Targeting the Metabolic Paradigms in Cancer and Diabetes
Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/1/211 |
| _version_ | 1797340034204958720 |
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| author | Mira Bosso Dania Haddad Ashraf Al Madhoun Fahd Al-Mulla |
| author_facet | Mira Bosso Dania Haddad Ashraf Al Madhoun Fahd Al-Mulla |
| author_sort | Mira Bosso |
| collection | DOAJ |
| description | Dysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS–glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios. |
| first_indexed | 2024-03-08T09:57:05Z |
| format | Article |
| id | doaj.art-ac445cc20c3b4d1a91e1551cf4c44015 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-08T09:57:05Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-ac445cc20c3b4d1a91e1551cf4c440152024-01-29T13:47:54ZengMDPI AGBiomedicines2227-90592024-01-0112121110.3390/biomedicines12010211Targeting the Metabolic Paradigms in Cancer and DiabetesMira Bosso0Dania Haddad1Ashraf Al Madhoun2Fahd Al-Mulla3Department of Pathology, Faculty of Medicine, Health Science Center, Kuwait University, Safat 13110, KuwaitDepartment of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Genetics and Bioinformatics, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Pathology, Faculty of Medicine, Health Science Center, Kuwait University, Safat 13110, KuwaitDysregulated metabolic dynamics are evident in both cancer and diabetes, with metabolic alterations representing a facet of the myriad changes observed in these conditions. This review delves into the commonalities in metabolism between cancer and type 2 diabetes (T2D), focusing specifically on the contrasting roles of oxidative phosphorylation (OXPHOS) and glycolysis as primary energy-generating pathways within cells. Building on earlier research, we explore how a shift towards one pathway over the other serves as a foundational aspect in the development of cancer and T2D. Unlike previous reviews, we posit that this shift may occur in seemingly opposing yet complementary directions, akin to the Yin and Yang concept. These metabolic fluctuations reveal an intricate network of underlying defective signaling pathways, orchestrating the pathogenesis and progression of each disease. The Warburg phenomenon, characterized by the prevalence of aerobic glycolysis over minimal to no OXPHOS, emerges as the predominant metabolic phenotype in cancer. Conversely, in T2D, the prevailing metabolic paradigm has traditionally been perceived in terms of discrete irregularities rather than an OXPHOS-to-glycolysis shift. Throughout T2D pathogenesis, OXPHOS remains consistently heightened due to chronic hyperglycemia or hyperinsulinemia. In advanced insulin resistance and T2D, the metabolic landscape becomes more complex, featuring differential tissue-specific alterations that affect OXPHOS. Recent findings suggest that addressing the metabolic imbalance in both cancer and diabetes could offer an effective treatment strategy. Numerous pharmaceutical and nutritional modalities exhibiting therapeutic effects in both conditions ultimately modulate the OXPHOS–glycolysis axis. Noteworthy nutritional adjuncts, such as alpha-lipoic acid, flavonoids, and glutamine, demonstrate the ability to reprogram metabolism, exerting anti-tumor and anti-diabetic effects. Similarly, pharmacological agents like metformin exhibit therapeutic efficacy in both T2D and cancer. This review discusses the molecular mechanisms underlying these metabolic shifts and explores promising therapeutic strategies aimed at reversing the metabolic imbalance in both disease scenarios.https://www.mdpi.com/2227-9059/12/1/211oxidative phosphorylationcancermitochondriametabolic shifttype 2 diabetesinsulin resistance |
| spellingShingle | Mira Bosso Dania Haddad Ashraf Al Madhoun Fahd Al-Mulla Targeting the Metabolic Paradigms in Cancer and Diabetes Biomedicines oxidative phosphorylation cancer mitochondria metabolic shift type 2 diabetes insulin resistance |
| title | Targeting the Metabolic Paradigms in Cancer and Diabetes |
| title_full | Targeting the Metabolic Paradigms in Cancer and Diabetes |
| title_fullStr | Targeting the Metabolic Paradigms in Cancer and Diabetes |
| title_full_unstemmed | Targeting the Metabolic Paradigms in Cancer and Diabetes |
| title_short | Targeting the Metabolic Paradigms in Cancer and Diabetes |
| title_sort | targeting the metabolic paradigms in cancer and diabetes |
| topic | oxidative phosphorylation cancer mitochondria metabolic shift type 2 diabetes insulin resistance |
| url | https://www.mdpi.com/2227-9059/12/1/211 |
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