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Jens Lagerstedt

Associate professor

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Novel ABCA1 peptide agonists with antidiabetic action

Author

  • Salman Azhar
  • Stefanie Bittner
  • Jie Hu
  • Wen Jun Shen
  • Yuan Cortez
  • Xiao Hao
  • Lu Han
  • Jens O. Lagerstedt
  • Fredric B. Kraemer
  • Jan O. Johansson

Summary, in English

Previously, apoE-derived ABCA1 agonist peptides have been shown to possess anti-atherosclerotic and possibly antidiabetic properties. Here we assessed the in vitro and in vivo actions of a second generation of ABCA1 peptide agonists, CS6253 and T6991-2, on glucose homeostasis. The results show that these two peptides improve glucose tolerance in a prediabetic diet-induced obesity mouse model by enhancing insulin secretion. It was further demonstrated that T6991-2 also improved glucose tolerance in leptin-deficient (ob/ob) mice. CS6253 increased insulin secretion both under basal conditions and in response to high glucose stimulation in pancreatic INS-1 β-cells rendered leptin receptor deficient with specific siRNA. Additional in vitro cell studies suggest that the CS6253 agonist attenuates hepatic gluconeogenesis and glucose transport. It also potentiates insulin-stimulated glucose uptake and utilization. These observed anti-diabetic actions suggest additional benefits of the CS6253 and T6991-2 ABCA1 peptide agonists for cardiovascular disease beyond their direct anti-atherosclerosis properties previously described.

Department/s

  • Medical Protein Science
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2019-01-15

Language

English

Pages

1-11

Publication/Series

Molecular and Cellular Endocrinology

Volume

480

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • Atherosclerosis
  • Diet induced diabetes
  • Glucose homeostasis
  • HDL mimetic
  • Insulin secretagogue
  • Type 2 diabetes

Status

Published

Research group

  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 0303-7207