G.
Smith of the Baylor College of Medicine, is a private pharmaceutical development company
whose strategy is to in-license and develop promising drug candidates that are ready for
preclinical or clinical testing. The company is developing small molecule drugs to treat
metabolic and oncologic diseases for which existing therapies are limited or marginally
effective. Rejuvenon's first portfolio of drug candidates were in-licensed as preclinical
compounds from Novo Nordisk in May 2001. RC-1291 is the furthest advanced of this series
of orally-deliverable compounds for treatment of cancer-related weight loss. The company
is moving several additional molecules through preclinical development. As development
proceeds on these compounds, Rejuvenon is actively seeking other preclinical in-licensing
candidates to fill the development pipeline.
Studies
1. Corbetta, S.; Peracchi, M.; Cappiello,
V.; Lania, A.; Lauri, E.; Vago, L.; Beck-Peccoz, P.; Spada, A. :
Circulating ghrelin levels in patients with pancreatic and gastrointestinal neuroendocrine
tumors: identification of one pancreatic ghrelinoma. J. Clin. Endocr. Metab. 88:
3117-3120, 2003. PubMed ID : 12843152
2. Cowley, M. A.; Smith, R. G.; Diano,
S.; Tschop, M.; Pronchuk, N.; Grove, K. L.; Strasburger, C. J.; Bidlingmaier, M.;
Esterman, M.; Heiman, M. L.; Garcia-Segura, L. M.; Nillni, E. A.; and 9 others :
The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel
hypothalamic circuit regulating energy homeostasis. Neuron 37: 649-661, 2003. PubMed
ID : 12597862
3. Cummings, D. E.; Weigle, D. S.; Frayo,
R. S.; Breen, P. A.; Ma, M. K.; Dellinger, E. P.; Purnell, J. Q. :
Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. New Eng.
J. Med. 346: 1623-1630, 2002. PubMed ID : 12023994
4. Date, Y.; Kojima, M.; Hosoda, H.;
Sawaguchi, A.; Mondal, M. S.; Suganuma, T.; Matsukura, S.; Kangawa, K.; Nakazato, M. :
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, 2000. PubMed ID : 11089560
5. Date, Y.; Nakazato, M.; Murakami, N.;
Kojima, M.; Kangawa, K.; Matsukura, S. :
Ghrelin acts in the central nervous system to stimulate gastric acid secretion. Biochem.
Biophys. Res. Commun. 280: 904-907, 2001.
PubMed ID : 11162609
6. Delparigi, A.; Tschop, M.; Heiman, M.
L.; Salbe, A. D.; Vozarova, B.; Sell, S. M.; Bunt, J. C.; Tataranni, P. A. :
High circulating ghrelin: a potential cause for hyperphagia and obesity in Prader-Willi
syndrome. J. Clin. Endocr. Metab. 87: 5461-5464, 2002.
PubMed ID : 12466337
7. Dixit, V. D.; Schaffer, E. M.; Pyle,
R. S.; Collins, G. D.; Sakthivel, S. K.; Palaniappan, R.; Lillard, J. W., Jr.; Taub, D. D.
:
Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by
human monocytes and T cells. J. Clin. Invest. 114: 57-66, 2004. PubMed ID : 15232612
8. Farquhar, J.; Heiman, M.; Wong, A. C.
K.; Wach, R.; Chessex, P.; Chanoine, J.-P. :
Elevated umbilical cord ghrelin concentrations in small for gestational age neonates. J.
Clin. Endocr. Metab. 88: 4324-4327, 2003.
PubMed ID : 12970305
9. Haqq, A. M.; Farooqi, I. S.;
O'Rahilly, S.; Stadler, D. D.; Rosenfeld, R. G.; Pratt, K. L.; LaFranchi, S. H.; Purnell,
J. Q. :
Serum ghrelin levels are inversely correlated with body mass index, age, and insulin
concentrations in normal children and are markedly increased in Prader-Willi syndrome. J.
Clin. Endocr. Metab. 88: 174-178, 2003.
