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Novel ABCA1 peptide agonists with antidiabetic action

Azhar, Salman; Bittner, Stefanie; Hu, Jie; Shen, Wen Jun; Cortez, Yuan; Hao, Xiao; Han, Lu; Lagerstedt, Jens O. LU ; Kraemer, Fredric B. and Johansson, Jan O. (2019) In Molecular and Cellular Endocrinology 480. p.1-11
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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Diet induced diabetes, Glucose homeostasis, HDL mimetic, Insulin secretagogue, Type 2 diabetes
in
Molecular and Cellular Endocrinology
volume
480
pages
1 - 11
publisher
Elsevier
external identifiers
  • scopus:85057571983
ISSN
0303-7207
DOI
10.1016/j.mce.2018.09.011
language
English
LU publication?
yes
id
7f5f670b-0e25-4290-a470-9850ba25dc9a
date added to LUP
2018-12-21 09:25:29
date last changed
2019-02-20 11:40:36
@article{7f5f670b-0e25-4290-a470-9850ba25dc9a,
  abstract     = {<p>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.</p>},
  author       = {Azhar, Salman and Bittner, Stefanie and Hu, Jie and Shen, Wen Jun and Cortez, Yuan and Hao, Xiao and Han, Lu and Lagerstedt, Jens O. and Kraemer, Fredric B. and Johansson, Jan O.},
  issn         = {0303-7207},
  keyword      = {Atherosclerosis,Diet induced diabetes,Glucose homeostasis,HDL mimetic,Insulin secretagogue,Type 2 diabetes},
  language     = {eng},
  month        = {01},
  pages        = {1--11},
  publisher    = {Elsevier},
  series       = {Molecular and Cellular Endocrinology},
  title        = {Novel ABCA1 peptide agonists with antidiabetic action},
  url          = {http://dx.doi.org/10.1016/j.mce.2018.09.011},
  volume       = {480},
  year         = {2019},
}