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rdf:type |
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lifeskim:mentions |
umls-concept:C0004083,
umls-concept:C0017725,
umls-concept:C0021467,
umls-concept:C0021469,
umls-concept:C0021641,
umls-concept:C0026809,
umls-concept:C0061355,
umls-concept:C0063684,
umls-concept:C0086418,
umls-concept:C0178665,
umls-concept:C0332161,
umls-concept:C0392918,
umls-concept:C0442805,
umls-concept:C0871261,
umls-concept:C1415831,
umls-concept:C1514559,
umls-concept:C1522605,
umls-concept:C1704242,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1882115,
umls-concept:C2911692
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pubmed:issue |
1-3
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pubmed:dateCreated |
2007-8-13
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pubmed:abstractText |
Inhibition of dipeptidyl peptidase-4 (DPP-4) is currently explored as a novel therapy of type 2 diabetes. The strategy has been shown to improve glycemia in most, but not all, rodent forms of glucose intolerance. In this study, we explored the effects of DPP-4 inhibition in mice with beta-cell overexpression of human islet amyloid polypeptide (IAPP). We therefore administered the orally active and highly selective DPP-4 inhibitor, vildagliptin (3 micromol/mouse daily) to female mice with beta-cell overexpression of human IAPP. Controls were given plain water, and a series of untreated wildtype mice was also included. After five weeks, an intravenous glucose tolerance test showed improved glucose disposal and a markedly enhanced insulin response in mice treated with vildagliptin. After eight weeks, a gastric tolerance test showed that vildagliptin improved glucose tolerance and markedly (approximately ten-fold) augmented the insulin response in association with augmented (approximately five-fold) levels of intact glucagon-like peptide-1 (GLP-1). Furthermore, after nine weeks, islets were isolated. Islets from vildagliptin-treated mice showed augmented glucose-stimulated insulin response and a normalization of the islet insulin content, which was reduced by approximately 50% in transgenic controls versus wildtype animals. Double immunostaining of pancreatic islets for insulin and glucagon revealed that transgenic islets displayed severely disturbed intra-islet topography with frequently observed centrally located alpha-cells. Treatment with vildagliptin restored the islet topography. We therefore conclude that DPP-4 inhibition improves islet function and islet topography in mice with beta-cell specific transgenic overexpression of human IAPP.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adamantane,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid,
http://linkedlifedata.com/resource/pubmed/chemical/DPP4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptidyl Peptidase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptidyl-Peptidase IV Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon-Like Peptide 1,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Islet Amyloid Polypeptide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/vildagliptin
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0167-0115
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
4
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pubmed:volume |
143
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
97-103
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:17482289-Adamantane,
pubmed-meshheading:17482289-Amyloid,
pubmed-meshheading:17482289-Animals,
pubmed-meshheading:17482289-Dipeptidyl Peptidase 4,
pubmed-meshheading:17482289-Dipeptidyl-Peptidase IV Inhibitors,
pubmed-meshheading:17482289-Female,
pubmed-meshheading:17482289-Glucagon-Like Peptide 1,
pubmed-meshheading:17482289-Glucose,
pubmed-meshheading:17482289-Glucose Tolerance Test,
pubmed-meshheading:17482289-Humans,
pubmed-meshheading:17482289-Immunohistochemistry,
pubmed-meshheading:17482289-Insulin,
pubmed-meshheading:17482289-Insulin-Secreting Cells,
pubmed-meshheading:17482289-Islet Amyloid Polypeptide,
pubmed-meshheading:17482289-Islets of Langerhans,
pubmed-meshheading:17482289-Mice,
pubmed-meshheading:17482289-Mice, Transgenic,
pubmed-meshheading:17482289-Nitriles,
pubmed-meshheading:17482289-Pyrrolidines
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pubmed:year |
2007
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pubmed:articleTitle |
DPP-4 inhibition improves glucose tolerance and increases insulin and GLP-1 responses to gastric glucose in association with normalized islet topography in mice with beta-cell-specific overexpression of human islet amyloid polypeptide.
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pubmed:affiliation |
Department of Clinical Sciences, Lund University, Lund, Sweden. Bo.Ahren@med.lu.se
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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