PubMed ID : 12519848
10. Hinney, A.; Hoch, A.; Geller, F.;
Schafer, H.; Siegfried, W.; Goldschmidt, H.; Remschmidt, H.; Hebebrand, J. :
Ghrelin gene: identification of missense variants and a frameshift mutation in extremely
obese children and adolescents and healthy normal weight students. J. Clin. Endocr. Metab.
87: 2716-2719, 2002. PubMed ID : 12050239
11. Kojima, M.; Hosoda, H.; Date, Y.;
Nakazato, M.; Matsuo, H.; Kangawa, K. :
Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402: 656-660,
1999. PubMed ID : 10604470
12. Kojima, M.; Hosoda, H.; Matsuo, H.;
Kangawa, K. :
Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue
receptor. Trends Endocr. Metab. 12: 118-126, 2001.
13. Korbonits, M.; Gueorguiev, M.;
O'Grady, E.; Lecoeur, C.; Swan, D. C.; Mein, C. A.; Weill, J.; Grossman, A. B.; Froguel,
P. :
A variation in the ghrelin gene increases weight and decreases insulin secretion in tall,
obese children. J. Clin. Endocr. Metab. 87: 4005-4008, 2002. PubMed ID : 12161552
14. Leonetti, F.; Silecchia, G.;
Iacobellis, G.; Ribaudo, M. C.; Zappaterreno, A.; Tiberti, C.; Iannucci, C. V.; Perrotta,
N.; Bacci, V.; Basso, M. S.; Basso, N.; Di Mario, U. :
Different plasma ghrelin levels after laparoscopic gastric bypass and adjustable gastric
banding in morbid obese subjects. J. Clin. Endocr. Metab. 88: 4227-4231, 2003. PubMed ID :
12970291
15. Nakazato, M.; Murakami, N.; Date, Y.;
Kojima, M.; Matsuo, H.; Kangawa, K.; Matsukura, S. :
A role for ghrelin in the central regulation of feeding. Nature 409: 194-198, 2001. PubMed
ID : 11196643
16. Pagotto, U.; Gambineri, A.; Pelusi,
C.; Genghini, S.; Cacciari, M.; Otto, B.; Castaneda, T.; Tschop, M.; Pasquali, R. :
Testosterone replacement therapy restores normal ghrelin in hypogonadal men. J. Clin.
Endocr. Metab. 88: 4139-4143, 2003.
PubMed ID : 12970277
17. Popovic, V.; Miljic, D.; Micic, D.;
Damjanovic, S.; Arvat, E.; Ghigo, E.; Dieguez, C.; Casanueva, F. F. :
Ghrelin main action on the regulation of growth hormone release is exerted at hypothalamic
level. J. Clin. Endocr. Metab. 88: 3450-3453, 2003.
PubMed ID : 12843202
18. Scott, A. F. :
Personal Communication. Baltimore, Md., 10/24/2000.
19. Takaya, K.; Ariyasu, H.; Kanamoto,
N.; Iwakura, H.; Yoshimoto, A.; Harada, M.; Mori, K.; Komatsu, Y.; Usui, T.; Shimatsu, A.;
Ogawa, Y.; Hosoda, K.; Akamizu, T.; Kojima, M.; Kangawa, K.; Nakao, K. :
Ghrelin strongly stimulates growth hormone (GH) release in humans. J. Clin. Endocr. Metab.
85: 4908-4911, 2000.
PubMed ID : 11134161
20. Tanaka, M.; Hayashida, Y.; Nakao, N.;
Nakai, N.; Nakashima, K. :
Testis-specific and developmentally induced expression of a ghrelin gene-derived
transcript that encodes a novel polypeptide in the mouse. Biochim. Biophys. Acta 1522:
62-65, 2001.
PubMed ID : 11718902
21. Tschop, M.; Smiley, D. L.; Heiman, M.
L. :
Ghrelin induces adiposity in rodents. Nature 407: 908-913, 2000.
PubMed ID : 11057670
22. Ukkola, O.; Ravussin, E.; Jacobson,
P.; Snyder, E. E.; Chagnon, M.; Sjostrom, L.; Bouchard, C. :
Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J. Clin.
Endocr. Metab. 86: 3996-3999, 2001.
