Novel ABCA1 peptide agonists with antidiabetic action

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

Research output: Contribution to journalArticlepeer-review

2 Citations (SciVal)

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.

Original languageEnglish
Pages (from-to)1-11
JournalMolecular and Cellular Endocrinology
Volume480
DOIs
Publication statusPublished - 2019 Jan 15

Subject classification (UKÄ)

  • Endocrinology and Diabetes

Keywords

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

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