Increasing interest in repurposing the diabetic medication metformin for cancer treatment has raised important questions about the translation of promising preclinical findings to therapeutic efficacy, especially in non-diabetic patients. A significant limitation of the findings to date is the use of supraphysiologic metformin doses and hyperglycemic conditions in vitro. Our goals were to determine the impact of hyperglycemia on metformin response and to address the applicability of metformin as a cancer therapeutic in non-diabetic patients. In normoglycemic conditions, lower concentrations of metformin were required to inhibit cell viability, while metformin treatment in hyperglycemic conditions resulted in increased glucose uptake and glycolytic flux, contributing to cell survival. Mechanistically, maintenance of c-Myc expression under conditions of hyperglycemia or via gene amplification facilitated metabolic escape from the effects of metformin. In vivo, treatment of an ovarian cancer mouse model with metformin resulted in greater tumor weight reduction in normoglycemic vs. hyperglycemic mice, with increased c-Myc expression observed in metformin-treated hyperglycemic mice. These findings indicate that hyperglycemia inhibits the anti-cancer effects of metformin in vitro and in vivo. Furthermore, our results suggest that metformin may elicit stronger responses in normoglycemic vs. hyperglycemic patients, highlighting the need for prospective clinical testing in patients without diabetes.
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http://dx.doi.org/10.18632/oncotarget.4556 | DOI Listing |
Metab Brain Dis
December 2024
Department of Basic Science, School of Science and Technology, Babcock University, Ilishan-Remo, Ogun State, Nigeria.
Diabetes Mellitus is a metabolic disorder characterized by high blood glucose levels, causing significant morbidity and mortality rates. This study investigated the antidiabetic, neuroprotective, and antioxidant effects of ethanol extracts of Parkia biglobosa (PB) leaves and seeds in streptozotocin (STZ)-induced diabetic rats. The administration of STZ significantly elevated fasting blood glucose levels (FBGL) to 355-400 mg/mL compared to 111 mg/mL in normal controls, indicating hyperglycemia.
View Article and Find Full Text PDFSAGE Open Med
December 2024
Department of Endocrinology, Diabetology, and Internal Medicine, Tahar Sfar University Hospital, Mahdia, Tunisia.
Introduction: Polycystic ovary syndrome is a common chronic condition characterized by insulin resistance and hyperandrogenism, leading to significant health risks and impaired quality of life. Sodium-glucose transporter type 2 inhibitors have shown promise in improving the metabolic profile of women with polycystic ovary syndrome. However, their impact on hormonal parameters and cycle disorders remains uncertain.
View Article and Find Full Text PDFBackground Diabetes mellitus, characterized by chronic hyperglycemia, often leads to severe hepatic dysfunction, including increased liver enzyme levels and histopathological changes in the liver. Streptozotocin (STZ)-induced diabetic rat models provide a valuable method for evaluating potential therapeutic agents that target hepatic complications. , a medicinal plant with known anti-diabetic properties, has been used traditionally for its hepatoprotective effects, although scientific evidence is limited.
View Article and Find Full Text PDFJ Diabetes Metab Disord
June 2025
Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, 16 Dingxiang Road, Changzhou, 213000 China.
Objectives: The changes in amino acid (AA) levels have been observed in pregnant women with gestational diabetes mellitus (GDM). However, it remains unclear whether the AA levels in offspring of GDM mothers are affected by GDM. This study aimed to investigate the changes in AA metabolism in offspring of pregnant women with GDM undergoing different glycemic control treatment regimens.
View Article and Find Full Text PDFDiabetes Metab Syndr Obes
December 2024
Global Research & Development Medical - MU CM&E, Merck Healthcare KGaA, Darmstadt, Germany.
Prediabetes is the first stage of a continuum that extends through the diagnosis of clinical type 2 diabetes towards long-standing diabetes with multiple comorbidities. The diagnosis of prediabetes provides an opportunity to interrupt the diabetes continuum at an early stage to ensure long-term optimization of clinical outcomes. All people with prediabetes should receive intervention to improve their lifestyles (quality of diet and level of physical activity), as this has been proven beyond doubt to reduce substantially the risk of conversion to diabetes.
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