PubMed ID : 11502844
23. Wortley, K. E.; Anderson, K. D.;
Garcia, K.; Murray, J. D.; Malinova, L.; Liu, R.; Moncrieffe, M.; Thabet, K.; Cox, H. J.;
Yancopoulos, G. D.; Wiegand, S. J.; Sleeman, M. W. : Genetic deletion of ghrelin does not
decrease food intake but influences metabolic fuel preference. Proc. Nat. Acad. Sci. 101:
8227-8232, 2004. PubMed ID : 15148384
24. Wortley, K. E.; del Rincon, J.-P.;
Murray, J. D.; Garcia, K.; Iida, K.; Thorner, M. O.; Sleeman, M. W. : Absence of ghrelin
protects against early-onset obesity. J. Clin. Invest. 115: 3573-3578, 2005.
PubMed ID : 16322795
25. Zhang, J. V.; Ren, P.-G.;
Avsian-Kretchmer, O.; Luo, C.-W.; Rauch, R.; Klein, C.; Hsueh, A. J. W. :
Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food
intake. Science 310: 996-999, 2005.
PubMed ID : 16284174
26. Zigman, J. M.; Nakano, Y.; Coppari,
R.; Balthasar, N.; Marcus, J. N.; Lee, C. E.; Jones, J. E.; Deysher, A. E.; Waxman, A. R.;
White, R. D.; Williams, T. D.; Lachey, J. L.; Seeley, R. J.; Lowell, B. B.; Elmquist, J.
K. :
Mice lacking ghrelin receptors resist the development of diet-induced obesity. J. Clin.
Invest. 115: 3564-3572, 2005.
PubMed ID : 16322794
Studies in Japan
Kojima M, Hosoda H, Date Y, Nakazato M,
Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach.
Nature 402: 656-660, 1999.
Hosoda H, Kojima M, Matsuo H, Kangawa K:
Ghrelin and des-acyl ghrelin: two major forms of rat ghrelin peptide in gastrointestinal
tissue. Biochem Biophys Res Commun 279: 909-913, 2000.
Date Y, Kojima M, Hosoda H, Sawaguchi A,
Mondal M S, Suganuma T, Matsukura S, Kangawa K, Nakazato M: 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, 2000.
Hosoda H, Kojima M, Matsuo H, Kangawa K:
Purification and characterization of rat des-Gln14-Ghrelin, a second endogenous ligand for
the growth hormone secretagogue receptor. J Biol Chem 275: 21995-22000, 2000.
Matsuo H, Kojima M, Hayashi Y, Kangawa K:
Structure-activity relationship of ghrelin: pharmacological study of ghrelin peptides.
Biochem Biophys Res Commun. 287: 142-146, 2001.
Matsumoto M, Kitajima Y, Iwanami T,
Hayashi Y, Tanaka S, Minamitake Y, Hosoda H, Kojima M, Matsuo H, Kangawa K: Structural
similarity of ghrelin derivatives to peptidyl growth hormone secretagogues. Biochem
Biophys Res Commun. 284: 655-659, 2001.
Kaiya H, Kojima M, Hosoda H, Koda A,
Yamamoto K, Kitajima Y, Matsumoto M, Minamitake Y, Kikuyama S, Kangawa K: Bullfrog ghrelin
is modified by n-octanoic acid at its third threonine residue. J Biol Chem 276:
40441-40448, 2001.
Ariyasu H, Takaya K, Tagami T, Ogawa Y,
Hosoda K, Akamizu T, Suda M, Koh T, Natsui K, Toyooka S, Shirakami G, Usui T, Shimatsu A,
Doi K, Hosoda H, Kojima M, Kangawa K, Nakao K: Stomach is a major source of circulating
ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in
humans. J Clin Endocrinol Metab 86: 4753-4758, 2001.
Kaiya H, Van Der Geyten S, Kojima M,
Hosoda H, Kitajima Y, Matsumoto M, Geelissen S, Darras VM, Kangawa K: Chicken ghrelin:
purification, cDNA cloning, and biological activity. Endocrinology. 143: 3454-3463, 2002.
Shiiya T, Nakazato M, Mizuta M, Date Y,
Mondal MS, Tanaka M, Nozoe S, Hosoda H, Kangawa K, Matsukura S. Plasma ghrelin levels in
lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol
Metab 87: 240-244, 2002.
