Tamoxifen treatment causes early hepatic insulin resistance

Klöting, Nora; Kern, Matthias; Moruzzi, Michele; Stümvoll, Michael; Blüher, Matthias

doi:10.1007/s00592-019-01468-6

Cited by 6 publications

(9 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hepatic steatosis in rodents and a decrease in pancreatic ß-cell survival and proliferation have been attributed to this potential adverse effect (42). Klöting et al (41) in-vivo study demonstrated that upon administration tamoxifen caused approximately 75% loss of body fat followed by a phase of weight gain within the first weeks. The weight regain led to the accumulation of ectopic fat and the development of fatty liver.…”

Section: Chemotherapeutic Agentsmentioning

confidence: 99%

“…( 77 ) analyzed risk factors associated with doxorubicin-induced hyperglycemia in patients, and in this study, it was found, the risk of hyperglycemia was increased further by using corticosteroids. Tamoxifen is a highly lipophilic chemotherapeutic agent which exerts its anticancer effects by inducing apoptosis and oxidative stress via mechanisms that involve the mitochondria ( 41 , 42 ). High concentrations of tamoxifen between 20 to 100µmol/L inhibited mitochondrial permeability transition pore opening in isolated rat liver mitochondria ( 41 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…Tamoxifen is a highly lipophilic chemotherapeutic agent which exerts its anticancer effects by inducing apoptosis and oxidative stress via mechanisms that involve the mitochondria ( 41 , 42 ). High concentrations of tamoxifen between 20 to 100µmol/L inhibited mitochondrial permeability transition pore opening in isolated rat liver mitochondria ( 41 ). Additionally, these high concentrations increased mitochondrial respiration by disrupting the mitochondrial membrane integrity and decreased oxidative phosphorylation and mitochondrial transmembrane potential (Δ ψ ) ( 41 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…High concentrations of tamoxifen between 20 to 100µmol/L inhibited mitochondrial permeability transition pore opening in isolated rat liver mitochondria ( 41 ). Additionally, these high concentrations increased mitochondrial respiration by disrupting the mitochondrial membrane integrity and decreased oxidative phosphorylation and mitochondrial transmembrane potential (Δ ψ ) ( 41 ). Tamoxifen has been reported to increase the incidence of diabetes mellitus ( 41 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

“…Additionally, these high concentrations increased mitochondrial respiration by disrupting the mitochondrial membrane integrity and decreased oxidative phosphorylation and mitochondrial transmembrane potential (Δ ψ ) ( 41 ). Tamoxifen has been reported to increase the incidence of diabetes mellitus ( 41 ). Hepatic steatosis in rodents and a decrease in pancreatic ß-cell survival and proliferation have been attributed to this potential adverse effect ( 42 ).…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

See 4 more Smart Citations

Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments

et al. 2023

View full text Add to dashboard Cite

Mitochondrial impairment has been associated with the development of insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM). However, the relationship between mitochondrial impairment and insulin resistance is not fully elucidated due to insufficient evidence to support the hypothesis. Insulin resistance and insulin deficiency are both characterised by excessive production of reactive oxygen species and mitochondrial coupling. Compelling evidence states that improving the function of the mitochondria may provide a positive therapeutic tool for improving insulin sensitivity. There has been a rapid increase in reports of the toxic effects of drugs and pollutants on the mitochondria in recent decades, interestingly correlating with an increase in insulin resistance prevalence. A variety of drug classes have been reported to potentially induce toxicity in the mitochondria leading to skeletal muscle, liver, central nervous system, and kidney injury. With the increase in diabetes prevalence and mitochondrial toxicity, it is therefore imperative to understand how mitochondrial toxicological agents can potentially compromise insulin sensitivity. This review article aims to explore and summarise the correlation between potential mitochondrial dysfunction caused by selected pharmacological agents and its effect on insulin signalling and glucose handling. Additionally, this review highlights the necessity for further studies aimed to understand drug-induced mitochondrial toxicity and the development of insulin resistance.

show abstract

Section: Chemotherapeutic Agentsmentioning

confidence: 99%

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

See 3 more Smart Citations

Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments

et al. 2023

View full text Add to dashboard Cite

show abstract

The ethanolic extract of Aframomum angustifolium seeds protects against tamoxifen-induced side effects in rats with breast cancer

Makamwe,

Ntentie,

Mbong

et al. 2023

ADV TRADIT MED (ADTM)

View full text Add to dashboard Cite

Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures

Lee,

Xue,

et al. 2024

Transl Psychiatry

View full text Add to dashboard Cite

Antipsychotic (AP)-naive first-episode psychosis (FEP) patients display early dysglycemia, including insulin resistance and prediabetes. Metabolic dysregulation may therefore be intrinsic to psychosis spectrum disorders (PSDs), independent of the metabolic effects of APs. However, the potential biological pathways that overlap between PSDs and dysglycemic states remain to be identified. Using meta-analytic approaches of transcriptomic datasets, we investigated whether AP-naive FEP patients share overlapping gene expression signatures with non-psychiatrically ill early dysglycemia individuals. We meta-analyzed peripheral transcriptomic datasets of AP-naive FEP patients and non-psychiatrically ill early dysglycemia subjects to identify common gene expression signatures. Common signatures underwent pathway enrichment analysis and were then used to identify potential new pharmacological compounds via Integrative Library of Integrated Network-Based Cellular Signatures (iLINCS). Our search results yielded 5 AP-naive FEP studies and 4 early dysglycemia studies which met inclusion criteria. We discovered that AP-naive FEP and non-psychiatrically ill subjects exhibiting early dysglycemia shared 221 common signatures, which were enriched for pathways related to endoplasmic reticulum stress and abnormal brain energetics. Nine FDA-approved drugs were identified as potential drug treatments, of which the antidiabetic metformin, the first-line treatment for type 2 diabetes, has evidence to attenuate metabolic dysfunction in PSDs. Taken together, our findings support shared gene expression changes and biological pathways associating PSDs with dysglycemic disorders. These data suggest that the pathobiology of PSDs overlaps and potentially contributes to dysglycemia. Finally, we find that metformin may be a potential treatment for early metabolic dysfunction intrinsic to PSDs.

show abstract

Tamoxifen treatment causes early hepatic insulin resistance

Cited by 6 publications

References 5 publications

Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments

Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments

The ethanolic extract of Aframomum angustifolium seeds protects against tamoxifen-induced side effects in rats with breast cancer

Glucose dysregulation in antipsychotic-naive first-episode psychosis: in silico exploration of gene expression signatures

Contact Info

Product

Resources

About