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The limitation shows up at higher doses

doi: 10.1007/s10545-010-9242-z 5

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For example, incubation with GLP-1 (736) or an analog inhibits the activation of apoptotic and necrotic processes and increases the viability of neonatal cardiomyocytes under ischemia-reperfusion conditions40,41 and in the presence of stimuli characteristic of HF, such as tumor necrosis factor (TNF)-alpha.42 Moreover, incubation of adult mouse cardiomyocytes (HL-1 line) in the presence of GLP-1 (736) prevents the activation of mechanisms involved in death cell processes triggered by classical apoptotic stimuli such as staurosporine and by stimuli inherent to the diabetic setting such as palmitate and ceramide.43 In addition, in all these experiments, the cytoprotective effects of GLP-1 (736) were shown to be primarily mediated by mechanisms dependent on the activation of the RISK pathway, mainly phosphoinositol 3-kinase (PI3K) and extracellular signal-regulated kinases (ERK1/2) (Fig