JP5561639B2 - Gpr43陽性・腸内分泌細胞増加促進剤 - Google Patents
Gpr43陽性・腸内分泌細胞増加促進剤 Download PDFInfo
- Publication number
- JP5561639B2 JP5561639B2 JP2010078653A JP2010078653A JP5561639B2 JP 5561639 B2 JP5561639 B2 JP 5561639B2 JP 2010078653 A JP2010078653 A JP 2010078653A JP 2010078653 A JP2010078653 A JP 2010078653A JP 5561639 B2 JP5561639 B2 JP 5561639B2
- Authority
- JP
- Japan
- Prior art keywords
- gpr43
- positive
- cells
- enteroendocrine
- glp
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 102100040133 Free fatty acid receptor 2 Human genes 0.000 title claims description 68
- 210000003158 enteroendocrine cell Anatomy 0.000 title claims description 41
- 101000890668 Homo sapiens Free fatty acid receptor 2 Proteins 0.000 title claims 4
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical compound OC[C@H]1O[C@@](CO)(OC[C@@]2(OC[C@@]3(OC[C@@]4(OC[C@@]5(OC[C@@]6(OC[C@@]7(OC[C@@]8(OC[C@@]9(OC[C@@]%10(OC[C@@]%11(O[C@H]%12O[C@H](CO)[C@@H](O)[C@H](O)[C@H]%12O)O[C@H](CO)[C@@H](O)[C@@H]%11O)O[C@H](CO)[C@@H](O)[C@@H]%10O)O[C@H](CO)[C@@H](O)[C@@H]9O)O[C@H](CO)[C@@H](O)[C@@H]8O)O[C@H](CO)[C@@H](O)[C@@H]7O)O[C@H](CO)[C@@H](O)[C@@H]6O)O[C@H](CO)[C@@H](O)[C@@H]5O)O[C@H](CO)[C@@H](O)[C@@H]4O)O[C@H](CO)[C@@H](O)[C@@H]3O)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O FTSSQIKWUOOEGC-RULYVFMPSA-N 0.000 claims description 32
- 229940107187 fructooligosaccharide Drugs 0.000 claims description 23
- 230000000968 intestinal effect Effects 0.000 claims description 21
- 210000003890 endocrine cell Anatomy 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 6
- 101710142059 Free fatty acid receptor 2 Proteins 0.000 description 64
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 17
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 17
- 102100040918 Pro-glucagon Human genes 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 238000012360 testing method Methods 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 12
- 235000013305 food Nutrition 0.000 description 12
- 238000000034 method Methods 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- 210000001072 colon Anatomy 0.000 description 8
- 210000001035 gastrointestinal tract Anatomy 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 235000021391 short chain fatty acids Nutrition 0.000 description 7
- 150000004666 short chain fatty acids Chemical class 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical class OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 6
- 210000003405 ileum Anatomy 0.000 description 6
- 230000001737 promoting effect Effects 0.000 description 6
- YNXLOPYTAAFMTN-SBUIBGKBSA-N C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 Chemical compound C([C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)C1=CC=C(O)C=C1 YNXLOPYTAAFMTN-SBUIBGKBSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 102100029909 Peptide YY Human genes 0.000 description 5
- 108010088847 Peptide YY Proteins 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 210000002429 large intestine Anatomy 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000035790 physiological processes and functions Effects 0.000 description 5
- 241000186000 Bifidobacterium Species 0.000 description 4
- 210000004921 distal colon Anatomy 0.000 description 4
- 238000012744 immunostaining Methods 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 102100040136 Free fatty acid receptor 3 Human genes 0.000 description 3
- 101710142057 Free fatty acid receptor 3 Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229920004890 Triton X-100 Polymers 0.000 description 3
