Cardiomyocytes isolated selleck chem Axitinib from both GLP 1 receptor knockout mice and re spective wild type animals responded to lixisenatide with an increase in fractional shortening. Expression of genes involved in the GLP 1 incretin axis A local GLP 1 release may exist in the heart, potentially Inhibitors,Modulators,Libraries competing with lixisenatide on the GLP 1 receptor. There fore we analyzed tissues for the expression of the GLP 1 precursor peptide, glucagon, and converting and degrading proteases, PCSK1, PCSK2 and DPP4. Neither GCG, nor PCSK1 or PCSK2 expression could be observed in cardiac Inhibitors,Modulators,Libraries samples ruling out the existence of a local GLP 1 generation. In parallel we determined the expression of GLP 1 recep tor using two different specific Taqman primer assays span ning different exonintron within the known rat sequence.

Use of both primers assays indicated a similar strong expression in pancreas, isolated pancreatic islets and lung, but failed to amplify specifically any signal from car diac tissue and cardiomyocytes. It seems that all cardiac tis sues lack Inhibitors,Modulators,Libraries components of a local incretin system with Inhibitors,Modulators,Libraries DPP IV being the exception. Discussion Since the early 1990s GLP 1 peptides and analogs have been investigated for treating T2DM because of their ability to enhance glucose dependent insulin secretion. In addition, GLP 1 agonists are hypothesized to have effects on the cardiovascular system beyond glycaemic control, which may be exploited for therapeutic benefit. Cardiovascular disease is the leading cause of death in pa tients with type 2 diabetes. In a recent prospective cohort study of one million U. S.

adults, diabetes was associated with a twofold increase in the risk of death from ischemic heart disease. Concerns about the cardiovascular safety of anti diabetic drugs resulted in the FDA recommendation that the CV risk should be more thoroughly addressed dur ing drug development. As a consequence of this new guideline cardiovascular Inhibitors,Modulators,Libraries outcome studies are currently on going in more than 26,000 type 2 diabetic patients directly treated with GLP 1 receptor agonists and more than 40,000 treated with a DPP IV inhibitors which also may act indir ectly via GLP 1. The overall goal of our study was to dem onstrate in a pre clinical set of models cardioprotective effects of the GLP 1 analog lixisenatide, building a further fundament for clinical testing in patients with reduced car diac function. In an acute model of global cardiac ischemia reperfusion injury, lixisenatide treatment during the last 10 minutes of ischemia and during the whole reperfusion period signifi cantly reduced infarct size. The observed cardioprotective effect was not associated http://www.selleckchem.com/products/Bicalutamide(Casodex).html with a significant change in car diac hemodynamics, as assessed by rate pressure product RPP, and particularly coronary flow.