Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity
Antje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB), acts syner...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2013-02-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Online Access: | http://www.dovepress.com/synergistic-effects-of-metformin-resveratrol-and-hydroxymethylbutyrate-a12205 |
| _version_ | 1797936053605105664 |
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| author | Bruckbauer A Zemel MB |
| author_facet | Bruckbauer A Zemel MB |
| author_sort | Bruckbauer A |
| collection | DOAJ |
| description | Antje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB), acts synergistically with low doses of metformin to impact insulin sensitivity and AMP-activated protein kinase-dependent outcomes in cell culture and in diabetic mice.Methods: C2C12 skeletal myotubes and 3T3-L1 adipocytes were treated with resveratrol 0.2 µM, HMB 5 µM, and metformin 0.1 mM alone or in combination. db/db mice were treated for 2 weeks with high (1.5 g/kg diet), low (0.75 g/kg diet), or very low (0.25 g/kg diet) doses of metformin alone or in combination with a diet containing resveratrol 12.5 mg and CaHMB 2 g/kg.Results: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone. A similar trend was found in 3T3L1 adipocytes. In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMAIR), plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. In addition, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice.Conclusion: Resveratrol-HMB combined with metformin may act synergistically on AMP-activated protein kinase-dependent pathways, leading to increased insulin sensitivity, which may reduce the therapeutic doses of metformin necessary in the treatment of diabetes.Keywords: diabetes, AMP-activated protein kinase, Sirt1, fat oxidation |
| first_indexed | 2024-04-10T18:23:39Z |
| format | Article |
| id | doaj.art-a2d3d707b67948648c485fb43491b6b4 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T18:23:39Z |
| publishDate | 2013-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-a2d3d707b67948648c485fb43491b6b42023-02-02T06:44:28ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072013-02-012013default93102Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivityBruckbauer AZemel MBAntje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB), acts synergistically with low doses of metformin to impact insulin sensitivity and AMP-activated protein kinase-dependent outcomes in cell culture and in diabetic mice.Methods: C2C12 skeletal myotubes and 3T3-L1 adipocytes were treated with resveratrol 0.2 µM, HMB 5 µM, and metformin 0.1 mM alone or in combination. db/db mice were treated for 2 weeks with high (1.5 g/kg diet), low (0.75 g/kg diet), or very low (0.25 g/kg diet) doses of metformin alone or in combination with a diet containing resveratrol 12.5 mg and CaHMB 2 g/kg.Results: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone. A similar trend was found in 3T3L1 adipocytes. In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMAIR), plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. In addition, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice.Conclusion: Resveratrol-HMB combined with metformin may act synergistically on AMP-activated protein kinase-dependent pathways, leading to increased insulin sensitivity, which may reduce the therapeutic doses of metformin necessary in the treatment of diabetes.Keywords: diabetes, AMP-activated protein kinase, Sirt1, fat oxidationhttp://www.dovepress.com/synergistic-effects-of-metformin-resveratrol-and-hydroxymethylbutyrate-a12205 |
| spellingShingle | Bruckbauer A Zemel MB Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity Diabetes, Metabolic Syndrome and Obesity |
| title | Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity |
| title_full | Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity |
| title_fullStr | Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity |
| title_full_unstemmed | Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity |
| title_short | Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity |
| title_sort | synergistic effects of metformin resveratrol and hydroxymethylbutyrate on insulin sensitivity |
| url | http://www.dovepress.com/synergistic-effects-of-metformin-resveratrol-and-hydroxymethylbutyrate-a12205 |
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