Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Hwang, Sang Mee; Kim, Myungchul; Ji, Shuaifei; Yang, Yeseul; Jeong, Yeji; Kim, Yongbaek

doi:10.1111/cas.13952

Cited by 18 publications

(14 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is possible that the metabolic programs of activated CTLs are unique among adaptive lymphocytes in their generation of oxidized free radicals or endogenous MDR1 transport substrates. Finally, decreased mitochondrial metabolism and increased oxidative stress shown here in MDR1-deficient CTLs resembles that previously described in MDR1-deficient enterocytes, tumor cells, and CD4 + T cells exposed to bile acids in the intestine ( Cao et al, 2017 ; Ho et al, 2018 ; Hwang et al, 2019 ). Thus, it remains possible that a unifying molecular function of MDR1 may eventually be traced to the transport of a common class of endogenous metabolites that is produced by all cells in a manner commensurate with responses to oxidative stress.…”

Section: Resultssupporting

confidence: 83%

Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes

Chen

Sun

Cao

et al. 2020

Journal of Experimental Medicine

View full text Add to dashboard Cite

Multidrug resistance-1 (MDR1) acts as a chemotherapeutic drug efflux pump in tumor cells, although its physiological functions remain enigmatic. Using a recently developed MDR1-knockin reporter allele (Abcb1aAME), we found that constitutive MDR1 expression among hematopoietic cells was observed in cytolytic lymphocytes—including CD8+ cytotoxic T lymphocytes (CTLs) and natural killer cells—and regulated by Runt-related (Runx) transcription factors. Whereas MDR1 was dispensable for naive CD8+ T cell development, it was required for both the normal accumulation of effector CTLs following acute viral infection and the protective function of memory CTLs following challenge with an intracellular bacterium. MDR1 acted early after naive CD8+ T cell activation to suppress oxidative stress, enforce survival, and safeguard mitochondrial function in nascent CTLs. These data highlight an important endogenous function of MDR1 in cell-mediated immune responses and suggest that ongoing efforts to intentionally inhibit MDR1 in cancer patients could be counterproductive.

show abstract

Section: Resultssupporting

confidence: 83%

Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes

Chen

Sun

Cao

et al. 2020

Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…The absorbance measured for untreated control cells was considered representative of 100% cell viability. All other measurements were expressed as the percentage of the control cell value ± standard deviation 26 …”

Section: Methodsmentioning

confidence: 99%

Thyroglobulin as a negative marker for malignancy in canine and human breast tumors

Hwang

Yang

Woo

et al. 2021

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

Canine mammary gland tumors (CMTs) are the most common tumor type in female dogs. This study evaluated the expression pattern and role of thyroglobulin (Tg) in CMT and in human breast cancer (HBC). CMT samples were subjected to fine‐needle aspiration, primary cell culture, and histopathology. The expression level of Tg was higher in benign CMT than in malignant CMT (mCMT) primary cells, particularly in the epithelial lineage. Moreover, treatment with Tg enhanced the sensitivity of doxorubicin in mCMT epithelial cells and mitigated proinflammatory response by increasing nuclear factor erythroid 2‐related factor 2 (Nrf2). The proximal region of the Tg promoter was hypermethylated in mCMT epithelial cells, silencing Tg expression with concurrent downregulation of Nrf2‐mediated antioxidant signaling. An identical pattern of Tg expression was observed in cytological and tissue samples. Tissue microarray analysis showed that Tg was highly expressed in normal and benign tissues when compared with their malignant counterparts, which was diminished along with higher histological grades. The survival rate was significantly higher in HBC patients with high Tg expression than those with low Tg expression. This study also showed that the progression of HBC is accompanied by the reduction of Tg expression along with augmentation of proinflammatory signaling. Our data suggested that Tg could be a negative indicator of malignancy in canine and human breast neoplasia

show abstract

“…Effective blood glucose control was defined as blood glucose levels close to the normal range without severe complications. Ineffectiveness was defined as blood glucose levels that were still high[ 7 , 8 ]. BMD for lumbar vertebra of L1-4 and hip was measured by dual-energy X-ray absorptiometry (Horizon DXA system, Manufacturer: Hologic, Inc., USA, Model: Discovery A) before and after the treatment.…”

Section: Methodsmentioning

confidence: 99%

Effects of different doses of metformin on bone mineral density and bone metabolism in elderly male patients with type 2 diabetes mellitus

Wang

et al. 2020

WJCC

View full text Add to dashboard Cite

BACKGROUND Diabetes is a chronic disease, which may cause various complications. Patients with diabetes are at high risk of bone and joint disorders, such as osteoporosis and bone fractures. In addition, it became widely accepted that diabetes has an important impact on bone metabolism. Metformin is a commonly used and effective first-line treatment for type 2 diabetes. Some glucose-lowering agents have been found to have an effect on bone metabolism. The present study explored if different doses of metformin have an effect on bone mineral density (BMD) and bone metabolism in type 2 diabetes. AIM To investigate the effects of different doses of metformin on BMD and bone metabolism in elderly male patients with type 2 diabetes mellitus. METHODS A total of 120 elderly male outpatients with type 2 diabetes mellitus who were admitted to our hospital were included in the study from July 2018 to June 2019. They were randomly assigned to an experimental group and a control group with 60 patients in each group. Patients in the experimental group were given high dose metformin four times a day 0.5 g each time for 12 wk. Patients in the control group were given low dose metformin orally twice a day 0.5 g each time for 12 wk. The changes in bone mineral density and bone metabolism before and after treatment and the efficacy rate of the treatment were compared between the two groups. RESULTS There was no significant difference in the efficacy rate between the two groups ( P > 0.05). Before the treatment, there was no significant difference in BMD and bone metabolism between the two groups ( P > 0.05). However, after the treatment, BMD and bone metabolism were improved in the two groups. Moreover, BMD and 25-hydroxyvitamin D were significantly higher in the experimental group than in the control group, and N-terminal/midregion and β-isomerized C-terminal telopeptides were significantly lower in the experimental group than in the control group (all P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). CONCLUSION Both high and low dose metformin can effectively control the blood glucose levels in elderly male patients with type 2 diabetes mellitus. However, the benefits of high dose metformin in improving BMD and bone metabolism level was more obvious in patients with type 2 diabetes mellitus.

show abstract

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1

Cited by 18 publications

References 48 publications

Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes

Physiological expression and function of the MDR1 transporter in cytotoxic T lymphocytes

Thyroglobulin as a negative marker for malignancy in canine and human breast tumors

Effects of different doses of metformin on bone mineral density and bone metabolism in elderly male patients with type 2 diabetes mellitus

Contact Info

Product

Resources

About