Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice

Thulesen, Jesper; Hartmann, Bolette; Hare, Kristine Juul; Kissow, Hannelouise; Ørskov, Cathrine; Holst, Jens J.; Poulsen, Steen Seier

doi:10.1136/gut.2003.035212

Cited by 101 publications

(73 citation statements)

References 28 publications

(13 reference statements)

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“…For example, FGF also induces stricture formation in Crohn's disease [57] and GLP-2 might have undesired effects in tumorogenesis [58] , which might limit their therapeutic use. In addition, it has to be considered that these factors and also various non-peptide factors may act in an additive or even synergistic fashion which may potentiate their single effects.…”

Section: The Role Of Regulatory Peptides For Intestinal Epithelial Womentioning

confidence: 99%

Epithelial restitution and wound healing in inflammatory bowel disease

Sturm¹,

Dignaß²

2008

WJG

283

260

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disorders including inflammatory bowel diseases and require constant repair of the epithelium. Enhancement of intestinal repair mechanisms by regulatory peptides or other modulatory factors may provide future approaches for the treatment of diseases that are characterized by injuries of the epithelial surface. THE MUCOSAL DEFENSE SYSTEMThe surface of the digestive tract is covered by epithelial cells that constitute an efficient physical barrier between the dietary and enteric flora pathogens found in the intestinal lumen and the individuum, but also allows an exchange between nutrients and the systemic circulation [1] . The epithelial defense mechanism can be categorized into three key components: pre-epithelial, epithelial and post-epithelial, the latter is represented by the lamina propria [2] . The pre-epithelial mucus barrier is composed of mucin associated with other proteins and lipids and forms a continuous gel into which a bicarbonate-rich fluid is secreted, maintaining a neutralizing pH at the epithelial surface. Phosphatidylcholine is the predominant surface bioactive phospholipid found within the gastrointestinal tract [3] . Intestinal epithelial cells secrete mucins and glycocalyx, which contain membrane-anchored negatively charged mucin-like glycoproteins and hydrophobic phospholipids [4] . The tight adherence of mucin to the apical surfaces of epithelia is owed to the existence of the specific complex between mucin oligosaccharides and the mucin binding protein of the apical mucosal membrane [5] . AbstractInflammatory bowel disease is characterized by a chronic inflammation of the intestinal mucosa. The mucosal epithelium of the alimentary tract constitutes a key element of the mucosal barrier to a broad spectrum of deleterious substances present within the intestinal lumen including bacterial microorganisms, various dietary factors, gastrointestinal secretory products and drugs. In addition, this mucosal barrier can be disturbed in the course of various intestinal disorders including inflammatory bowel diseases. Fortunately, the integrity of the gastrointestinal surface epithelium is rapidly reestablished even after extensive destruction. Rapid resealing of the epithelial barrier following injuries is accomplished by a process termed epithelial restitution, followed by more delayed mechanisms of epithelial wound healing including increased epithelial cell proliferation and epithelial cell differentiation. Restitution of the intestinal surface epithelium is modulated by a range of highly divergent factors among them a broad spectrum of structurally distinct regulatory peptides, variously described as growth factors or cytokines. S e ve ra l re g u l a t or y pe pt ide fac t or s ac t from t he basolateral site of the epithelial surface and enhance epithelial cell restitution through TGF-β-dependent pathways. In contrast, members of the trefoil factor family (TFF peptides) appear to stimulate epithelial restitution in conjunction with mucin glycoproteins through a TGF-β-independent mechanism from...

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Section: The Role Of Regulatory Peptides For Intestinal Epithelial Womentioning

confidence: 99%

Epithelial restitution and wound healing in inflammatory bowel disease

Sturm¹,

Dignaß²

2008

WJG

283

260

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“…DMH'nin 20 mg/kg ola rak ve ril di ği bir ça lış ma da, ilk 16 hafta bo yun ca, hay van la rın %53'ünün öl dü ğü ra por edi lir ken 16 ay nı doz ve ri len baş ka bir ça lış ma da, DMH en jek si yo nun dan son ra fark lı za man lar da 210 fa re nin 13 ta ne si nin öl dü ğü be lir til miş tir. 17 Tü mör olu şu mu na bağ lı ola rak ve DMH'nin tüm bu tok sik et ki le rin den do la yı DMH en jek te edi len hay van lar da ki lo kay bı da göz len miş tir. 18 Fa kat kon trol gru bu na gö re DMH ve ri len hay van la rın ağır lı ğın da önem li bir de ği şik lik ol ma dı ğı nı ifa de eden ça lış ma lar da bu lun mak ta dır.…”

