Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits
This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders,...
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| Veröffentlicht in: | International journal of molecular sciences 2025-01, Vol.26 (1), p.364 |
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| creator | Yip, Joyce Mei Xin Chiang, Grace Shu Hui Lee, Ian Chong Jin Lehming-Teo, Rachel Dai, Kexin Dongol, Lokeysh Wang, Laureen Yi-Ting Teo, Denise Seah, Geok Teng Lehming, Norbert |
| description | This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight. |
| doi_str_mv | 10.3390/ijms26010364 |
| format | Article |
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Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms26010364</identifier><identifier>PMID: 39796218</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Aging ; Animals ; Autophagy ; Biosynthesis ; Cancer ; Chronic illnesses ; COVID-19 - metabolism ; COVID-19 - virology ; COVID-19 Drug Treatment ; Diabetes ; Diabetes Mellitus - drug therapy ; Diabetes Mellitus - metabolism ; Disease ; Drug Repositioning - methods ; Drugs ; Enzymes ; Fatty acids ; Glucose ; Homeostasis ; Humans ; Hypoglycemic Agents - pharmacology ; Hypoglycemic Agents - therapeutic use ; Insulin ; Kinases ; Long COVID ; Metabolism ; Metformin - pharmacology ; Metformin - therapeutic use ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - metabolism ; Mitochondrial DNA ; Off-Label Use ; Pancreas ; Peptides ; Phosphorylation ; Proteins ; Quality control ; Review ; SARS-CoV-2 - drug effects ; Senescence</subject><ispartof>International journal of molecular sciences, 2025-01, Vol.26 (1), p.364</ispartof><rights>2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2. Metformin leads to the phosphorylation of the AMP-activated protein kinase AMPK, which accelerates the import of glucose into cells via the glucose transporter GLUT4 and switches the cells to the starvation mode, counteracting the virus. Diabetes drugs also stimulate the unfolded protein response and thus mitophagy, which is beneficial for healthy aging and mental health. Diabetes drugs were also found to mimic exercise and help to reduce body weight.</description><subject>Aging</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Biosynthesis</subject><subject>Cancer</subject><subject>Chronic illnesses</subject><subject>COVID-19 - metabolism</subject><subject>COVID-19 - virology</subject><subject>COVID-19 Drug Treatment</subject><subject>Diabetes</subject><subject>Diabetes Mellitus - drug therapy</subject><subject>Diabetes Mellitus - metabolism</subject><subject>Disease</subject><subject>Drug Repositioning - methods</subject><subject>Drugs</subject><subject>Enzymes</subject><subject>Fatty acids</subject><subject>Glucose</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Insulin</subject><subject>Kinases</subject><subject>Long COVID</subject><subject>Metabolism</subject><subject>Metformin - pharmacology</subject><subject>Metformin - 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| subjects | Aging Animals Autophagy Biosynthesis Cancer Chronic illnesses COVID-19 - metabolism COVID-19 - virology COVID-19 Drug Treatment Diabetes Diabetes Mellitus - drug therapy Diabetes Mellitus - metabolism Disease Drug Repositioning - methods Drugs Enzymes Fatty acids Glucose Homeostasis Humans Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Insulin Kinases Long COVID Metabolism Metformin - pharmacology Metformin - therapeutic use Mitochondria Mitochondria - drug effects Mitochondria - metabolism Mitochondrial DNA Off-Label Use Pancreas Peptides Phosphorylation Proteins Quality control Review SARS-CoV-2 - drug effects Senescence |
| title | Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits |
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