| Novel, non-peptidic somatostatin receptor subtype 5 antagonists improve glucose tolerance in rodents. | |
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MedLine Citation:
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PMID: 19761802 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Somatostatin regulates numerous endocrine processes, including glucose homeostasis. The contribution and effects of the 5 somatostatin receptors are still unclear, in part due to the lack of suitable subtype specific receptor antagonists. We explored the effects of two novel, non-peptidic, orally bioavailable somatostatin receptor subtype 5 antagonists named Compound A and Compound B on glycemia in animal models of type 2 diabetes after an initial in vitro characterization. METHODS AND RESULTS: Compound A led to a dose-dependent decrease in glucose and insulin excursions during an OGTT in Zucker (fa/fa) rats after single treatment by up to 17% and 49%, respectively. Diet-induced obese mice showed after three weeks treatment with compounds A and B a dose-dependent decrease of the glucose excursion of up to 45% and 37%, respectively. In contrast to the acute effect observed in Zucker rats, Compound A showed a dose-dependent insulin increase by up to 72%, whereas body weight, liver triglycerides, ALT and AST were dose-dependently decreased. CONCLUSIONS: SSTR5 antagonists have the potential for short- and long-term improvements of the glucose homeostasis in rodent models of type 2 diabetes. Further work on the mechanism and the relevance for human disease is warranted. |
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Authors:
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Urs Sprecher; Peter Mohr; Rainer E Martin; Hans Peter Maerki; Rub?n Alvarez Sanchez; Alfred Binggeli; Basil K?nnecke; Andreas D Christ |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Regulatory peptides Volume: 159 ISSN: 1873-1686 ISO Abbreviation: Regul. Pept. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-12-17 Completed Date: 2010-02-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8100479 Medline TA: Regul Pept Country: Netherlands |
Other Details:
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Languages: eng Pagination: 19-27 Citation Subset: IM |
Affiliation:
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Discovery Research, Chemistry and Non-Clinical Safety, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Glucose / metabolism* Body Weight / drug effects CHO Cells Cricetinae Cricetulus Diabetes Mellitus, Experimental / blood, drug therapy* Dose-Response Relationship, Drug Homeostasis / drug effects Humans Hypoglycemic Agents / pharmacology* Liver / metabolism Mice Obesity / blood, drug therapy* Rats Rats, Zucker Receptors, Somatostatin / antagonists & inhibitors*, metabolism Triglycerides / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Blood Glucose; 0/Hypoglycemic Agents; 0/Receptors, Somatostatin; 0/Triglycerides; 0/somatostatin receptor 5 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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