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doi: 10.1161/CIR.0000000000000485 576 LiuXDuXHanGGaoW

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Even with lower prices, there is little evidence to date to suggest that the expanded use of GLP-1s will be offset by lower spending on other health care services in the short term, even though the drugs do provide significant health benefits to users

Several in vitro and in vivo results have expanded the role of these molecules from potentiating glucose-stimulated insulin secretion to promoting -cell survival under different stressful environments by favoring proliferation, neogenesis and resistance to apoptosis ( via secretion of IGF-2 from the same cells ( In agreement with experimental studies, GLP-1 analogues, particularly liraglutide, sustain the maintenance of -cell function in obese individuals with early T2D, and these effects are presumably independent of weight loss ( Further, experimental data suggest that the pro-survival action of GLP-1RAs may also be mediated by the Akt-dependent stimulation of the mTORC1/S6K1 pathway, the activation of which is dependent upon the IGF-1R, as observed in rodent islet cells ( in vitro , exendin-4 lost the ability to activate this pathway, suggesting that GLP-1 analogues may restore -cell proliferation via autocrine or paracrine activation of IGF-1R ( In concert, these results define a new scenario of action for incretin-based therapy that may involve the adipo-insular axis, linking the weight lowering competence with the sustained protection of -cells from diabetogenic stressors

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