GLP‐1 derivative liraglutide in rats with β‐cell deficiencies: influence of metabolic state on β‐cell mass dynamicsстатья из журнала
Аннотация: Liraglutide is a long‐acting GLP‐1 derivative, designed for once daily administration in type II diabetic patients. To investigate the effects of liraglutide on glycemic control and β ‐cell mass in rat models of β ‐cell deficiencies, studies were performed in male Zucker diabetic fatty (ZDF) rats and in 60% pancreatectomized rats. When liraglutide was dosed s.c. at 150 μ g kg −1 b.i.d. for 6 weeks in ZDF rats 6–8 weeks of age at study start, diabetes development was markedly attenuated. Blood glucose was approximately 12 m M lower compared to vehicle ( P <0.0002), and plasma insulin was 2–3‐fold higher during a normal 24‐h feeding period ( P <0.001). Judged by pair feeding, approximately 53% of the antihyperglycemic effect observed on 24‐h glucose profiles was mediated by a reduction in food intake, which persisted throughout the study and averaged 16% ( P <0.02). Histological analyses revealed that β ‐cell mass and proliferation were significantly lower in prediabetic animals still normoglycemic after 2 weeks treatment compared to vehicle‐treated animals that had begun to develop diabetes. When the treatment period was 6 weeks, the liraglutide‐treated animals were no longer completely normoglycemic and the β ‐cell mass was significantly increased compared to overtly diabetic vehicle‐treated animals, while β ‐cell proliferation was unaffected. In the experiments with 60% pancreatectomized rats, 8 days treatment with liraglutide resulted in a significantly lower glucose excursion in response to oral glucose compared to vehicle treatment. Again, part of the antihyperglycemic effect was due to reduced food intake. No effect of liraglutide on β ‐cell mass was observed in these virtually normoglycemic animals. In conclusion, treatment with liraglutide has marked antihyperglycemic effects in rodent models of β ‐cell deficiencies, and the in vivo effect of liraglutide on β ‐cell mass may in part depend on the metabolic state of the animals. British Journal of Pharmacology (2003) 140 , 123–132. doi: 10.1038/sj.bjp.0705397
Год издания: 2003
Авторы: Jeppe Sturis, C. F. Gotfredsen, John Rømer, Bidda Rolin, Ulla Ribel, Christian L. Brand, Michael Wilken, Karsten Wassermann, Carolyn F. Deacon, Richard D. Carr, Lotte Bjerre Knudsen
Издательство: Wiley
Источник: British Journal of Pharmacology
Ключевые слова: Pancreatic function and diabetes, Diabetes Treatment and Management, Metabolism, Diabetes, and Cancer
Другие ссылки: British Journal of Pharmacology (HTML)
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Том: 140
Выпуск: 1
Страницы: 123–132