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Health & Wellness
Metformin Weight Loss Combo: Effect of Leucine plus Metformin and Sildenafil Combination
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<blockquote data-quote="Nelson Vergel" data-source="post: 133270" data-attributes="member: 3"><p>Metabolism. 2015 Jul;64(7):845-56. doi: 10.1016/j.metabol.2015.03.007. Epub 2015 Mar 19</p><p></p><p><strong><span style="font-size: 15px">Leucine amplifies the effects of metformin on insulin sensitivity and glycemic control in diet-induced obese mice</span></strong></p><p>Fu L1, Bruckbauer A2, Li F1, Cao Q1, Cui X1, Wu R1, Shi H1, Zemel MB2, Xue B3.</p><p></p><p>Abstract</p><p>BACKGROUND AND OBJECTIVE:</p><p>The Sirt1/AMPK signaling pathway is a key sensor of energy status and regulates glucose and lipid metabolism. Leucine (Leu) activates Sirt1 by lowering its Km for NAD(+) and potentiates other sirtuin/AMPK-activators, resulting in improvement of insulin sensitivity. Since metformin (Met) converges on this pathway, we hypothesized that leucine would amplify its gluco-regulatory effects.</p><p></p><p>MATERIALS AND METHODS:</p><p>The effects of Leu (24 g/kg diet)+Met (0.05-0.5 g/kg diet) combinations were compared to standard therapeutic Met (1.5 g/kg diet; ~300 mg/kg BW) on glycemic control in high fat diet induced insulin resistant mice for 6 weeks. The effects of Leu on Met stimulation of Sirt1 and AMPK activities were further evaluated in adipocytes.</p><p></p><p>RESULTS:</p><p>Sub-therapeutic levels of Met combined with Leu resulted in increases in Sirt1 activity and in tissue P-AMPK/AMPK ratio and corresponding dose-responsive improvements in fasting and post-prandial glucose, in glucose response to an insulin tolerance test and in the area under the curve in glucose tolerance tests. Changes were evident within 7 days of treatment and sustained throughout the 6-week study duration. The Leu+Met (0.25 g/kg)-combinations produced a comparable effect to a standard therapeutic Met dose, while the Leu+Met (0.5 g/kg diet) resulted in greater improvements. Since resveratrol also synergizes with leucine to augment sirtuin signaling and insulin sensitivity, we tested the addition of resveratrol to Leu-Met and found no additional benefit.</p><p></p><p>CONCLUSION:</p><p>These data demonstrate that adding Leu to Met enables a dose reduction of 66% with improved efficacy and of 83% with comparable efficacy to standard metformin in diet-induced obese mice, and addition of resveratrol does not provide further benefit.</p></blockquote><p></p>
[QUOTE="Nelson Vergel, post: 133270, member: 3"] Metabolism. 2015 Jul;64(7):845-56. doi: 10.1016/j.metabol.2015.03.007. Epub 2015 Mar 19 [B][SIZE=15px]Leucine amplifies the effects of metformin on insulin sensitivity and glycemic control in diet-induced obese mice[/SIZE][/B] Fu L1, Bruckbauer A2, Li F1, Cao Q1, Cui X1, Wu R1, Shi H1, Zemel MB2, Xue B3. Abstract BACKGROUND AND OBJECTIVE: The Sirt1/AMPK signaling pathway is a key sensor of energy status and regulates glucose and lipid metabolism. Leucine (Leu) activates Sirt1 by lowering its Km for NAD(+) and potentiates other sirtuin/AMPK-activators, resulting in improvement of insulin sensitivity. Since metformin (Met) converges on this pathway, we hypothesized that leucine would amplify its gluco-regulatory effects. MATERIALS AND METHODS: The effects of Leu (24 g/kg diet)+Met (0.05-0.5 g/kg diet) combinations were compared to standard therapeutic Met (1.5 g/kg diet; ~300 mg/kg BW) on glycemic control in high fat diet induced insulin resistant mice for 6 weeks. The effects of Leu on Met stimulation of Sirt1 and AMPK activities were further evaluated in adipocytes. RESULTS: Sub-therapeutic levels of Met combined with Leu resulted in increases in Sirt1 activity and in tissue P-AMPK/AMPK ratio and corresponding dose-responsive improvements in fasting and post-prandial glucose, in glucose response to an insulin tolerance test and in the area under the curve in glucose tolerance tests. Changes were evident within 7 days of treatment and sustained throughout the 6-week study duration. The Leu+Met (0.25 g/kg)-combinations produced a comparable effect to a standard therapeutic Met dose, while the Leu+Met (0.5 g/kg diet) resulted in greater improvements. Since resveratrol also synergizes with leucine to augment sirtuin signaling and insulin sensitivity, we tested the addition of resveratrol to Leu-Met and found no additional benefit. CONCLUSION: These data demonstrate that adding Leu to Met enables a dose reduction of 66% with improved efficacy and of 83% with comparable efficacy to standard metformin in diet-induced obese mice, and addition of resveratrol does not provide further benefit. [/QUOTE]
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Metformin Weight Loss Combo: Effect of Leucine plus Metformin and Sildenafil Combination
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