Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice
Glucagon-like peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of glucagon-like peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes. The potent g...
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| Veröffentlicht in: | Diabetologia 2002-09, Vol.45 (9), p.1263 |
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| creator | Wang, Q Brubaker, P L |
| description | Glucagon-like peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of glucagon-like peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes.
The potent glucagon-like peptide-1 analogue Exendin-4 or vehicle (control) was administered (i.p.; 1 nmol/kg) to obese 6-week old db/db mice daily for 14 days ( n=10).
By 8 weeks of age, control db/db mice developed hyperglycaemia (fasting: 10.4+/-0.5 mmol/l), hyperinsulinaemia and impaired glucose tolerance. However, Exendin-4 treatment prevented hyperglycaemia (fasting: 6.1+/-1.0 mmol/l, p |
| doi_str_mv | 10.1007/s00125-002-0828-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_journals_213842485</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>769564991</sourcerecordid><originalsourceid>FETCH-LOGICAL-p166t-43ba50048639e5a8255e3b96e7e8ced95d859f844a136087555c26b872ac32733</originalsourceid><addsrcrecordid>eNo1UEtLw0AYXESxtfoDvMjife2-8-UoolUoeFH0FnazXzVtXmY3SP-9EetpGGaYYYaQS8FvBOfZMnIupGGcS8ZBAlNHZC60mpiWcEzmvzITYN9n5CzGLedcGW1PyUxIqaU2-Zy8reqxdB9dy-pqh7THPlUBmaBpQJcabBMNWLt9pOkTaddGTLTb0FA5jwkjrVoK9Btxx7o60OCXwdOmKvGcnGxcHfHigAvy-nD_cvfI1s-rp7vbNeuFtYlp5Z3hXINVORoH0hhUPreYIZQYchPA5BvQ2gllOWTGmFJaD5l0pZKZUgty_ZfbD93XiDEV224c2qmykELBtBLMZLo6mEbfYCj6oWrcsC_-b1A_h1Jc4w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>213842485</pqid></control><display><type>article</type><title>Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Wang, Q ; Brubaker, P L</creator><creatorcontrib>Wang, Q ; Brubaker, P L</creatorcontrib><description><![CDATA[Glucagon-like peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of glucagon-like peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes.
The potent glucagon-like peptide-1 analogue Exendin-4 or vehicle (control) was administered (i.p.; 1 nmol/kg) to obese 6-week old db/db mice daily for 14 days ( n=10).
By 8 weeks of age, control db/db mice developed hyperglycaemia (fasting: 10.4+/-0.5 mmol/l), hyperinsulinaemia and impaired glucose tolerance. However, Exendin-4 treatment prevented hyperglycaemia (fasting: 6.1+/-1.0 mmol/l, p<0.01), with reduced plasma insulin concentrations ( p<0.001) and improved glucose tolerance ( p<0.05). Peripheral insulin sensitivity was not affected. However, insulin release in vivo and in vitro from the perfused pancreas was improved by Exendin-4, as were pancreatic insulin concentrations (0.54+/-0.02 vs 0.32+/-0.01 micro g/mg protein, p<0.05). These changes occurred in conjunction with increased beta-cell mass (3.01+/-0.31 vs 2.22+/-0.22 mg, p<0.05) and proliferation (BrdU(+) beta-cells: 1.08+/-0.20 vs 0.47+/-0.11%, p<0.05), as well as decreased apoptosis (Tunel (+) beta-cells: 0.37+/-0.06 vs 1.20+/-0.21%). Western blot demonstrated increased expression of Akt1 (by fivefold, p<0.01) and p44 MAP kinase (by sixfold, p<0.01), and decreased activation of caspase-3 (by 30%, p<0.05).