- 239000013504 Triton X-100 Substances 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 238000009395 breeding Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000002919 epithelial cell Anatomy 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000000834 fixative Substances 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- -1 OCT compound Chemical class 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000012137 double-staining Methods 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002055 immunohistochemical effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000009456 molecular mechanism Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000003307 slaughter Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- VAWYEUIPHLMNNF-OESPXIITSA-N 1-kestose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 VAWYEUIPHLMNNF-OESPXIITSA-N 0.000 description 1
- GIUOHBJZYJAZNP-DVZCMHTBSA-N 1-kestose Natural products OC[C@@H]1O[C@](CO)(OC[C@]2(O[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)O[C@@H](O)[C@@H](O)[C@@H]2O)[C@@H](O)[C@@H]1O GIUOHBJZYJAZNP-DVZCMHTBSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 101150008543 Ffar3 gene Proteins 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000051325 Glucagon Human genes 0.000 description 1
- 108060003199 Glucagon Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- 206010029719 Nonspecific reaction Diseases 0.000 description 1
- FLDFNEBHEXLZRX-DLQNOBSRSA-N Nystose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(O[C@@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FLDFNEBHEXLZRX-DLQNOBSRSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 238000004378 air conditioning Methods 0.000 description 1
- GZCGUPFRVQAUEE-VANKVMQKSA-N aldehydo-L-glucose Chemical compound OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)C=O GZCGUPFRVQAUEE-VANKVMQKSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
- 235000021240 caseins Nutrition 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- BJHIKXHVCXFQLS-UYFOZJQFSA-N fructose group Chemical group OCC(=O)[C@@H](O)[C@H](O)[C@H](O)CO BJHIKXHVCXFQLS-UYFOZJQFSA-N 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000003629 gastrointestinal hormone Substances 0.000 description 1
- 230000005176 gastrointestinal motility Effects 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 230000001744 histochemical effect Effects 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000005965 immune activity Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000007901 in situ hybridization Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- VAWYEUIPHLMNNF-UHFFFAOYSA-N kestotriose Natural products OC1C(O)C(CO)OC1(CO)OCC1(OC2C(C(O)C(O)C(CO)O2)O)C(O)C(O)C(CO)O1 VAWYEUIPHLMNNF-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- 235000012054 meals Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 239000012120 mounting media Substances 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 230000003880 negative regulation of appetite Effects 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- FLDFNEBHEXLZRX-UHFFFAOYSA-N nystose Natural products OC1C(O)C(CO)OC1(CO)OCC1(OCC2(OC3C(C(O)C(O)C(CO)O3)O)C(C(O)C(CO)O2)O)C(O)C(O)C(CO)O1 FLDFNEBHEXLZRX-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000010517 secondary reaction Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 150000004044 tetrasaccharides Chemical class 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Images
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Non-Alcoholic Beverages (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
[材料及び方法]
本試験にはフラクトオリゴ糖としてメイオリゴP粉末(フラクトオリゴ糖含量95.4%、明治製菓株式会社製)を使用した。
2.供試動物
日本エスエルシー株式会社生産の雄性Slc:Wistarラット(SPF)9週齢を10匹購入した。動物は購入から実験開始まで馴化した。
3.飼育施設
動物は温度24±2℃、湿度50±10%、空調方式:オールフレッシュエアー、午前7時から午後7時までの12時間照明に設定されたバリア施設内の動物室で飼育した。
4.飼育方法
試験期間中はアルミ製平板ケージ(W25×D40×H18cm)で個別飼育した。動物には3日間の予備飼育期間中は固形飼料(ラボMRストック日本農産工業株式会社)を、群分け後は、試験期間を通じ特殊混餌粉末飼料(オリエンタル酵母工業株式会社にて作製)を16g/日摂取させた。飲水は、水道水を給水瓶で、試験期間を通じ自由摂取させた。
5−1.特殊混餌粉末飼料の調製方法
