PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice
Aims: PEGylation – covalent modification of therapeutic peptides with polyethylene glycol (PEG) – is viewed as an effective way of prolonging the short lifetime of glucagon‐like peptide‐1 (GLP‐1). In this study, we investigated the hypoglycaemic efficacies of PEGylated GLP‐1s administered intranasa...
Gespeichert in:
| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2008-04, Vol.10 (4), p.343-346 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 346 |
|---|---|
| container_issue | 4 |
| container_start_page | 343 |
| container_title | Diabetes, obesity & metabolism |
| container_volume | 10 |
| creator | Youn, Y. S. Jeon, J. E. Chae, S. Y. Lee, S. Lee, K. C. |
| description | Aims: PEGylation – covalent modification of therapeutic peptides with polyethylene glycol (PEG) – is viewed as an effective way of prolonging the short lifetime of glucagon‐like peptide‐1 (GLP‐1). In this study, we investigated the hypoglycaemic efficacies of PEGylated GLP‐1s administered intranasally in type 2 diabetic db/db mice.
Methods: Three types of site‐specific (Lys34) PEGylated GLP‐1 analogues (PEG molecular weight: 1, 2 or 5 kDa) were synthesized. Their metabolic stabilities were evaluated in nasal mucosa enzyme pools. Oral glucose tolerance test was conducted 30, 60 and 120 min after intranasally administering these analogues in type 2 diabetic db/db mice.
Results: PEGylated GLP‐1 analogues were found to have significantly longer half‐lives than native GLP‐1 in nasal mucosa enzymes (2.4‐fold to 11.0‐fold, p 51.8 ± 5.8% (p |
| doi_str_mv | 10.1111/j.1463-1326.2007.00823.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70386715</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70386715</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4703-145d6f56758d31c136b2d0d36cfe6b0d47533adccdc009d4d4e89a6e8ee7ae963</originalsourceid><addsrcrecordid>eNqNkEtP3DAURi1EBZT2LyCv2CXYcWI7EhugdIrEa9HH0nLsm8GD8yDOtJNl_3kdZkS3eGNL_s53dQ9CmJKUxnO2SmnOWUJZxtOMEJESIjOWbvbQ0dvH_us7S2RJskP0MYQVISRnUhygQyoJyyUrj9Dfx-vF5PXouha7ph-63xDw-AT4aeq7pZ-MhsYZDHXtjDYT7mrs2nHQrQ7a-wlr27jWhREGsHjp10Yvuzbx7hlwD_3oLCQ0EnicesAZtk5XMMZCW53ZCsdq-IQ-1NoH-Ly7j9GPr9ffr74ltw-Lm6uL28TkgsSV8sLyuuCikJZRQxmvMkss46YGXhGbi4IxbY2xhpDS5jYHWWoOEkBoKDk7Rqfb3rjkyxrCqBoXDHivW-jWQcUhkgtaxKDcBs3QhTBArfrBNXqYFCVq1q9WarasZstq1q9e9atNRE92M9ZVA_Y_uPMdA-fbwB_nYXp3sfrycBcfEU-2-Gx884br4VlxwUShft0vlLgksrhfcPWT_QN6LqRU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70386715</pqid></control><display><type>article</type><title>PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Youn, Y. S. ; Jeon, J. E. ; Chae, S. Y. ; Lee, S. ; Lee, K. C.</creator><creatorcontrib>Youn, Y. S. ; Jeon, J. E. ; Chae, S. Y. ; Lee, S. ; Lee, K. C.</creatorcontrib><description>Aims: PEGylation – covalent modification of therapeutic peptides with polyethylene glycol (PEG) – is viewed as an effective way of prolonging the short lifetime of glucagon‐like peptide‐1 (GLP‐1). In this study, we investigated the hypoglycaemic efficacies of PEGylated GLP‐1s administered intranasally in type 2 diabetic db/db mice.
