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Jens Lagerstedt

Associate professor

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ApoAI-derived peptide increases glucose tolerance and prevents formation of atherosclerosis in mice

Author

  • Shelley J Edmunds
  • Rebeca Liébana-García
  • Oktawia Nilsson
  • Joan Domingo-Espín
  • Caitriona Grönberg
  • Karin G Stenkula
  • Jens O Lagerstedt

Summary, in English

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 Leprdb 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 Leprdb 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.

Department/s

  • Medical Protein Science
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Faculty of Medicine
  • Glucose Transport and Protein Trafficking

Publishing year

2019-05-08

Language

English

Pages

1257-1267

Publication/Series

Diabetologia

Volume

62

Issue

7

Document type

Journal article

Publisher

Springer

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Medical Protein Science
  • Glucose Transport and Protein Trafficking

ISBN/ISSN/Other

  • ISSN: 1432-0428