Section: Tar Tiş Maunclassified

“…18 Fa kat kon trol gru bu na gö re DMH ve ri len hay van la rın ağır lı ğın da önem li bir de ği şik lik ol ma dı ğı nı ifa de eden ça lış ma lar da bu lun mak ta dır. 17,19,20 Ay rı ca DMH do zu nun ar tı rıl ma sıy la anal kist sık lı ğı nın art tı ğı, hay van la rın ge nel gö rün tü sü nün bo zul du ğu, rek tal pro lap sus ve kan lı ga i ta göz len diği ni gös te rir ça lış ma lar da bu lun mak ta dır. 6,17 Ça lış-ma mız da DMH'nin tok sik et ki si ne bağ lı ola rak DMH do zun dan son ra 40 hay va nın dokuz ta ne si (%22) öl dü.…”

Section: Tar Tiş Maunclassified

“…17,19,20 Ay rı ca DMH do zu nun ar tı rıl ma sıy la anal kist sık lı ğı nın art tı ğı, hay van la rın ge nel gö rün tü sü nün bo zul du ğu, rek tal pro lap sus ve kan lı ga i ta göz len diği ni gös te rir ça lış ma lar da bu lun mak ta dır. 6,17 Ça lış-ma mız da DMH'nin tok sik et ki si ne bağ lı ola rak DMH do zun dan son ra 40 hay va nın dokuz ta ne si (%22) öl dü. Ge ri ye ka lan hay van lar da ise anal ve sırt böl ge le rin de ki tüy ler de dö kün tü, tüy le rin ge nel gö rün tü sün de bo zuk luk ve kan lı ga i ta ve iki fa re de anal kist ge liş ti ği göz len di.…”

Section: Tar Tiş Maunclassified

“…Hay van la rın ta ma mın da kü çük tü mör, %96'sın da or ta bü yük lük te tü mör ve %76'sın da ise bü yük tü mör göz len miş ve lez yon la rın ge nelde dis tal ko lon da ge liş ti ği ni be lirt miş ler dir. 17 Baş -ka bir ça lış ma da top lam 34, 68 ve 136 mg/kg DMH alan hay van lar da sı ra sıy la %26, %76 ve %87 ora nın da ko lon tü mör le ri nin ge liş ti ği ve tü-mör le rin %79'unun dis tal kolo na yer leş ti ği tes pit edil miş tir. 6 Bi zim ça lış ma mız da, 20 mg/kg DMH do zun dan son ra fa re ler de %100 ko lon kan se ri geliş ti ği ve bu lez yon la rın mak ros ko pik ola rak birden faz la po lip tar zın da ol du ğu be lir len di.…”

Section: Tar Tiş Maunclassified

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Experimental Colon Tumorigenesis Induced by 1,2 Dimethylhydrazine in Balb/C Mice

