GLP-1 - , .198,205,206 GLP-1 .207,208,209 GLP-1 .176,210,211 PYY, CCK, , .212,213 The pathophysiological mechanism of GLP-1 in metabolic diseases GLP-1 plays a crucial role in the pathophysiology of metabolic diseases, particularly in T2DM and obesity.213,214,215 Role of GLP-1 in T2DM GLP-1 significantly influences the functionality of pancreatic -cells and -cells, contributing to its therapeutic effect on T2DM.132,216,217 As a vital incretin hormone, GLP-1 enhances glucose-dependent insulin secretion.3 It also promotes proliferation and reduces apoptosis of pancreatic -cells, thereby maintaining their quality and functionality.130,218 At the molecular level, GLP-1 activates the cAMP response element-binding protein (CREB) via its receptor (GLP-1R), a transcription factor crucial for expressing the insulin gene.3,130,219 GLP-1 also activates PKA and EPAC through a cAMP-dependent pathway.1,220 PKA, a key enzyme, phosphorylates various target proteins, affecting their activity and function, which in turn promotes insulin synthesis and secretion.178,180 The PI3K/Akt signaling pathway, activated by GLP-1, plays a vital role in maintaining pancreatic -cell survival and promoting their proliferation.221,222 Activation of Akt stimulates -cell proliferation, reduces apoptosis, and enhances insulin secretion by regulating downstream effector molecules like Forkhead box protein O1 (FoxO1) and the glucose transporter type 2 (GLUT2).223,224 GLP-1 also inhibits glucagon release from -cells, which is beneficial for reducing blood glucose levels since glucagon promotes hepatic gluconeogenesis.131,225 GLP-1s action on -cells regulates glucagon release.131 The direct impact of GLP-1 on these cells slows the secretion of glucagon, essential for maintaining glucose stability, especially postprandially.131,226 When GLP-1 binds to its receptor on -cells, it activates intracellular cAMP production.227 In -cells, increased cAMP affects glucagon synthesis and release.228 PKA, activated by cAMP, can regulate the activity of K-ATP channels in -cells.228,229 The opening of these channels is controlled by the intracellular ATP/ADP ratio.229 Specifically, PKA modifies the open state of K-ATP channels through phosphorylation, affecting the cell membranes potential and intracellular calcium ion concentration.230,231 By modulating the activity of K-ATP channels, GLP-1 indirectly controls the calcium signaling in -cells, thereby influencing glucagon secretion.232,233 GLP-1 inhibits the release of glucagon from -cells through multiple mechanisms
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GLP-1s are a natural hormone made of peptides in your body, and recently, peptides have surged in popularity in the fitness and wellness space
Weeks 9-12: Progress to 4mg weekly
