Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro
Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 （GHRP-6）, increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghre...
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| description | Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 （GHRP-6）, increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.
Methods A diabetic guinea pig model was produced by intraperitoneal （i.p.） injection of streptozotocin （STZ, 280 mg/kg）. Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 （10-100 μg/kg）, and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor （GHS-R） antagonist, D-Lys^3-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 （100 μg/kg） was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 （0.01-10 μmol/L） on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction （RT-PCR）.
Results We established a guinea pig model of delayed gastric emptying. Ghrelin （20, 50, or 100 μg/kg） and GHRP-6 （20, 50, or 100 μg/kg） accelerated gastric emptying in diabetic guinea pigs with gastroparesis （n=6, P 〈0.05）. In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 （100 μg/kg） failed to accelerate gastric emptying （n=6, P 〈0.05）. D-Lys^3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist （n=6, P 〈0.05）. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs （n=6, P〈0.05）. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.
Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system. |
| doi_str_mv | 10.1097/00029330-200807010-00007 |
| format | Article |
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Methods A diabetic guinea pig model was produced by intraperitoneal （i.p.） injection of streptozotocin （STZ, 280 mg/kg）. Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 （10-100 μg/kg）, and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor （GHS-R） antagonist, D-Lys^3-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 （100 μg/kg） was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 （0.01-10 μmol/L） on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction （RT-PCR）.
Results We established a guinea pig model of delayed gastric emptying. Ghrelin （20, 50, or 100 μg/kg） and GHRP-6 （20, 50, or 100 μg/kg） accelerated gastric emptying in diabetic guinea pigs with gastroparesis （n=6, P 〈0.05）. In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 （100 μg/kg） failed to accelerate gastric emptying （n=6, P 〈0.05）. D-Lys^3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist （n=6, P 〈0.05）. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs （n=6, P〈0.05）. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.
Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.</description><identifier>ISSN: 0366-6999</identifier><identifier>EISSN: 2542-5641</identifier><identifier>DOI: 10.1097/00029330-200807010-00007</identifier><identifier>PMID: 18710636</identifier><language>eng</language><publisher>China: Department of General Surgery,Sixth Hospital Affiliated to Shanghai Jiao Tong University,Shanghai 200233,China</publisher><subject>Animals ; Diabetes Mellitus, Experimental - complications ; Female ; Gastric Emptying - drug effects ; Gastroparesis - drug therapy ; Gastroparesis - physiopathology ; Ghrelin - therapeutic use ; Guinea Pigs ; In Vitro Techniques ; Male ; Muscle Contraction - drug effects ; Oligopeptides - therapeutic use ; Receptors, Ghrelin - analysis ; Streptozocin ; 平滑肌 ; 生长激素促分泌素受体 ; 生长激素释放肽6 ; 胃排空</subject><ispartof>Chinese medical journal, 2008-07, Vol.121 (13), p.1183-1188</ispartof><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-d7323d8b62d5531da7338d4ced9d5eb344d853e067a706b97baa6e19c13576603</citedby><cites>FETCH-LOGICAL-c421t-d7323d8b62d5531da7338d4ced9d5eb344d853e067a706b97baa6e19c13576603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85656X/85656X.jpg</thumbnail><link.rule.ids>314,777,781,861,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18710636$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qiu, Wen-cai</creatorcontrib><creatorcontrib>Wang, Zhi-gang</creatorcontrib><creatorcontrib>Wang, Wei-gang</creatorcontrib><creatorcontrib>Yan, Jun</creatorcontrib><creatorcontrib>Zheng, Qi</creatorcontrib><title>Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro</title><title>Chinese medical journal</title><addtitle>Chinese Medical Journal</addtitle><description>Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 （GHRP-6）, increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.
Methods A diabetic guinea pig model was produced by intraperitoneal （i.p.） injection of streptozotocin （STZ, 280 mg/kg）. Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 （10-100 μg/kg）, and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor （GHS-R） antagonist, D-Lys^3-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 （100 μg/kg） was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 （0.01-10 μmol/L） on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction （RT-PCR）.
Results We established a guinea pig model of delayed gastric emptying. Ghrelin （20, 50, or 100 μg/kg） and GHRP-6 （20, 50, or 100 μg/kg） accelerated gastric emptying in diabetic guinea pigs with gastroparesis （n=6, P 〈0.05）. In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 （100 μg/kg） failed to accelerate gastric emptying （n=6, P 〈0.05）. D-Lys^3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist （n=6, P 〈0.05）. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs （n=6, P〈0.05）. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.
Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.</description><subject>Animals</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Female</subject><subject>Gastric Emptying - drug effects</subject><subject>Gastroparesis - drug therapy</subject><subject>Gastroparesis - physiopathology</subject><subject>Ghrelin - therapeutic use</subject><subject>Guinea Pigs</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Muscle Contraction - drug effects</subject><subject>Oligopeptides - therapeutic use</subject><subject>Receptors, Ghrelin - analysis</subject><subject>Streptozocin</subject><subject>平滑肌</subject><subject>生长激素促分泌素受体</subject><subject>生长激素释放肽6</subject><subject>胃排空</subject><issn>0366-6999</issn><issn>2542-5641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkctu3CAUhlHUKpmmfYUKddGdWzAYzLKKepMidZOuEYZjm6kNDtiJmkfJ04aZTJsVl_NfpPMhhCn5RImSnwkhtWKMVDUhLZGEkqp8EXmGdnXD66oRnL5CO8KEqIRS6gK9yXlfTE0jxTm6oK2kRDCxQ483IySzwLZ6i6Hvwa4Zxx4PY4LJB2yCw0OK9-uIx5jmGACXAZjsw4AXWFbvAAscAx5MXlNcTILsMy7W8izz-BDXaH2ofHCbBYedNx0c2obNBzB48cNRfufv4rHueC9Rb9Hr3kwZ3p3OS_T729ebqx_V9a_vP6--XFeW13StnGQ1c20natc0jDojGWsdL1XKNdAxzl3bMCBCGklEp2RnjACqLGVlGYKwS_TxOffehN6EQe_jlkJp1A-jnfeHFVNWlvsiXFK83SCvevbZwjSZAHHLWijOqWh5EbbPQptizgl6vSQ_m_RXU6IPAPU_gPo_QH0EWKzvTx1bN4N7MZ6IFcGHU_YYw3BbMOjO2D-9n0DXsiSpmrEnLOej-g</recordid><startdate>20080705</startdate><enddate>20080705</enddate><creator>Qiu, Wen-cai</creator><creator>Wang, Zhi-gang</creator><creator>Wang, Wei-gang</creator><creator>Yan, Jun</creator><creator>Zheng, Qi</creator><general>Department of General Surgery,Sixth Hospital Affiliated to Shanghai Jiao Tong University,Shanghai 200233,China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>20080705</creationdate><title>Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro</title><author>Qiu, Wen-cai ; Wang, Zhi-gang ; Wang, Wei-gang ; Yan, Jun ; Zheng, Qi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-d7323d8b62d5531da7338d4ced9d5eb344d853e067a706b97baa6e19c13576603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Female</topic><topic>Gastric Emptying - drug effects</topic><topic>Gastroparesis - drug therapy</topic><topic>Gastroparesis - physiopathology</topic><topic>Ghrelin - therapeutic use</topic><topic>Guinea Pigs</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Muscle Contraction - drug effects</topic><topic>Oligopeptides - therapeutic use</topic><topic>Receptors, Ghrelin - analysis</topic><topic>Streptozocin</topic><topic>平滑肌</topic><topic>生长激素促分泌素受体</topic><topic>生长激素释放肽6</topic><topic>胃排空</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qiu, Wen-cai</creatorcontrib><creatorcontrib>Wang, Zhi-gang</creatorcontrib><creatorcontrib>Wang, Wei-gang</creatorcontrib><creatorcontrib>Yan, Jun</creatorcontrib><creatorcontrib>Zheng, Qi</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese medical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qiu, Wen-cai</au><au>Wang, Zhi-gang</au><au>Wang, Wei-gang</au><au>Yan, Jun</au><au>Zheng, Qi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro</atitle><jtitle>Chinese medical journal</jtitle><addtitle>Chinese Medical Journal</addtitle><date>2008-07-05</date><risdate>2008</risdate><volume>121</volume><issue>13</issue><spage>1183</spage><epage>1188</epage><pages>1183-1188</pages><issn>0366-6999</issn><eissn>2542-5641</eissn><abstract>Background Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In normal animals, both ghrelin and its synthetic peptide, growth hormone releasing peptide 6 （GHRP-6）, increase gastric emptying. Thus, we investigated the potential therapeutic significance of ghrelin and GHRP-6 in diabetic guinea pigs with gastric motility disorders.
Methods A diabetic guinea pig model was produced by intraperitoneal （i.p.） injection of streptozotocin （STZ, 280 mg/kg）. Diabetic guinea pigs were injected i.p. with ghrelin or GHRP-6 （10-100 μg/kg）, and the effects on gastric emptying were measured after intragastric application of phenol red. The effect of atropine or a growth hormone secretagogue receptor （GHS-R） antagonist, D-Lys^3-GHRP-6, on the gastroprokinetic effects of ghrelin or GHRP-6 （100 μg/kg） was also investigated. Further, the in vitro effects of ghrelin or GHRP-6 （0.01-10 μmol/L） on spontaneous or carbachol-induced contractile amplitude in gastric fundic circular strips taken from diabetic guinea pigs were examined. Growth hormone secretagogue receptor transcripts in the fundic strips of diabetic guinea pigs were detected by reverse transcriptase polymerase chain reaction （RT-PCR）.
Results We established a guinea pig model of delayed gastric emptying. Ghrelin （20, 50, or 100 μg/kg） and GHRP-6 （20, 50, or 100 μg/kg） accelerated gastric emptying in diabetic guinea pigs with gastroparesis （n=6, P 〈0.05）. In the presence of atropine, which delayed gastric emptying, ghrelin and GHRP-6 （100 μg/kg） failed to accelerate gastric emptying （n=6, P 〈0.05）. D-Lys^3-GHRP-6 also delayed gastric emptying induced by the GHS-R agonist （n=6, P 〈0.05）. Ghrelin and GHRP-6 increased the carbachol-induced contractile amplitude in gastric fundic strips taken from diabetic guinea pigs （n=6, P〈0.05）. RT-PCR confirmed the presence of GHS-R mRNA in the strip preparations.
Conclusions Ghrelin and GHRP-6 increased gastric emptying in diabetic guinea pigs with gastroparesis, potentially, by activating the peripheral cholinergic pathways in the enteric nervous system.</abstract><cop>China</cop><pub>Department of General Surgery,Sixth Hospital Affiliated to Shanghai Jiao Tong University,Shanghai 200233,China</pub><pmid>18710636</pmid><doi>10.1097/00029330-200807010-00007</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Diabetes Mellitus, Experimental - complications Female Gastric Emptying - drug effects Gastroparesis - drug therapy Gastroparesis - physiopathology Ghrelin - therapeutic use Guinea Pigs In Vitro Techniques Male Muscle Contraction - drug effects Oligopeptides - therapeutic use Receptors, Ghrelin - analysis Streptozocin 平滑肌 生长激素促分泌素受体 生长激素释放肽6 胃排空 |
| title | Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro |
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