Novel ABCA1 peptide agonists with antidiabetic action.
ATP Binding Cassette Transporter 1
/ pharmacology
Animals
Atherosclerosis
/ pathology
Cell Line
Cell Line, Tumor
Diet, High-Fat
Disease Models, Animal
Exenatide
/ pharmacology
Gluconeogenesis
/ drug effects
Glucose
/ metabolism
Glucose Tolerance Test
Glycated Hemoglobin
/ metabolism
Humans
Hypoglycemic Agents
/ pharmacology
Insulin Resistance
Insulin Secretion
/ drug effects
Leptin
/ metabolism
Liver
/ metabolism
Mice, Inbred C57BL
Mice, Knockout
Mice, Obese
Obesity
/ pathology
Peptides
/ pharmacology
Rats
Triglycerides
/ metabolism
Atherosclerosis
Diet induced diabetes
Glucose homeostasis
HDL mimetic
Insulin secretagogue
Type 2 diabetes
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
15 01 2019
15 01 2019
Historique:
received:
03
07
2018
revised:
19
09
2018
accepted:
30
09
2018
pubmed:
6
10
2018
medline:
18
5
2019
entrez:
6
10
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30290217
pii: S0303-7207(18)30281-8
doi: 10.1016/j.mce.2018.09.011
pmc: PMC6626528
mid: NIHMS1010534
pii:
doi:
Substances chimiques
ATP Binding Cassette Transporter 1
0
Glycated Hemoglobin A
0
Hypoglycemic Agents
0
Leptin
0
Peptides
0
Triglycerides
0
Exenatide
9P1872D4OL
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-11Subventions
Organisme : BLRD VA
ID : I01 BX000398
Pays : United States
Organisme : BLRD VA
ID : I01 BX001923
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK116074
Pays : United States
Informations de copyright
Copyright © 2018. Published by Elsevier B.V.
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