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Interaction Between Leucine And Phosphodiesterase 5 Inhibition In Modulating Insulin Sensitivity And Lipid Metabolism, Lizhi Fu, Fenfen Li, Antje Bruckbauer, Qiang Cao, Xin Cui, Rui Wu, Hang Shi, Bingzhong Xue, Michael B. Zemel
Interaction Between Leucine And Phosphodiesterase 5 Inhibition In Modulating Insulin Sensitivity And Lipid Metabolism, Lizhi Fu, Fenfen Li, Antje Bruckbauer, Qiang Cao, Xin Cui, Rui Wu, Hang Shi, Bingzhong Xue, Michael B. Zemel
Biology Faculty Publications
Purpose: Leucine activates SIRT1/AMP-activated protein kinase (AMPK) signaling and markedly potentiates the effects of other sirtuin and AMPK activators on insulin signaling and lipid metabolism. Phosphodiesterase 5 inhibition increases nitric oxide–cGMP signaling, which in turn exhibits a positive feedback loop with both SIRT1 and AMPK, thus amplifying peroxisome proliferator-activated receptor γ co-activator α (PGC1α)-mediated effects. Methods: We evaluated potential synergy between leucine and PDE5i on insulin sensitivity and lipid metabolism in vitro and in diet-induced obese (DIO) mice. Results: Leucine (0.5 mM) exhibited significant synergy with subtherapeutic doses (0.1–10 nM) of PDE5-inhibitors (sildenafil and icariin) on fat oxidation, nitric oxide …