Karaca¹,

Ertekın²,

Canöz³

et al. 2010

Turkiye Klinikleri J Med Sci

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o lo rek tal kar si nom, ge liş miş ül ke ler de cid di mor bi di te ve mor ta li teye yol açan önem li bir kan ser tü rü dür. Gö rül me sık lı ğı di yet ile yakın dan iliş ki li olup bu has ta lı ğın gö rül me ora nı git tik çe Turkiye Klinikleri J Med Sci 2010;30(3) 1015 1,2-Dimetilhidrazin ile Balb/C Türü Farelerde Deneysel Kolon Kanserinin İndüklenmesi ÖZET Amaç: Ko lon kan se ri dün ya da sık lık la gö rü len kan ser tür le rin den bi ri dir. Ne op las tik has talık la rın de ney sel hay van mo del le ri, in san lar da gö rü len kan ser tür le ri nin eti yo lo jik ve pa to fiz yo lojik sü reç le ri an la mak için ol duk ça önem li dir. 1,2 Di me til hid ra zin (DMH) güç lü bir ko lon kar si no je ni olup, ko lon kan se ri üze ri ne di ye tin et ki le ri ile il gi li ça lış ma lar da çok yay gın ola rak kul la nıl mış tır. Bu ça lış ma nın ama cı, ko lon da tü mör ge li şi mi ile DMH ara sın da ki iliş ki yi araş tır mak tır. Ge reç ve Yön tem ler: Araş tır ma da sekiz haf ta lık 50 adet Balb/c tü rü er kek fa re kul la nıl dı. On iki haf ta bo yunca fa re le re haf ta bir kez, sub ku tan yol dan DMH (20 mg/kg) en jek si yo nu ya pıl dı. De ney so nun da fare ler, son DMH en jek si yon dan altı haf ta son ra (A gru bu), 12 haf ta son ra (B gru bu), 18 haf ta son ra (C gru bu) ve son ola rak 24 haf ta son ra (D gru bu) sak ri fi ye edil di. Bul gu lar: A gru bun da ki fa re ler de tü mör ge liş me di. B gru bun da ki fa re le rin %71.4'ün de, C ve D gru bun da ki fa re le rin ise hep sin de tü -mör ge liş ti. Ça lış ma so nu cun da, grup B'de ge li şen top lam 36 lez yo nun %33'ünün, grup C'de top lam 59 lez yo nun %50'si nin ve grup D'de ise top lam 67 lez yo nun %34'ünün ade no kar si nom ol du ğu tespit edil di. Lez yon la rın ko lon da da ğı lı mı na ba kıl dı ğın da ise hem disp las tik lez yon la rın hem de adeno kar si nom la rın da ha çok dis tal ko lon da ge liş ti ği göz len di. So nuç: So nuç ola rak, DMH'nin tek rar la nan doz la rı so nu cun da, fa re ler de uzun bir ses siz lik dö ne min den son ra ko lo nik tü mör le rin ge liş ti ği ni göz lem le dik.Anah tar Ke li me ler: 1,2-Di me til hid ra zin; ko lon tü mör le ri; tü mör ler, de ney sel ABS TRACT Ob jec ti ve: Co lon can cer is one of the most com mon forms of can cer in the world. Expe ri men tal ani mal mo dels of the ne op las tic di se a ses are im por tant in un ders tan ding eti o lo gi cal and pat hoph ysi o lo gi cal pro ces ses. 1,2-di methyl hydra zi ne (DMH) is a po tent co lon car ci no gen and commonly used in the stu di es investigating the ef fects of di et on co lon can cer. In this study, the re la tions hip bet we en 1,2-di methyl hydra zi ne and tu mor de ve lop ment we re in ves ti ga ted. Ma te ri al and Met hods: Eight-we ek old, fifty balb/c ma le mi ce we re used for our ex pe ri ments and tre a ted with sub cu ta ne o us DMH so lu ti on (20 mg/kg) on ce we ekly thro ug ho ut a pe ri od of 12 we eks. Af ter the end of the last DMH in jec ti on, they we re sac ri fi ced in sixth (gro up A), twelfth (gro up B), eigh ...

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Glucagon‐like Peptide‐2 and the Regulation of Intestinal Growth and Function

Brubaker

2018

Comprehensive Physiology

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Glucagon-like peptide-2 (GLP-2) is an intestinally derived hormone that enhances intestinal growth, digestion, absorption, barrier function, and blood flow in healthy animals as well as preventing damage and improving repair in preclinical models of enteritis and colitis and following massive small bowel resection. These beneficial effects of GLP-2 on the intestinal tract are largely recapitulated in humans with intestinal failure. The high-specificity of this peptide for the intestinal tract and the development of degradation-resistant, long-acting GLP-2 receptor agonists have rapidly led to clinical implementation of GLP-2-based therapy for the treatment of patients with short bowel syndrome, with few reported side effects. This comprehensive review covers the biology of GLP-2, from the control of proglucagon gene expression and the posttranslational processing of proglucagon to liberate GLP-2 to the regulation of GLP-2 secretion from the intestinal L cell, and from the mechanism of action of GLP-2 through its highly localized receptor to the biological activities of GLP-2 in the intestine and other restricted locations in the body, under physiological conditions as well as in animal models of intestinal disease and in patients with short bowel syndrome. Collectively, the history of GLP-2 serves as a remarkable bench-to-bedside story of translational medicine. © 2017 American Physiological Society. Compr Physiol 8:1185-1210, 2018.

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Glucagon-like peptide 2 (GLP-2) accelerates the growth of colonic neoplasms in mice

Cited by 101 publications

References 28 publications

Epithelial restitution and wound healing in inflammatory bowel disease

Epithelial restitution and wound healing in inflammatory bowel disease

Experimental Colon Tumorigenesis Induced by 1,2 Dimethylhydrazine in Balb/C Mice

Glucagon‐like Peptide‐2 and the Regulation of Intestinal Growth and Function

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