Methods: Three types of site‐specific (Lys34) PEGylated GLP‐1 analogues (PEG molecular weight: 1, 2 or 5 kDa) were synthesized. Their metabolic stabilities were evaluated in nasal mucosa enzyme pools. Oral glucose tolerance test was conducted 30, 60 and 120 min after intranasally administering these analogues in type 2 diabetic db/db mice.
Results: PEGylated GLP‐1 analogues were found to have significantly longer half‐lives than native GLP‐1 in nasal mucosa enzymes (2.4‐fold to 11.0‐fold, p < 0.005). Non‐PEGylated GLP‐1 at 100 nmol/kg was not found to have marked efficacy irrespective of nasal administration time [total hypoglycaemic degree (HDtotal) values 2.8–17.3%]. On the contrary, PEGylated GLP‐1s (100 nmol/kg) showed obvious efficacies with maximum HDtotal values of >51.8 ± 5.8% (p < 0.005 vs. GLP‐1).
Conclusion: This study highlights the pharmacological potential of intranasally administered PEGylated GLP‐1s in terms of stabilizing postprandial hyperglycaemia in type 2 diabetic patients.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/j.1463-1326.2007.00823.x</identifier><identifier>PMID: 18034839</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Administration, Inhalation ; Animals ; Blood Glucose - analysis ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - drug therapy ; Drug Carriers ; GLP-1 ; Glucagon-Like Peptide 1 - administration & dosage ; Glucagon-Like Peptide 1 - pharmacokinetics ; Glucagon-Like Peptide 1 - therapeutic use ; Glucose Tolerance Test ; Half-Life ; hypoglycaemic efficacy ; Hypoglycemic Agents - administration & dosage ; Hypoglycemic Agents - metabolism ; Hypoglycemic Agents - therapeutic use ; Insulin - blood ; intranasal administration ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; PEGylation ; Polyethylene Glycols ; type 2 diabetes</subject><ispartof>Diabetes, obesity & metabolism, 2008-04, Vol.10 (4), p.343-346</ispartof><rights>2007 The Authors</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4703-145d6f56758d31c136b2d0d36cfe6b0d47533adccdc009d4d4e89a6e8ee7ae963</citedby><cites>FETCH-LOGICAL-c4703-145d6f56758d31c136b2d0d36cfe6b0d47533adccdc009d4d4e89a6e8ee7ae963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1463-1326.2007.00823.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1463-1326.2007.00823.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18034839$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Youn, Y. S.</creatorcontrib><creatorcontrib>Jeon, J. E.</creatorcontrib><creatorcontrib>Chae, S. Y.</creatorcontrib><creatorcontrib>Lee, S.</creatorcontrib><creatorcontrib>Lee, K. C.</creatorcontrib><title>PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>Aims: PEGylation – covalent modification of therapeutic peptides with polyethylene glycol (PEG) – is viewed as an effective way of prolonging the short lifetime of glucagon‐like peptide‐1 (GLP‐1). In this study, we investigated the hypoglycaemic efficacies of PEGylated GLP‐1s administered intranasally in type 2 diabetic db/db mice.
Methods: Three types of site‐specific (Lys34) PEGylated GLP‐1 analogues (PEG molecular weight: 1, 2 or 5 kDa) were synthesized. Their metabolic stabilities were evaluated in nasal mucosa enzyme pools. Oral glucose tolerance test was conducted 30, 60 and 120 min after intranasally administering these analogues in type 2 diabetic db/db mice.
Results: PEGylated GLP‐1 analogues were found to have significantly longer half‐lives than native GLP‐1 in nasal mucosa enzymes (2.4‐fold to 11.0‐fold, p < 0.005). Non‐PEGylated GLP‐1 at 100 nmol/kg was not found to have marked efficacy irrespective of nasal administration time [total hypoglycaemic degree (HDtotal) values 2.8–17.3%]. On the contrary, PEGylated GLP‐1s (100 nmol/kg) showed obvious efficacies with maximum HDtotal values of >51.8 ± 5.8% (p < 0.005 vs. GLP‐1).
