The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with obesity and excessive fat accumulation in the liver and pancreas leading to insulin resistance and hyperglycemia. While lifestyle modifications are the first-line approach to managing T2DM, many patients require...
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Elsevier
2025-03-01
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| Series: | Results in Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211715625001225 |
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| author | Mighty Kemelo Phillip Moseki |
| author_facet | Mighty Kemelo Phillip Moseki |
| author_sort | Mighty Kemelo |
| collection | DOAJ |
| description | Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with obesity and excessive fat accumulation in the liver and pancreas leading to insulin resistance and hyperglycemia. While lifestyle modifications are the first-line approach to managing T2DM, many patients require oral hypoglycemic medications to regulate and maintain blood glucose levels. Although the precise mechanisms of action for these drugs remain unclear, emerging evidence suggests that they may exert their effects through the AMP-activated protein kinase (AMPK) and/or Sirtuin 1 (SIRT1) pathways. Activation of the AMPK pathway promotes fatty acid oxidation, suppresses cholesterol biosynthesis, and enhances glucose uptake. Similarly, SIRT1, an NAD+-dependent deacetylase, regulates many proteins involved in glucose homeostasis and insulin signaling. This review explores the therapeutic potential of AMPK and SIRT1 in T2DM. It provides an in-depth analysis of AMPK's role in T2DM pathogenesis and highlights the benefits of AMPK modulation by polyphenols. Additionally, it delves into the mechanisms of oral hypoglycemic drugs, emphasizing the significance of AMPK activation. Furthermore, the review discusses the impact of calorie restriction and SIRT1 activation in T2DM, considering both non-pharmacological interventions and synthetic SIRT1 activation as viable therapeutic options. |
| format | Article |
| id | doaj-art-9abcc23786c84ee789e4c294dbb889ca |
| institution | DOAJ |
| issn | 2211-7156 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Results in Chemistry |
| spelling | doaj-art-9abcc23786c84ee789e4c294dbb889ca2025-08-20T02:47:39ZengElsevierResults in Chemistry2211-71562025-03-011410213910.1016/j.rechem.2025.102139The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus managementMighty Kemelo0Phillip Moseki1Department of Biomedical Sciences, Faculty of Medicine, University of Botswana, Botswana; Corresponding author at: Department of Biomedical Sciences, Faculty of Medicine, University of Botswana, Botswana.Department of Biological Sciences, Faculty of Science, University of Botswana, BotswanaType 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly associated with obesity and excessive fat accumulation in the liver and pancreas leading to insulin resistance and hyperglycemia. While lifestyle modifications are the first-line approach to managing T2DM, many patients require oral hypoglycemic medications to regulate and maintain blood glucose levels. Although the precise mechanisms of action for these drugs remain unclear, emerging evidence suggests that they may exert their effects through the AMP-activated protein kinase (AMPK) and/or Sirtuin 1 (SIRT1) pathways. Activation of the AMPK pathway promotes fatty acid oxidation, suppresses cholesterol biosynthesis, and enhances glucose uptake. Similarly, SIRT1, an NAD+-dependent deacetylase, regulates many proteins involved in glucose homeostasis and insulin signaling. This review explores the therapeutic potential of AMPK and SIRT1 in T2DM. It provides an in-depth analysis of AMPK's role in T2DM pathogenesis and highlights the benefits of AMPK modulation by polyphenols. Additionally, it delves into the mechanisms of oral hypoglycemic drugs, emphasizing the significance of AMPK activation. Furthermore, the review discusses the impact of calorie restriction and SIRT1 activation in T2DM, considering both non-pharmacological interventions and synthetic SIRT1 activation as viable therapeutic options.http://www.sciencedirect.com/science/article/pii/S2211715625001225Type 2 diabetes mellitus (T2DM)Natural polyphenolsAMP-activated protein kinase (AMPK)Oral hypoglycemic drugsSirtuin-1 (SIRT1)Sirtuin-activating compounds (STACs) |
| spellingShingle | Mighty Kemelo Phillip Moseki The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management Results in Chemistry Type 2 diabetes mellitus (T2DM) Natural polyphenols AMP-activated protein kinase (AMPK) Oral hypoglycemic drugs Sirtuin-1 (SIRT1) Sirtuin-activating compounds (STACs) |
| title | The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management |
| title_full | The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management |
| title_fullStr | The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management |
| title_full_unstemmed | The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management |
| title_short | The AMPK-SIRT1 Axis: Redefining type 2 diabetes mellitus management |
| title_sort | ampk sirt1 axis redefining type 2 diabetes mellitus management |
| topic | Type 2 diabetes mellitus (T2DM) Natural polyphenols AMP-activated protein kinase (AMPK) Oral hypoglycemic drugs Sirtuin-1 (SIRT1) Sirtuin-activating compounds (STACs) |
| url | http://www.sciencedirect.com/science/article/pii/S2211715625001225 |
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