Source:http://linkedlifedata.com/resource/pubmed/id/15749809
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2005-3-7
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pubmed:abstractText |
Glucagon-like peptide 1 (GLP-1) analogues are considered potential drugs for type 2 diabetes. We studied the effect of a novel GLP-1 analogue, S 23521 ([a8-des R36] GLP-1-[7-37]-NH2), on the metabolic state and beta-cell function, proliferation and survival in the Psammomys obesus model of diet-induced type 2 diabetes. Animals with marked hyperglycaemia after 6 days of high-energy diet were given twice-daily s.c. injection of 100 microg/kg S 23521 for 15 days. Food intake was significantly decreased in S 23251-treated P. obesus; however, there was no significant difference in body weight from controls. Progressive worsening of hyperglycaemia was noted in controls, as opposed to maintenance of pre-treatment glucose levels in the S 23521 group. Prevention of diabetes progression was associated with reduced mortality. In addition, the treated group had higher serum insulin, insulinogenic index and leptin, whereas plasma triglyceride and non-esterified fatty acid levels were decreased. S 23521 had pronounced effect on pancreatic insulin, which was 5-fold higher than the markedly depleted insulin reserve of control animals. Immunohistochemical analysis showed islet degranulation with disrupted morphology in untreated animals, whereas islets from S 23521-treated animals appeared intact and filled with insulin; beta-cell apoptosis was approximately 70% reduced, without a change in beta-cell proliferation. S 23521 treatment resulted in a 2-fold increase in relative beta-cell volume. Overall, S 23521 prevented the progression of diabetes in P. obesus with marked improvement of the metabolic profile, including increased pancreatic insulin reserve, beta-cell viability and mass. These effects are probably due to actions of S 23521 both directly on islets and via reduced food intake, and emphasize the feasibility of preventing blood glucose deterioration over time in type 2 diabetes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glucagon,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoglycemic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Leptin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-0795
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
184
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
505-13
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15749809-Animals,
pubmed-meshheading:15749809-Cell Proliferation,
pubmed-meshheading:15749809-Cell Survival,
pubmed-meshheading:15749809-Diabetes Mellitus, Type 2,
pubmed-meshheading:15749809-Diet,
pubmed-meshheading:15749809-Female,
pubmed-meshheading:15749809-Gerbillinae,
pubmed-meshheading:15749809-Glucagon,
pubmed-meshheading:15749809-Hypoglycemic Agents,
pubmed-meshheading:15749809-Insulin,
pubmed-meshheading:15749809-Islets of Langerhans,
pubmed-meshheading:15749809-Leptin,
pubmed-meshheading:15749809-Male,
pubmed-meshheading:15749809-Models, Animal,
pubmed-meshheading:15749809-Peptide Fragments,
pubmed-meshheading:15749809-Protein Precursors
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pubmed:year |
2005
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pubmed:articleTitle |
Improvement of metabolic state in an animal model of nutrition-dependent type 2 diabetes following treatment with S 23521, a new glucagon-like peptide 1 (GLP-1) analogue.
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pubmed:affiliation |
Endocrinology and Metabolism Service, Department of Internal Medicine and The Hadassah Diabetes Center, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120, Israel.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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