放射線滅菌した、表1に示した配合の2種類の特殊混餌粉末飼料をオリエンタル酵母工業株式会社にて作製した。
5−2.測定及び群分け方法
9週齢のラットの体重を測定し、これを指標とし、層別連続無作為化法により対照群と5%FOS群とに群分けを行った。それぞれの群のラットに、表1に示す混餌粉末飼料を28日間にわたり、1日あたり16g給与し、食べ残した場合には残量を測定した。投与期間中、2回/週の割合で体重測定を行った。
6−1.屠殺・腸管摘出
ラットをジエチルエーテルにより吸入麻酔し、断頭・放血屠殺した。回腸以下を摘出して氷冷リン酸緩衝液(PBS)+ニカルジピン(10−6M)に浸漬した。
6−2.標本組織の区分
本試験に供する腸管組織は、回腸終末部(回盲部より口側へ約2cmまで)と、近位結腸と、遠位結腸とに区分した。
7−1.Zamboni(ザンボニ)固定液の調製
4%パラホルムアルデヒド、0.2%ピクリン酸、及び0.1Mリン酸緩衝液(pH7.4)を含むZamboni固定液を用時調製した。
腸管組織各部位を組織包埋カセット(プロカセット、サクラファインテックジャパン株式会社、日本)に入れ、Zamboni固定液20時間、4℃で浸漬固定した。固定した組織をPBSで10分×3回洗浄し、さらにPBSを毎日交換しながら3日間4℃で保存した。次に、10%→20%→30%ショ糖PBSに2時間ずつ浸潤させてクリオプロテクションを行った。標本をOCTコンパウンド(サクラファインテックジャパン株式会社)に包埋、液体窒素で凍結、凍結ブロックは切片作製まで−80℃で保存した。凍結した組織をクリオスタット(CM1100、Leica Microsystems、ドイツ)で10μm厚に薄切し、PLL(Poly−L−Lysine)被覆したスライドグラスに切片を貼り付け、風乾、染色に供するまで−80℃で保存した。なお、組織染色・計測を行う実験者とは別の実験者をコントローラーとして標本ラベルをコード化し、盲検的に以下の試験を行った。
7−3.蛍光免疫染色
免疫染色によりGPR43陽性・腸内分泌細胞及びGLP−1陽性・腸内分泌細胞の細胞密度について、それぞれ2切片以上の標本から各切片5視野以上を計測し、動物1個体1部位、10視野以上の計測結果を平均して1標本のデータ(n=1)とした。各食餌群n=5の平均を算出し、t‐検定によって対照群と5%FOS群との間の有意差検定(有意水準5%未満)を行った。
1.飼育データ
1−1.一般状態観察
被験物質食餌飼育期間中、全ての動物の一般状態に異常はなく、被験物質摂取による下痢及び軟便等も観察されなかった。
1−2.体重
体重推移を図1に示した。対照群と5%FOS群間の体重増加に有意な差はみられなかった。
1−3.残餌量
特餌開始14日まではいずれの試験群も混餌飼料を残す動物はほとんどいなかった。しかし、5%FOS群では、23日以降3匹に食べ残しがみられたが、食べ残した量は少量(4g以内)であった。
2−1.GPR−43陽性・腸内分泌細胞数
ウサギ抗GPR43(RY1505)を用いた蛍光免疫染色により、GPR43免疫活性を有する腸内分泌細胞が観察された。5%FOS群の単位面積(1mm2)当たりのGPR43陽性・腸内分泌細胞数は、対照群に対して、回腸終末部で1.42倍、近位結腸で3.33倍、遠位結腸で1.42倍に増加しており、近位結腸においては統計学的に有意に増加していた(P<0.05)。なお、腸内分泌細胞のほか粘膜における上皮細胞もGPR43を発現するとされるが、今回の実験では粘膜厚(上皮細胞数に相当する)に変化が認められなかったため、増加したのは腸内分泌細胞のみであったと示唆された。
抗GLP−1抗体を用いた蛍光免疫染色により、GLP−1免疫活性を有する腸内分泌細胞が観察された。回腸終末部及び遠位結腸にはウサギ抗GLP−1抗体(Y320)、近位結腸にはヤギ抗GLP−1抗体(sc7782)をそれぞれ用いた。5%FOS群の単位面積(1mm2)当たりのGLP−1陽性・腸内分泌細胞数は、対照群に対して、回腸終末部で1.28倍、近位結腸で2.08倍、遠位結腸で1.25倍に増加しており、近位結腸においては統計学的に有意に増加していた(P<0.001)。
本実施例において、5%FOS群は、対照群に比して体重増加に差は無く、下痢等も発生しなかったことから、5%FOS食餌による不快な症状は惹起されなかったものと考えられる。また、粘膜の肥厚等の形態的変化も観察されなかったが、単位面積当たりのGPR43陽性・腸内分泌細胞及びGLP−1陽性・腸内分泌細胞数は、近位結腸においてそれぞれ約3倍及び約2倍に有意に増加し、遠位結腸、回腸終末部においても増加傾向を示した。また、二重染色試験により、GPR43及びGLP−1が殆ど同じ細胞に共存することが示されたことから、増加したGPR43陽性・腸内分泌細胞は殆どL型腸内分泌細胞であると示唆された。
以下に示す配合比率で定法に従い300mgの錠剤を製造した。
メイオリゴP粉末
(フラクトオリゴ糖含量95.4%、明治製菓株式会社製) 250mg
トウモロコシデンプン 15mg
結晶セルロース 25mg
カルボキシメチルセルロース 10mg
以下に示す配合比率で定法に従い散剤を製造した。
メイオリゴP粉末
(フラクトオリゴ糖含量95.4%、明治製菓株式会社製) 200mg
乳糖 791mg
ヒドロキシプロピルセルロース 4mg
無水ケイ酸 5mg
以下に示す配合比率で定法に従い錠菓を製造した。
メイオリゴP粉末
(フラクトオリゴ糖含量95.4%、明治製菓株式会社製) 85mg
アビセル 4mg
クエン酸 3mg
シュガーエステル 3mg
ビフィズス菌 5mg
Claims (2)
- フラクトオリゴ糖を有効成分として含有する、GPR43陽性・腸内分泌細胞増加促進剤。
- 前記GPR43陽性・腸内分泌細胞がL型腸内分泌細胞である、請求項1記載のGPR43陽性・腸内分泌細胞増加促進剤。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010078653A JP5561639B2 (ja) | 2010-03-30 | 2010-03-30 | Gpr43陽性・腸内分泌細胞増加促進剤 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2010078653A JP5561639B2 (ja) | 2010-03-30 | 2010-03-30 | Gpr43陽性・腸内分泌細胞増加促進剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2011207834A JP2011207834A (ja) | 2011-10-20 |
JP5561639B2 true JP5561639B2 (ja) | 2014-07-30 |
Family
ID=44939282
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2010078653A Active JP5561639B2 (ja) | 2010-03-30 | 2010-03-30 | Gpr43陽性・腸内分泌細胞増加促進剤 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JP5561639B2 (ja) |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003201239A (ja) * | 2001-11-05 | 2003-07-18 | Meiji Milk Prod Co Ltd | 免疫賦活食品組成物 |
US8927504B2 (en) * | 2007-04-03 | 2015-01-06 | Mitsubishi Tanabe Pharma Corporation | Combined use of dipeptidyl peptidase 4 inhibitor and sweetener |
-
2010
- 2010-03-30 JP JP2010078653A patent/JP5561639B2/ja active Active
Also Published As
Publication number | Publication date |
---|---|
JP2011207834A (ja) | 2011-10-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Tang et al. | Effects of Bacillus subtilis DSM32315 supplementation and dietary crude protein level on performance, gut barrier function and microbiota profile in weaned piglets | |
