期刊
DIABETOLOGIA
卷 62, 期 7, 页码 1257-1267出版社
SPRINGER
DOI: 10.1007/s00125-019-4877-2
关键词
ApoA-I; Atherosclerosis; Cardiovascular disease; Diabetes; Glucose tolerance test; Glycaemic control; HDL; Insulin; Peptide; RG54
资金
- Swedish Research council [K2014-54X-22426-01-3, 2009-1039]
- Swedish Diabetes Foundation
- Albert Pahlsson Foundation
- NovoNordisk Foundation (NovoSeeds)
- Vinnova (Sweden's Innovation Agency) [2015-01549]
- Royal Physiographic Society in Lund
- Sten K. Johnson Foundation
- NovoNordisk STAR Postdoc programme
- Swedish Foundation for Strategic Research [IRC15-0067]
- Vinnova [2015-01549] Funding Source: Vinnova
Aims/hypothesis Finding new treatment alternatives for individuals with diabetes with severe insulin resistance is highly desired. To identify novel mechanisms that improve glucose uptake in skeletal muscle, independently from insulin levels and signalling, we have explored the therapeutic potential of a short peptide sequence, RG54, derived from apolipoprotein A-I (ApoA-I). Methods INS-1E rat clonal beta cells, C2C12 rat muscle myotubes and J774 mouse macrophages were used to study the impact of RG54 peptide on glucose-stimulated insulin secretion, glucose uptake and cholesterol efflux, respectively. GTTs were carried out on diet-induced insulin-resistant and Lepr(db) diabetic mouse models treated with RG54 peptide, and the impact of RG54 peptide on atherosclerosis was evaluated in Apoe(-/-) mice. Control mice received ApoA-I protein, liraglutide or NaCl. Results The synthetic RG54 peptide induced glucose uptake in cultured muscle myotubes by a similar amount as insulin, and also primed pancreatic beta cells for improved glucose-stimulated insulin secretion. The findings were verified in diet-induced insulin-resistant and Lepr(db) diabetic mice, jointly confirming the physiological effect. The RG54 peptide also efficiently catalysed cholesterol efflux from macrophages and prevented the formation of atherosclerotic plaques in Apoe(-/-) mice. Conclusions/interpretation The RG54 peptide exhibits good prospects for providing glucose control and reducing the risk of cardiovascular disease in individuals with severe insulin resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据