Novel ABCA1 peptide agonists with antidiabetic action

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Salman Azhar
  • Stefanie Bittner
  • Jie Hu
  • Wen Jun Shen
  • Yuan Cortez
  • Xiao Hao
  • Lu Han
  • Jens O. Lagerstedt
  • Fredric B. Kraemer
  • Jan O. Johansson
Organisations
External organisations
  • Stanford University
  • First Affiliated Hospital of Zhengzhou University
  • VA Palo Alto Health Care System
  • Artery Therapeutics Inc.
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes

Keywords

  • Atherosclerosis, Diet induced diabetes, Glucose homeostasis, HDL mimetic, Insulin secretagogue, Type 2 diabetes
Original languageEnglish
Pages (from-to)1-11
JournalMolecular and Cellular Endocrinology
Volume480
Publication statusPublished - 2019 Jan 15
Publication categoryResearch
Peer-reviewedYes