کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8348279 1541719 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ablation of glucagon receptor signaling by peptide-based glucagon antagonists improves glucose tolerance in high fat fed mice
ترجمه فارسی عنوان
تخریب سیگنال گیرنده گلوکاگون توسط آنتاگونیست های گلوکاگون مبتنی بر پپتید باعث افزایش تحمل گلوکز در موش های پرچرب
کلمات کلیدی
آنتاگونیست گلوکاگون، دیابت، تحمل گلوکز، حساسیت به انسولین،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
چکیده انگلیسی
Modification to the structure of glucagon has provided a number of glucagon receptor antagonists with possible therapeutic application for diabetes. These novel peptide analogs include desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon. This study has evaluated the metabolic benefits of once daily administration of desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon in high fat (45%) fed mice for 15 days. Administration of desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon had no significant effect on body weight, food intake or circulating glucose concentrations during the treatment period. However, both peptides significantly (P < 0.05 to P < 0.01) reduced circulating plasma insulin concentrations from day 6 onwards. Oral glucose tolerance and insulin sensitivity, as assessed by exogenous insulin administration, were significantly (P < 0.01 to P < 0.001) improved by both desHis1Pro4Glu9-glucagon and desHis1Pro4Glu9(Lys30PAL)-glucagon. These metabolic benefits were accompanied by significantly (P < 0.01) increased pancreatic insulin stores. No significant differences in blood triacylglycerol or cholesterol levels were noted with desHis1Pro4Glu9-glucagon, however desHis1Pro4Glu9(Lys30PAL)-glucagon treatment significantly (P < 0.01) increased HDL-cholesterol levels. Glucagon-mediated elevations of glucose and insulin were effectively (P < 0.01 to P < 0.001) annulled in both treatment groups on day 15. Interestingly, glucose levels during an intraperitoneal glucose tolerance test were not altered by either desHis1Pro4Glu9-glucagon or desHis1Pro4Glu9(Lys30PAL)-glucagon treatment. These data provide further evidence that glucagon antagonism could provide an effective means of treating T2DM.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 60, October 2014, Pages 95-101
نویسندگان
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