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Int J Mol Sci (2013) 14(11):2151324

While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention

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In the obesity group, there was a significant and clinically meaningful reduction in body weight of 4.74% at week 8, with weight continuously decreasing during the 8-week treatment period.175 Classical pathophysiological mechanisms of GLP-1 GLP-1 signaling pathway GLP-1 initiates signaling by binding to its receptor, GLP-1R, which is a G-protein-coupled receptor.176,177 When GLP-1 binds to GLP-1R, it triggers the activation of G-proteins, leading to an increase in the intracellular second messenger cAMP.34,39,177 The rise in cAMP activates protein kinase A (PKA), which then promotes the synthesis and secretion of insulin and inhibits the release of glucagon.178,179 Additionally, cAMP can activate Rap1 through EPAC (Exchange Protein directly Activated by cAMP),180,181,182 which is involved in regulating insulin secretion.180,181,183 GLP-1 also activates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, which is crucial for maintaining the survival and function of pancreatic -cells.184,185,186,187 GLP-1 (GLP-1RAs) GLP-1RAs , .37 GLP-1RAs , .171 GLP-1RAs GLP-1RAs ,

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