期刊
PEPTIDES
卷 60, 期 -, 页码 95-101出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2014.08.002
关键词
Glucagon antagonist; Diabetes; Glucose tolerance; Insulin sensitivity
资金
- Department of Education and Learning, Northern Ireland
- University of Ulster
- Invest Northern Ireland [POC106]
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 desHis(1)Pro(4)Glu(9)-glucagon and desHis(1)Pro(4)Glu(9)(Lys(30)PAL)-glucagon. This study has evaluated the metabolic benefits of once daily administration of desHis(1)Pro(4)Glu(9)-glucagon and desHis(1)Pro(4)Glu(9)(Lys(30)PAL)-glucagon in high fat (45%) fed mice for 15 days. Administration of desHis(1)Pro(4)Glu(9)-glucagon and desHis(1)Pro(4)Glu(9)(Lys(30)PAL)-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 desHis(1)Pro(4)Glu(9)-glucagon and desHis(1)Pro(4)Glu(9)(Lys(30)PAL)-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 notedwith desHis(1)Pro(4)Glu(9)-glucagon, however desHis(1)Pro(4)Glu(9)(Lys(30)PAL)-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 desHis(1)Pro(4)Glu(9)-glucagon or desHis(1)Pro(4)Glu(9)(Lys(30)PAL)-glucagon treatment. These data provide further evidence that glucagon antagonism could provide an effective means of treating T2DM. (C) 2014 Elsevier Inc. All rights reserved.
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