An ANOVA analysis provided a few num ber of genes differentially regulated by lixisenatide versus placebo kinase inhibitor ARQ197 in the infarct area. Interestingly, lixisenatide was equipotent to GLP 1 and other GLP 1 receptor analogues on reducing infarct size in perfused isolated rat hearts. In contrast, lixisenatide at higher concentrations, but not GLP 1, improved frac tional shortening in isolated cardiomyocytes. This might suggest that lixisenatide displays acute cardioprotection via the GLP 1 receptor, while effects of lixisenatide on contractility are mediated by a different signalling path way. In line with our findings, Vila Petroff et al. showed the lack of contractility promoting effect of GLP 1 in isolated cardiomyocytes.

We supplemented their findings by demonstrating that even very high concentra tions of the GLP 1 peptide, not amenable to rapid degrad ation by dipeptidyl peptidase IV, were ineffective. Finally, when performing Inhibitors,Modulators,Libraries a similar set of experiments on cardiomyocytes from GLP 1 receptor knockout mice, a robust response to lixisenatide remained suggesting a GLP 1 receptor independent effect lixisenatide on the contractility response. Lixisenatide displayed beneficial effects in our rodent models, but GLP 1 receptor mRNA was not detectable without ambiguity. Two different PCR Taqman probes, located to different parts of the rat gene, did not reveal abundant expression of the GLP 1 receptor in rat hearts and cardiomyocytes, but indicated a strong expression in other organs like rat pancreas. Overall, controversial data on the expression of the GLP 1 receptor in mam malian cardiac tissues exists.

GLP 1 receptor mRNA expression in human heart samples was detected by an RNA protection assay. In contrast, using autora diography with a radio labeled GLP 1, no staining was detected in human heart despite several other organs be ing positive for this ligand. Inhibitors,Modulators,Libraries An antibody against the GLP 1 receptor stained in mouse heart several cell Inhibitors,Modulators,Libraries types. Later it was shown that available antibodies against the GLP 1 receptor display strong cross reactivity in cells not expressing the GLP 1 receptor. Hence, immunostainings should be carefully considered as long as specificity is not clearly demonstrated. Simultaneously to immunostainings, Ban et al. detected mRNA for the GLP1 receptor, using an endpoint PCR with a high number of amplification cycles followed by specific hybridization.

This methodology does not rule out a very low expression level in the samples. Bullock and co workers used the RNAse protection assay, a more quan titative but less Inhibitors,Modulators,Libraries sensitive methodology, to assess mRNA distribution in rat tissues for the GLP 1 receptor. They could not confirm Inhibitors,Modulators,Libraries expression in the rat heart www.selleckchem.com/products/Rapamycin.html in contrast to other positive tissues like pancreatic tissues. Currently, we cannot exclude that a GLP1R variant is expressed in the heart which is not detectable using the two different PCR primer assays.