Novel ABCA1 peptide agonists with antidiabetic action

Publication date: Available online 2 October 2018Source: Molecular and Cellular EndocrinologyAuthor(s): Salman Azhar, Stefanie Bittner, Jie Hu, Wen-Jun Shen, Yuan Cortez, Xiao Hao, Han Lu, Jens O. Lagerstedt, Fredric B. Kraemer, Jan O. JohanssonAbstractPreviously, 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 about cardiovascular disease beyond their direct anti-atherosclerosis properties previously described.

Source: Molecular and Cellular Endocrinology - October 5, 2018 Category: Endocrinology Source Type: research