Yang et al. | Effect of Lactobacillus plantarum on diarrhea and intestinal barrier function of young piglets challenged with enterotoxigenic Escherichia coli K88 | |
Nyachoti et al. | Weaned pig responses to Escherichia coli K88 oral challenge when receiving a lysozyme supplement | |
Yang et al. | Effect of chito-oligosaccharide on growth performance, intestinal barrier function, intestinal morphology and cecal microflora in weaned pigs | |
Guilloteau et al. | From the gut to the peripheral tissues: the multiple effects of butyrate | |
Moran et al. | Sweet taste receptor expression in ruminant intestine and its activation by artificial sweeteners to regulate glucose absorption | |
Kempf et al. | What do we know about resistance to colistin in Enterobacteriaceae in avian and pig production in Europe? | |
Gao et al. | Effects of spray-dried animal plasma on serous and intestinal redox status and cytokines of neonatal piglets | |
Waldron et al. | Effect of lipopolysaccharide on indices of peripheral and hepatic metabolism in lactating cows | |
Spaeth et al. | Bulk prevents bacterial translocation induced by the oral administration of total parenteral nutrition solution | |
Dyer et al. | Adaptive response of equine intestinal Na+/glucose co-transporter (SGLT1) to an increase in dietary soluble carbohydrate | |
Taylor-Edwards et al. | Glucagon-like peptide-2 (GLP-2) increases small intestinal blood flow and mucosal growth in ruminating calves | |
Saqui-Salces et al. | Modulation of intestinal cell differentiation in growing pigs is dependent on the fiber source in the diet | |
Hansen et al. | Diets containing inulin but not lupins help to prevent swine dysentery in experimentally challenged pigs | |
Wilson et al. | Supplemental butyrate does not enhance the absorptive or barrier functions of the isolated ovine ruminal epithelia | |
KR20070062945A (ko) | 고분자량의 peg-유사 화합물을 포함하는 치료학적수송 시스템 | |
Sun et al. | The effects of subacute ruminal acidosis on rumen epithelium barrier function in dairy goats | |
Zhou et al. | Gut microbiota absence and transplantation affect growth and intestinal functions: an investigation in a germ-free pig model | |
Wang et al. | Epidermal growth factor promotes intestinal secretory cell differentiation in weaning piglets via Wnt/β-catenin signalling | |
Wang et al. | Comparison of the biological activities of Saccharomyces cerevisiae-expressed intracellular EGF, extracellular EGF, and tagged EGF in early-weaned pigs | |
JP2012521987A (ja) | 放射線照射誘発型上皮障害を予防および治療する方法 | |
Pisoni et al. | The effects of supplementing yeast fermentation products on gut permeability, hormone concentration, and growth in newborn dairy calves | |
Van der Marel et al. | Differences between intestinal segments and soybean meal–induced changes in intestinal mucus composition of common carp C yprinus carpio L. | |
Lee et al. | Effects of dietary protein content and crystalline amino acid supplementation patterns on growth performance, intestinal histomorphology, and immune response in weaned pigs raised under different sanitary conditions | |
Sun et al. | Ultra‐high temperature treatment and storage of infant formula induces dietary protein modifications, gut dysfunction, and inflammation in preterm pigs |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20130111 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130111 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20140225 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140424 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140520 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140530 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5561639 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |