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Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity
BACKGROUND: 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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575126/ https://www.ncbi.nlm.nih.gov/pubmed/23430507 http://dx.doi.org/10.2147/DMSO.S40840 |
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author | Bruckbauer, Antje Zemel, Michael B |
author_facet | Bruckbauer, Antje Zemel, Michael B |
author_sort | Bruckbauer, Antje |
collection | PubMed |
description | BACKGROUND: 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 (HOMA(IR)), 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. |
format | Online Article Text |
id | pubmed-3575126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35751262013-02-21 Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity Bruckbauer, Antje Zemel, Michael B Diabetes Metab Syndr Obes Original Research BACKGROUND: 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 (HOMA(IR)), 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. Dove Medical Press 2013-02-13 /pmc/articles/PMC3575126/ /pubmed/23430507 http://dx.doi.org/10.2147/DMSO.S40840 Text en © 2013 Bruckbauer and Zemel, publisher and licensee Dove Medical Press Ltd This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. |
spellingShingle | Original Research Bruckbauer, Antje Zemel, Michael B Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity |
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 |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3575126/ https://www.ncbi.nlm.nih.gov/pubmed/23430507 http://dx.doi.org/10.2147/DMSO.S40840 |
work_keys_str_mv | AT bruckbauerantje synergisticeffectsofmetforminresveratrolandhydroxymethylbutyrateoninsulinsensitivity AT zemelmichaelb synergisticeffectsofmetforminresveratrolandhydroxymethylbutyrateoninsulinsensitivity |