Conclusion: This study highlights the pharmacological potential of intranasally administered PEGylated GLP‐1s in terms of stabilizing postprandial hyperglycaemia in type 2 diabetic patients.</description><subject>Administration, Inhalation</subject><subject>Animals</subject><subject>Blood Glucose - analysis</subject><subject>Diabetes Mellitus, Experimental</subject><subject>Diabetes Mellitus, Type 2 - blood</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Drug Carriers</subject><subject>GLP-1</subject><subject>Glucagon-Like Peptide 1 - administration & dosage</subject><subject>Glucagon-Like Peptide 1 - pharmacokinetics</subject><subject>Glucagon-Like Peptide 1 - therapeutic use</subject><subject>Glucose Tolerance Test</subject><subject>Half-Life</subject><subject>hypoglycaemic efficacy</subject><subject>Hypoglycemic Agents - administration & dosage</subject><subject>Hypoglycemic Agents - metabolism</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Insulin - blood</subject><subject>intranasal administration</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Mutant Strains</subject><subject>PEGylation</subject><subject>Polyethylene Glycols</subject><subject>type 2 diabetes</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtP3DAURi1EBZT2LyCv2CXYcWI7EhugdIrEa9HH0nLsm8GD8yDOtJNl_3kdZkS3eGNL_s53dQ9CmJKUxnO2SmnOWUJZxtOMEJESIjOWbvbQ0dvH_us7S2RJskP0MYQVISRnUhygQyoJyyUrj9Dfx-vF5PXouha7ph-63xDw-AT4aeq7pZ-MhsYZDHXtjDYT7mrs2nHQrQ7a-wlr27jWhREGsHjp10Yvuzbx7hlwD_3oLCQ0EnicesAZtk5XMMZCW53ZCsdq-IQ-1NoH-Ly7j9GPr9ffr74ltw-Lm6uL28TkgsSV8sLyuuCikJZRQxmvMkss46YGXhGbi4IxbY2xhpDS5jYHWWoOEkBoKDk7Rqfb3rjkyxrCqBoXDHivW-jWQcUhkgtaxKDcBs3QhTBArfrBNXqYFCVq1q9WarasZstq1q9e9atNRE92M9ZVA_Y_uPMdA-fbwB_nYXp3sfrycBcfEU-2-Gx884br4VlxwUShft0vlLgksrhfcPWT_QN6LqRU</recordid><startdate>200804</startdate><enddate>200804</enddate><creator>Youn, Y. S.</creator><creator>Jeon, J. E.</creator><creator>Chae, S. Y.</creator><creator>Lee, S.</creator><creator>Lee, K. C.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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></search><sort><creationdate>200804</creationdate><title>PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice</title><author>Youn, Y. S. ; Jeon, J. E. ; Chae, S. Y. ; Lee, S. ; Lee, K. C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4703-145d6f56758d31c136b2d0d36cfe6b0d47533adccdc009d4d4e89a6e8ee7ae963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Administration, Inhalation</topic><topic>Animals</topic><topic>Blood Glucose - analysis</topic><topic>Diabetes Mellitus, Experimental</topic><topic>Diabetes Mellitus, Type 2 - blood</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Drug Carriers</topic><topic>GLP-1</topic><topic>Glucagon-Like Peptide 1 - administration & dosage</topic><topic>Glucagon-Like Peptide 1 - pharmacokinetics</topic><topic>Glucagon-Like Peptide 1 - therapeutic use</topic><topic>Glucose Tolerance Test</topic><topic>Half-Life</topic><topic>hypoglycaemic efficacy</topic><topic>Hypoglycemic Agents - administration & dosage</topic><topic>Hypoglycemic Agents - metabolism</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Insulin - blood</topic><topic>intranasal administration</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Mutant Strains</topic><topic>PEGylation</topic><topic>Polyethylene Glycols</topic><topic>type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Youn, Y. S.</creatorcontrib><creatorcontrib>Jeon, J. E.</creatorcontrib><creatorcontrib>Chae, S. Y.</creatorcontrib><creatorcontrib>Lee, S.</creatorcontrib><creatorcontrib>Lee, K. C.</creatorcontrib><collection>Istex</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><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Youn, Y. S.</au><au>Jeon, J. E.</au><au>Chae, S. Y.</au><au>Lee, S.</au><au>Lee, K. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2008-04</date><risdate>2008</risdate><volume>10</volume><issue>4</issue><spage>343</spage><epage>346</epage><pages>343-346</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>Aims: PEGylation – covalent modification of therapeutic peptides with polyethylene glycol (PEG) – is viewed as an effective way of prolonging the short lifetime of glucagon‐like peptide‐1 (GLP‐1). In this study, we investigated the hypoglycaemic efficacies of PEGylated GLP‐1s administered intranasally in type 2 diabetic db/db mice.
