liraglutide brands

Molecular formula: C172H265N43O51

Liraglutide is an acylated synthetic glucagon-like peptide-1 analog. Liraglutide is an agonist of the glucagon-like peptide-1 receptor which is coupled to adenylate cyclase. The increase in cyclic AMP stimulates the glucose dependant release of insulin, inhibits the glucose dependant release of glucagon, and slows gastric emptying to increase control of blood sugar. Liraglutide is an acylated, long-acting, human glucagon-like peptide-1 (GLP-1) receptor agonist; the synthetic (recombinant DNA origin) peptide precursor of liraglutide has 97% amino acid sequence homology to endogenous human GLP-1-(7-37). Liraglutide is prepared by attaching palmitic acid with a glutamic acid spacer on the lysine residue at position 26 of the peptide precursor. GLP-1-(7-37) represents less than 20% of total circulating endogenous GLP-1. Like GLP-1-(7-37), liraglutide activates the GLP-1 receptor in pancreatic beta cells. Liraglutide also increases intracellular cyclic 3',5'-adenosine monophosphate (cAMP) leading to insulin release in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. In addition, liraglutide suppresses glucagon secretion in a glucose-dependent manner but does not impair normal glucagon response to hypoglycemia. Liraglutide delays gastric emptying, reducing the rate at which postprandial glucose appears in the circulation. As a result of these actions resulting in increased insulin secretion, suppression of glucagon secretion, and delays in gastric emptying, liraglutide effectively reduces fasting and postprandial plasma glucose concentrations in patients with type 2 diabetes mellitus. Liraglutide is a glucagon-like peptide-1 (GLP-1) mimetic used for the treatment of Type 2 diabetes. Similar to the actions of endogenous GLP-1, liraglutide potentiates the post-prandial release of insulin, inhibits glucagon release and increases satiety. Recent epidemiological studies and clinical trials have suggested that treatment with GLP-1 mimetics may also diminish the risk of cardiovascular disease in diabetic patients. The mechanism responsible for this effect has yet to be determined; however, one possibility is that they might do so by a direct effect on vascular endothelium. Since low grade inflammation of the endothelium is an early event in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD), we determined the effects of liraglutide on inflammation in cultured human aortic endothelial cells (HAECs). Liraglutide reduced the inflammatory responses to TNFalpha and LPS stimulation, as evidenced by both reduced protein expression of the adhesion molecules VCAM-1 and E-Selectin, and THP-1 monocyte adhesion. This was found to result from increased cell Ca2+ and several molecules sensitive to Ca2+ with known anti inflammatory actions in endothelial cells, including CaMKKbeta, CaMKI, AMPK, eNOS and CREB. Treatment of the cells with STO-609, a CaMKK inhibitor, diminished both the activation of AMPK, CaMKI and the inhibition of TNFa and LPS-induced monocyte adhesion by liraglutide. Likewise, expression of an shRNA against AMPK nullified the anti-inflammatory effects of liraglutide. The results indicate that liraglutide exerts a strong anti-inflammatory effect on HAECs. They also demonstrate that this is due to its ability to increase intracellular Ca2+ and activate CAMKKbeta, which in turn activates AMPK. In vivo, liraglutide lowers blood glucose and body weight in a number of diabetic and obese models using rodents, pigs and monkeys. The mechanism of action in vivo involved glucose-dependent increase in insulin secretion, lowered glucagon secretion, decreased gastric emptying, loss of body fat, lowered food intake, altered food preference, and maintained energy expenditure. The mechanism of action is consistent with a specific GLP-1 effect. Liraglutide is a long-acting GLP-1 analogue, designed to bind to albumin as the main molecular mec

Source: PubChem (NCBI) · compound 16134956