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Highlighting the strong link between inflammation-related epithelial metabolism and Gcg expression, mRNA levels of Hk2 and Ddit4 , genes involved in glycolysis and suppressing mammalian target of rapamycin (mTOR) activity (67, 68), negatively correlated with Gcg expression, while a positive correlation was observed for Pck1 and Hmgcs2 , genes involved in gluconeogenesis and ketogenesis, respectively ( Figure 4E )

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Remarkably, the mechanisms underlying the positive effects of GLP-1 RAs appear complementary to that of SGLT-2 inhibitors (SGLT2i), a therapeutic pillar of the treatment for both HFrEF and HFpEF, providing incremental benefits in reducing HF exacerbations and hospitalizations [45]