Figure 3. Summary of insulinotropic and insulinomimetic effects of GLP-1 and its cleavage products in pancreatic β-cells. The cleavage of GLP-1(7–36)amide (defined as 7–36amide) by DPP-IV leads to the production of GLP-1(9–36)amide (defined as 9–36amide). The cleavage by NEP 24.11 leads to the production of GLP-1 (28–36)amide (defined as 28–36amide). GLP-1R mediates the insulinotropic effect of 7–36amide and GLP-1R agonists, such as exendin-4, involving both cAMP/PKA and cAMP/Epac. PKA can activate β-cat via increasing its Ser675 phosphorylation, which is at least partially responsible for the insulinomimetic effect of GLP-1. Whether 28–36amide exerts its insulinomimetic effect in pancreatic β-cells via a yet to be identified receptor, or a receptor independent mechanism remain to be further investigated. Whether or not 28–36amide exerts its insulinomimetic effect via stimulating β-cat Ser675 phosphorylation is also worth to be further examined.