Our results suggest that Ex4 treatment delays the onset of diabetes in 6-8 week old db/db mice, through a mechanism involving Akt1 and expansion of the functional beta-cell mass.]]></description><identifier>ISSN: 0012-186X</identifier><identifier>EISSN: 1432-0428</identifier><identifier>DOI: 10.1007/s00125-002-0828-3</identifier><identifier>PMID: 12242459</identifier><language>eng</language><publisher>Germany: Springer Nature B.V</publisher><subject>Animals ; Apoptosis ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Cell Division - drug effects ; Diabetes Mellitus - prevention & control ; Diabetes Mellitus, Type 1 - prevention & control ; Female ; Glucagon - therapeutic use ; Glucagon-Like Peptide 1 ; Glucose Tolerance Test ; Hyperglycemia - prevention & control ; Insulin - analysis ; Islets of Langerhans - drug effects ; Islets of Langerhans - pathology ; Mice ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Peptide Fragments - therapeutic use ; Peptides - therapeutic use ; Protein Precursors - therapeutic use ; Venoms</subject><ispartof>Diabetologia, 2002-09, Vol.45 (9), p.1263</ispartof><rights>Copyright Springer-Verlag 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12242459$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Q</creatorcontrib><creatorcontrib>Brubaker, P L</creatorcontrib><title>Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice</title><title>Diabetologia</title><addtitle>Diabetologia</addtitle><description><![CDATA[Glucagon-like peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of glucagon-like peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes.
The potent glucagon-like peptide-1 analogue Exendin-4 or vehicle (control) was administered (i.p.; 1 nmol/kg) to obese 6-week old db/db mice daily for 14 days ( n=10).
By 8 weeks of age, control db/db mice developed hyperglycaemia (fasting: 10.4+/-0.5 mmol/l), hyperinsulinaemia and impaired glucose tolerance. However, Exendin-4 treatment prevented hyperglycaemia (fasting: 6.1+/-1.0 mmol/l, p<0.01), with reduced plasma insulin concentrations ( p<0.001) and improved glucose tolerance ( p<0.05). Peripheral insulin sensitivity was not affected. However, insulin release in vivo and in vitro from the perfused pancreas was improved by Exendin-4, as were pancreatic insulin concentrations (0.54+/-0.02 vs 0.32+/-0.01 micro g/mg protein, p<0.05). These changes occurred in conjunction with increased beta-cell mass (3.01+/-0.31 vs 2.22+/-0.22 mg, p<0.05) and proliferation (BrdU(+) beta-cells: 1.08+/-0.20 vs 0.47+/-0.11%, p<0.05), as well as decreased apoptosis (Tunel (+) beta-cells: 0.37+/-0.06 vs 1.20+/-0.21%). Western blot demonstrated increased expression of Akt1 (by fivefold, p<0.01) and p44 MAP kinase (by sixfold, p<0.01), and decreased activation of caspase-3 (by 30%, p<0.05).
Our results suggest that Ex4 treatment delays the onset of diabetes in 6-8 week old db/db mice, through a mechanism involving Akt1 and expansion of the functional beta-cell mass.]]></description><subject>Animals</subject><subject>Apoptosis</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Cell Division - drug effects</subject><subject>Diabetes Mellitus - prevention & control</subject><subject>Diabetes Mellitus, Type 1 - prevention & control</subject><subject>Female</subject><subject>Glucagon - therapeutic use</subject><subject>Glucagon-Like Peptide 1</subject><subject>Glucose Tolerance Test</subject><subject>Hyperglycemia - prevention & control</subject><subject>Insulin - analysis</subject><subject>Islets of Langerhans - drug effects</subject><subject>Islets of Langerhans - pathology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred Strains</subject><subject>Peptide Fragments - therapeutic use</subject><subject>Peptides - therapeutic use</subject><subject>Protein Precursors - therapeutic use</subject><subject>Venoms</subject><issn>0012-186X</issn><issn>1432-0428</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNo1UEtLw0AYXESxtfoDvMjife2-8-UoolUoeFH0FnazXzVtXmY3SP-9EetpGGaYYYaQS8FvBOfZMnIupGGcS8ZBAlNHZC60mpiWcEzmvzITYN9n5CzGLedcGW1PyUxIqaU2-Zy8reqxdB9dy-pqh7THPlUBmaBpQJcabBMNWLt9pOkTaddGTLTb0FA5jwkjrVoK9Btxx7o60OCXwdOmKvGcnGxcHfHigAvy-nD_cvfI1s-rp7vbNeuFtYlp5Z3hXINVORoH0hhUPreYIZQYchPA5BvQ2gllOWTGmFJaD5l0pZKZUgty_ZfbD93XiDEV224c2qmykELBtBLMZLo6mEbfYCj6oWrcsC_-b1A_h1Jc4w</recordid><startdate>200209</startdate><enddate>200209</enddate><creator>Wang, Q</creator><creator>Brubaker, P