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GLP-2 (rat)

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GLP-2 (rat) is an endogenous peptide that acts as an intestinal epithelium-specific growth factor. It stimulates cell proliferation and inhibits apoptosis, and also modulates intestinal glucose transport, food intake, and gastric acid secretion.

Category

Peptide Inhibitors

Catalog number

BAT-015247

CAS number

195262-56-7

Molecular Formula

C166H256N44O56S

Molecular Weight

3796.17

Specification
Reference Reading

IUPAC Name

(2S)-2-[[(2S,3R)-2-[[(2S,3S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-5-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[(2S)-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]propanoyl]amino]-3-carboxypropanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-4-methylsulfanylbutanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-3-carboxypropanoyl]amino]-3-phenylpropanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-methylpentanoyl]amino]-5-oxopentanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]butanedioic acid

Synonyms

Preproglucagon (146-178) (rat); H-His-Ala-Asp-Gly-Ser-Phe-Ser-Asp-Glu-Met-Asn-Thr-Ile-Leu-Asp-Asn-Leu-Ala-Thr-Arg-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Gln-Thr-Lys-Ile-Thr-Asp-OH; Glucagon-like Peptide 2 (rat); L-histidyl-L-alanyl-L-alpha-aspartyl-glycyl-L-seryl-L-phenylalanyl-L-seryl-L-alpha-aspartyl-L-alpha-glutamyl-L-methionyl-L-asparagyl-L-threonyl-L-isoleucyl-L-leucyl-L-alpha-aspartyl-L-asparagyl-L-leucyl-L-alanyl-L-threonyl-L-arginyl-L-alpha-aspartyl-L-phenylalanyl-L-isoleucyl-L-asparagyl-L-tryptophyl-L-leucyl-L-isoleucyl-L-glutaminyl-L-threonyl-L-lysyl-L-isoleucyl-L-threonyl-L-aspartic acid

Appearance

White Powder

Purity

≥95%

Sequence

HADGSFSDEMNTILDNLATRDFINWLIQTKITD

Storage

Store at -20°C

Solubility

Soluble in Acetic Acid

InChI

InChI=1S/C166H256N44O56S/c1-22-77(11)126(157(257)187-96(45-47-115(169)217)142(242)208-131(84(18)214)162(262)185-94(43-34-35-50-167)141(241)203-129(80(14)25-4)160(260)210-132(85(19)215)163(263)201-112(165(265)266)67-125(232)233)204-152(252)101(55-76(9)10)190-146(246)104(58-89-68-177-93-42-33-32-41-91(89)93)193-148(248)106(61-117(171)219)200-158(258)127(78(12)23-2)205-153(253)103(57-88-39-30-27-31-40-88)191-150(250)110(65-123(228)229)196-138(238)95(44-36-51-176-166(173)174)186-161(261)130(83(17)213)207-135(235)82(16)181-143(243)99(53-74(5)6)189-147(247)105(60-116(170)218)195-151(251)111(66-124(230)231)197-144(244)100(54-75(7)8)199-159(259)128(79(13)24-3)206-164(264)133(86(20)216)209-154(254)107(62-118(172)220)194-140(240)98(49-52-267-21)184-139(239)97(46-48-120(222)223)183-149(249)109(64-122(226)227)198-156(256)114(72-212)202-145(245)102(56-87-37-28-26-29-38-87)192-155(255)113(71-211)182-119(221)70-178-137(237)108(63-121(224)225)188-134(234)81(15)180-136(236)92(168)59-90-69-175-73-179-90/h26-33,37-42,68-69,73-86,92,94-114,126-133,177,211-216H,22-25,34-36,43-67,70-72,167-168H2,1-21H3,(H2,169,217)(H2,170,218)(H2,171,219)(H2,172,220)(H,175,179)(H,178,237)(H,180,236)(H,181,243)(H,182,221)(H,183,249)(H,184,239)(H,185,262)(H,186,261)(H,187,257)(H,188,234)(H,189,247)(H,190,246)(H,191,250)(H,192,255)(H,193,248)(H,194,240)(H,195,251)(H,196,238)(H,197,244)(H,198,256)(H,199,259)(H,200,258)(H,201,263)(H,202,245)(H,203,241)(H,204,252)(H,205,253)(H,206,264)(H,207,235)(H,208,242)(H,209,254)(H,210,260)(H,222,223)(H,224,225)(H,226,227)(H,228,229)(H,230,231)(H,232,233)(H,265,266)(H4,173,174,176)/t77-,78-,79-,80-,81-,82-,83+,84+,85+,86+,92-,94-,95-,96-,97-,98-,99-,100-,101-,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,126-,127-,128-,129-,130-,131-,132-,133-/m0/s1

InChI Key

JPRUMPQGPCFDGW-CWHSZFSPSA-N

Canonical SMILES

CCC(C)C(C(=O)NC(C(C)O)C(=O)NC(CC(=O)O)C(=O)O)NC(=O)C(CCCCN)NC(=O)C(C(C)O)NC(=O)C(CCC(=O)N)NC(=O)C(C(C)CC)NC(=O)C(CC(C)C)NC(=O)C(CC1=CNC2=CC=CC=C21)NC(=O)C(CC(=O)N)NC(=O)C(C(C)CC)NC(=O)C(CC3=CC=CC=C3)NC(=O)C(CC(=O)O)NC(=O)C(CCCNC(=N)N)NC(=O)C(C(C)O)NC(=O)C(C)NC(=O)C(CC(C)C)NC(=O)C(CC(=O)N)NC(=O)C(CC(=O)O)NC(=O)C(CC(C)C)NC(=O)C(C(C)CC)NC(=O)C(C(C)O)NC(=O)C(CC(=O)N)NC(=O)C(CCSC)NC(=O)C(CCC(=O)O)NC(=O)C(CC(=O)O)NC(=O)C(CO)NC(=O)C(CC4=CC=CC=C4)NC(=O)C(CO)NC(=O)CNC(=O)C(CC(=O)O)NC(=O)C(C)NC(=O)C(CC5=CNC=N5)N

1. GLP-2 decreases food intake in the dorsomedial hypothalamic nucleus (DMH) through Exendin (9-39) in male Sprague-Dawley (SD) rats

Lijun Shang, Lin Hou, Kai Meng, Huiling Sun, Jianqun Yan Physiol Behav . 2021 Feb 1;229:113253. doi: 10.1016/j.physbeh.2020.113253.