Methods: Three types of site‐specific (Lys34) PEGylated GLP‐1 analogues (PEG molecular weight: 1, 2 or 5 kDa) were synthesized. Their metabolic stabilities were evaluated in nasal mucosa enzyme pools. Oral glucose tolerance test was conducted 30, 60 and 120 min after intranasally administering these analogues in type 2 diabetic db/db mice.
Results: PEGylated GLP‐1 analogues were found to have significantly longer half‐lives than native GLP‐1 in nasal mucosa enzymes (2.4‐fold to 11.0‐fold, p < 0.005). Non‐PEGylated GLP‐1 at 100 nmol/kg was not found to have marked efficacy irrespective of nasal administration time [total hypoglycaemic degree (HDtotal) values 2.8–17.3%]. On the contrary, PEGylated GLP‐1s (100 nmol/kg) showed obvious efficacies with maximum HDtotal values of >51.8 ± 5.8% (p < 0.005 vs. GLP‐1).
Conclusion: This study highlights the pharmacological potential of intranasally administered PEGylated GLP‐1s in terms of stabilizing postprandial hyperglycaemia in type 2 diabetic patients.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>18034839</pmid><doi>10.1111/j.1463-1326.2007.00823.x</doi><tpages>4</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1462-8902 |
| ispartof | Diabetes, obesity & metabolism, 2008-04, Vol.10 (4), p.343-346 |
| issn | 1462-8902 1463-1326 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70386715 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Administration, Inhalation Animals Blood Glucose - analysis Diabetes Mellitus, Experimental Diabetes Mellitus, Type 2 - blood Diabetes Mellitus, Type 2 - drug therapy Drug Carriers GLP-1 Glucagon-Like Peptide 1 - administration & dosage Glucagon-Like Peptide 1 - pharmacokinetics Glucagon-Like Peptide 1 - therapeutic use Glucose Tolerance Test Half-Life hypoglycaemic efficacy Hypoglycemic Agents - administration & dosage Hypoglycemic Agents - metabolism Hypoglycemic Agents - therapeutic use Insulin - blood intranasal administration Male Mice Mice, Inbred C57BL Mice, Mutant Strains PEGylation Polyethylene Glycols type 2 diabetes |
| title | PEGylation improves the hypoglycaemic efficacy of intranasally administered glucagon-like peptide-1 in type 2 diabetic db/db mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T00%3A11%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PEGylation%20improves%20the%20hypoglycaemic%20efficacy%20of%20intranasally%20administered%20glucagon-like%20peptide-1%20in%20type%202%20diabetic%20db/db%20mice&rft.jtitle=Diabetes,%20obesity%20&%20metabolism&rft.au=Youn,%20Y.%20S.&rft.date=2008-04&rft.volume=10&rft.issue=4&rft.spage=343&rft.epage=346&rft.pages=343-346&rft.issn=1462-8902&rft.eissn=1463-1326&rft_id=info:doi/10.1111/j.1463-1326.2007.00823.x&rft_dat=%3Cproquest_cross%3E70386715%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70386715&rft_id=info:pmid/18034839&rfr_iscdi=true |