Lu S, Guan JL, Wang QP, Uehara K, Yamada
S, Goto N, Date Y, Nakazato M, Kojima M, Kangawa K, Shioda S: Immunocytochemical
observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci Lett. 321:
157-160, 2002.
Date Y, Nakazato M, Hashiguchi S, Dezaki
K, Mondal M S, Hosoda H, Kojima M, Kangawa K, Arima T, Matsuo H, Yada T, Matsukura S:
Ghrelin is present in pancreatic alpha-cells of humans and rats and stimulates insulin
secretion. Diabetes 51: 124-129, 2002.
Kaiya H, Kojima M, Hosoda H, Riley LG,
Hirano T, Grau EG, Kangawa K: Amidated fish ghrelin: purification, cDNA cloning in the
Japanese eel and its biological activity. J Endocrinol. 176: 415-423, 2003.
Kaiya H, Kojima M, Hosoda H, Riley LG,
Hirano T, Grau EG, Kangawa K: Identification of tilapia ghrelin and its effects on growth
hormone and prolactin release in the tilapia, Oreochromis mossambicus. Comp Biochem
Physiol B Biochem Mol Biol 135: 421-429, 2003.
Kaiya H, Kojima M, Hosoda H, Moriyama S,
Takahashi A, Kawauchi H, Kangawa K: Peptide purification, complementary deoxyribonucleic
acid (DNA) and genomic DNA cloning, and functional characterization of ghrelin in rainbow
trout. Endocrinology 144: 5215-5226, 2003.
Shimada M, Date Y, Mondal MS, Toshinai K,
Shimbara T, Fukunaga K, Murakami N, Miyazato M, Kangawa K, Yoshimatsu H, Matsuo H,
Nakazato M: Somatostatin suppresses ghrelin secretion from the rat stomach. Biochem
Biophys Res Commun 302: 520-525, 2003.
Hosoda H, Kojima M, Mizushima T, Shimizu
S, Kangawa K: Structural divergence of human ghrelin. Identification of multiple
ghrelin-derived molecules produced by post-translational processing. J Biol Chem 278:
64-70, 2003.
Kaiya H, Sakata I, Kojima M, Hosoda H,
Sakai T, Kangawa K: Structural determination and histochemical localization of ghrelin in
the red-eared slider turtle, Trachemys scripta elegans. Gen Comp Endocrinol 138: 50-57,
2004.
Meer informatie over deze studies en
onderzoekers die met name onderzoek doen naar Ghreline
http://www.ncvc.go.jp/english/res/Bio.html
Ghrelin and the Future of Weight
Loss
Many researchers believe that ghrelin
plays a significant role in the long-term regulation of body weight. They suggest that
excessive production of ghrelin may be a factor in many cases of morbid obesity. But what
accounts for increasing rate of obesity in recent years? Are people simply producing more
ghrelin?
Most nutrition and obesity experts
attribute the increasing rate of obesity to modern lifestyle factors such as increased
consumption of high-calorie foods and lack of regular exercise. Many people try to diet to
lose weight but do not make permanent and sustainable changes in their eating and exercise
habits. Since most dieting involves food and calorie-restriction, it is often unsuccessful
simply because it is monotonous, restrictive, and causes hunger. But, according to the
experts, most people can achieve a healthful weight and body fat level by making permanent
and palatable changes in their eating habits and getting regular exercise.
Its possible that in the near
future, drug companies will develop a drug that blocks ghrelin. This would help reduce
excess hunger and weight gain. In the meantime, additional studies are being conducted in
this exciting new branch of obesity research.
http://www.swedish.org/17365.cfm
Biggest moneymaker that any drug
company's ever seen
Ghrelin, discovered about two years ago,
has a role in promoting growth, from making children taller to building bone density.
Injecting the hormone in rodents makes them eat right away, but ghrelin has not been
proven to stimulate appetite in people. Still, several major pharmaceutical companies are
trying to develop drugs to block the hormone, Cummings said. "A true cure for obesity
would be the biggest moneymaker that any drug company's ever seen,'' he said.
http://www.phoenixpeptide.com/Catalog%20Files/Ghrelin%20Section/ghrelin.htm
More References of
Ghrelin
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