کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8477266 | 1550896 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Characterisation of structurally modified analogues of glucagon as potential glucagon receptor antagonists
ترجمه فارسی عنوان
مشخص نمودن آنالوگ های اصلاح شده ساختاری گلوکاگون به عنوان آنتاگونیست های گیرنده گلوکاگون
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
چکیده انگلیسی
Acute in vitro and in vivo biological activities of four novel structural analogues of glucagon were tested. desHis1Pro4-glucagon, desHis1Pro4Glu9-glucagon, desHis1Pro4Glu9Lys12FA-glucagon and desHis1Pro4Glu9Lys30FA-glucagon were stable to DPP-4 degradation and dose-dependently inhibited glucagon-mediated cAMP production (p < 0.05 to p < 0.001). None stimulated insulin secretion in vitro above basal levels, but all inhibited glucagon-induced insulin secretion (p < 0.01 to p < 0.001). In normal mice all analogues antagonised acute glucagon-mediated elevations of blood glucose (p < 0.05 to p < 0.001) and blocked corresponding insulinotropic responses. In high-fat fed mice, glucagon-induced increases in plasma insulin (p < 0.05 to p < 0.001) and glucagon-induced hyperglycaemia were blocked (p < 0.05 to p < 0.01) by three analogues. In obese diabetic (ob/ob) mice only desHis1Pro4Glu9-glucagon effectively (p < 0.05 to p < 0.01) inhibited both glucagon-mediated glycaemic and insulinotropic responses. desHis1Pro4-glucagon and desHis1Pro4Glu9-glucagon were biologically ineffective when administered 8 h prior to glucagon, whereas desHis1Pro4Glu9Lys12FA-glucagon retained efficacy (p < 0.01) for up to 24 h. Such peptide-derived glucagon receptor antagonists have potential for type 2 diabetes therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 381, Issues 1â2, 5 December 2013, Pages 26-34
Journal: Molecular and Cellular Endocrinology - Volume 381, Issues 1â2, 5 December 2013, Pages 26-34
نویسندگان
F.P.M. O'Harte, Z.J. Franklin, E.P. Rafferty, N. Irwin,