L</creator><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>200209</creationdate><title>Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice</title><author>Wang, Q ; Brubaker, P L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p166t-43ba50048639e5a8255e3b96e7e8ced95d859f844a136087555c26b872ac32733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Apoptosis</topic><topic>Blood Glucose - drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Cell Division - drug effects</topic><topic>Diabetes Mellitus - prevention & control</topic><topic>Diabetes Mellitus, Type 1 - prevention & control</topic><topic>Female</topic><topic>Glucagon - therapeutic use</topic><topic>Glucagon-Like Peptide 1</topic><topic>Glucose Tolerance Test</topic><topic>Hyperglycemia - prevention & control</topic><topic>Insulin - analysis</topic><topic>Islets of Langerhans - drug effects</topic><topic>Islets of Langerhans - pathology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred Strains</topic><topic>Peptide Fragments - therapeutic use</topic><topic>Peptides - therapeutic use</topic><topic>Protein Precursors - therapeutic use</topic><topic>Venoms</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Q</creatorcontrib><creatorcontrib>Brubaker, P L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Diabetologia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Q</au><au>Brubaker, P L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice</atitle><jtitle>Diabetologia</jtitle><addtitle>Diabetologia</addtitle><date>2002-09</date><risdate>2002</risdate><volume>45</volume><issue>9</issue><spage>1263</spage><pages>1263-</pages><issn>0012-186X</issn><eissn>1432-0428</eissn><abstract><![CDATA[Glucagon-like peptide-1 ameliorates the symptoms of diabetes through stimulation of insulin secretion and enhancement of beta-cell mass. We have therefore investigated the effects of glucagon-like peptide-1 on the development of diabetes, using db/db mice as a model of Type II diabetes.
The potent glucagon-like peptide-1 analogue Exendin-4 or vehicle (control) was administered (i.p.; 1 nmol/kg) to obese 6-week old db/db mice daily for 14 days ( n=10).
By 8 weeks of age, control db/db mice developed hyperglycaemia (fasting: 10.4+/-0.5 mmol/l), hyperinsulinaemia and impaired glucose tolerance. However, Exendin-4 treatment prevented hyperglycaemia (fasting: 6.1+/-1.0 mmol/l, p<0.01), with reduced plasma insulin concentrations ( p<0.001) and improved glucose tolerance ( p<0.05). Peripheral insulin sensitivity was not affected. However, insulin release in vivo and in vitro from the perfused pancreas was improved by Exendin-4, as were pancreatic insulin concentrations (0.54+/-0.02 vs 0.32+/-0.01 micro g/mg protein, p<0.05). These changes occurred in conjunction with increased beta-cell mass (3.01+/-0.31 vs 2.22+/-0.22 mg, p<0.05) and proliferation (BrdU(+) beta-cells: 1.08+/-0.20 vs 0.47+/-0.11%, p<0.05), as well as decreased apoptosis (Tunel (+) beta-cells: 0.37+/-0.06 vs 1.20+/-0.21%). Western blot demonstrated increased expression of Akt1 (by fivefold, p<0.01) and p44 MAP kinase (by sixfold, p<0.01), and decreased activation of caspase-3 (by 30%, p<0.05).
Our results suggest that Ex4 treatment delays the onset of diabetes in 6-8 week old db/db mice, through a mechanism involving Akt1 and expansion of the functional beta-cell mass.]]></abstract><cop>Germany</cop><pub>Springer Nature B.V</pub><pmid>12242459</pmid><doi>10.1007/s00125-002-0828-3</doi></addata></record> |
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| subjects | Animals Apoptosis Blood Glucose - drug effects Blood Glucose - metabolism Cell Division - drug effects Diabetes Mellitus - prevention & control Diabetes Mellitus, Type 1 - prevention & control Female Glucagon - therapeutic use Glucagon-Like Peptide 1 Glucose Tolerance Test Hyperglycemia - prevention & control Insulin - analysis Islets of Langerhans - drug effects Islets of Langerhans - pathology Mice Mice, Inbred C57BL Mice, Inbred Strains Peptide Fragments - therapeutic use Peptides - therapeutic use Protein Precursors - therapeutic use Venoms |
| title | Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice |
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