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FIGURE 1 Notably, the insulinotropic actions of circulating GLP-1 are facilitated through a two-domain binding interaction with GLP-1R (Figure 2), a structurally well-characterized prototypical class B GPCR, which recruits the G s -subunit of the heterotrimeric G-protein for cAMP-mediated downstream signaling, involving protein kinase A (PKA) and exchange protein activated by cAMP (EPAC), leading to insulin exocytosis
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345,346 GLP-1 may also reduce the expression of cartilage-degrading enzymes by inhibiting the MAPK pathway or activating anti-inflammatory pathways such as PI3K/Akt, thereby alleviating cartilage damage