Glucagon-like peptide 2 (GLP-2), a member of Glucagon peptide family involved in regulating energy metabolism, can be produced and secreted by preproglucagonergic (PPG) neurons in the brain. GLP-2 reduces food intake but at which brain sites GLP-2 exerts its feeding-suppress effects are still unclear. In this study, we used the stereological microinjection technique and behavioral test to examine the functions of locally delivered GLP-2 into DMH on feeding behavior. We compared effects of different concentration of GLP-2 on the food intake behavior in free-feeding rats and fasted-refeeding rats. We found that GLP-2 inhibited food intake in fasted rats after a short-term intervention in a dose-dependent manner. Importantly, the effects of locally delivered GLP-2 can be blocked by specific GLP-1 receptor antagonist Exendin(9-39), but not the melanocortin-4 receptor antagonist SHU9119, indicating the involvement of specificity of GLP-2 signaling in regulating the feeding behavior. Taken together, our data revealed that GLP-2 peptide pharmacologically inhibited food intake in DMH and this effect could be blocked functionally by Exendin(9-39).

2. Is OM-3 synergistic with GLP-2 in intestinal failure?

Caitlyn M Costanzo, Marshall Z Schwartz, Avik Karmaker J Surg Res . 2017 Jan;207:7-12. doi: 10.1016/j.jss.2016.08.018.

Introduction:Glucagon-like peptide-2 (GLP-2) is a known intestinal growth factor that enhances mucosal mass and function in residual small intestine after massive small bowel resection (MSBR). Luminal omega-3 (OM-3) has been shown to have some growth factor properties. It is possible that their mechanisms of action differ. Thus, we hypothesized that administering these two substances together may have a synergistic effect.Methods:A total of 60 adult female Sprague-Dawley rats underwent 80% MSBR and divided as follows (n = 15/group): Saline (Control) + regular feeds; GLP-2 + regular feeds; Saline + OM-3 enriched feeds; and GLP-2 + OM-3 enriched feeds. Five animals per group were sacrificed at 7, 14, and 28 days. Small intestine mucosa was harvested. DNA and protein content were measured (mucosal mass markers) at all three time points. Galactose and Glycine absorption were measured (functional capacity markers) at 28 days. Statistical analysis was done by ANOVA with post hoc Tukey's HSD test.Results:At all three time points, DNA was increased in all treatment groups compared to control (P < 0.05), but GLP-2 + OM-3 group did not have increased DNA content when compared to either treatments alone. At 7 and 14 d, all three treatment groups had increased protein content compared to control (P < 0.05). At 28 d, GLP-2 + OM-3 did not have increased protein content compared to control or individual treatments (P < 1.0). All three treatment groups had increased absorption of galactose and glycine compared to control (P < 0.05) but not each other.Conclusions:Individually, GLP-2 and OM-3 are very effective in enhancing the adaptive process by increasing mucosal mass and function, at all three time points. More importantly, clinically, GLP-2 and OM-3 increase substrate absorption in a rat model of intestinal failure. However, the combination is not synergistic.

3. Dexamethasone and GLP-2 given to lactating rat dams influence glucose uptake in suckling and postweanling offspring

Zoe Todd, Alan B R Thomson, Claudiu Iordache, M Tom Clandinin, Gary Wild, Laurie Drozdowski JPEN J Parenter Enteral Nutr . 2009 Jul-Aug;33(4):433-9. doi: 10.1177/0148607108324874.

Background:Glucagon-like peptide-2 (GLP-2) enhances intestinal absorption in adult animals. Glucocorticosteroids accelerate the ontogeny of the intestine and increase sugar uptake in adult animals. Modifying the maternal diet during lactation alters nutrient uptake in the offspring. The authors hypothesized that GLP-2 and dexamethasone, when administrated to lactating rat dams, enhance sugar uptake in the suckling and postweanling offspring.Methods:Rat dams were treated during lactation with GLP-2 (0.1 microg/g/day subcutaneously [SC], twice daily), dexamethasone (0.128 microg/g/day SC, once daily), GLP-2 + dexamethasone (same doses), or placebo. The suckling offspring were sacrificed at 19-21 days of age, and the postweanlings were sacrificed 4 weeks later. Intestinal glucose and fructose uptake was assessed using an in vitro ring technique.Results:GLP-2 and dexamethasone resulted in lower body weights, and dexamethasone caused intestinal atrophy in sucklings. The jejunal atrophy in sucklings given dexamethasone was prevented by GLP-2 + dexamethasone. In sucklings, the maximal transport rate and the Michaelis affinity constant for ileal glucose uptake were both increased by GLP-2 and GLP-2 + dexamethasone. In contrast, in postweanlings, the maximal transport rate for jejunal glucose uptake was reduced by dexamethasone and GLP-2, as was ileal fructose uptake.Conclusions:Treating lactating rat dams with GLP-2 or dexamethasone enhances glucose uptake in sucklings, but the late effect is a reduction in glucose and fructose absorption in postweanlings. The nutritional significance of these findings remains to be established.