Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.
Level 5 - mechanism / opinion, no new human data
Preclinical animal (mouse) and in vitro cell culture study with no human data
PubMed 28358805 · doi:10.1371/journal.pbio.2001951
What was done
Investigators evaluated how glucose availability and hyperglycemia-inducing cancer medications (dexamethasone and rapamycin) influence doxorubicin (DXR) toxicity in yeast, cultured cardiomyocytes, and mouse models. They examined the impact of fasting, glucose restriction, insulin, and glucose administration on doxorubicin-induced cardiotoxicity and characterized the downstream regulatory pathway involving PKA, AMPK, early growth response protein 1 (EGR1), and cardioprotective peptides (ANP and BNP).
What was found
The abstract reports directional findings without numerical values. Dexamethasone and rapamycin elevated glucose and sensitized cardiomyocytes and mice to doxorubicin. Reducing circulating glucose via fasting or insulin reversed this toxicity, while direct glucose injections negated fasting-mediated protection. Fasting or glucose restriction regulated PKA and AMPK activity, activated EGR1, and increased cardiac expression of ANP and BNP.
Why it matters
The study outlines a conserved glucose-PKA-EGR1 signaling axis that modulates toxin resistance and suggests that drug-induced hyperglycemia may heighten chemotherapy-related cardiotoxicity, pointing toward dietary or glycemic management as potential protective strategies.
Limits
Findings are restricted to preclinical laboratory and animal models and lack human validation. The abstract reports no quantitative values, effect sizes, variance measures, or sample sizes. The impact of glucose manipulation on tumor response to chemotherapy is not detailed in the abstract.
Cited by
- supports In mammalian cells, glucose levels directly activate Protein Kinase A (PKA).