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

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose‐starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m‐chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.     

Deficient glucose uptake is linked to impaired Glut1 expression upon CD3/CD28 stimulation in memory T cells from pleural effusions secondary to lung cancer

Glucose and nutrient uptake is essential in supporting T cell activation and is increased upon CD3/CD28 stimulation. As T cells from pleural effusions secondary to lung cancer show impaired function, we hypothesized that these cells might have altered expression of nutrient transporters. Here, we analysed by flow cytometry the expression of the transferrin receptor CD71, amino acid transporter CD98 and glucose transporter Glut1 and glucose uptake in pleural effusion‐derived T cells from lung cancer patients, after stimulation via CD3/CD28 under normoxia or hypoxia (2% O₂). We compared the response of T cells from pleural effusions secondary to lung cancer with that of T cells from nonmalignant effusions. In memory T cells from both groups, anti‐CD3/CD28‐stimulation under normoxia upregulated CD98 and CD71 expression (measured as median fluorescence intensity, MFI) in comparison with anti‐CD3‐stimulation. Costimulation under hypoxia tended to increase CD98 expression compared to CD3‐stimulation in memory T cells from both groups. Remarkably, in the cancer group, memory T cells stimulated via CD3/CD28 under hypoxia failed to increase CD71 and Glut1 expression levels compared to the cells receiving anti‐CD3 stimulation, a phenomenon that contrasted with the behaviour of memory T cells from nonmalignant effusions. Consequently, glucose uptake by memory T cells from the cancer group was not increased after CD3/CD28 stimulation under hypoxia, implying that their glycolytic metabolism is defective. As this process is required for inducing an antitumoural response, our study suggests that memory T cells are rendered dysfunctional and are unable to eliminate lung tumour cells.     

Validated RP-HPLC method for quantification of felodipine in rabbit plasma: Application in a bioequivalence study

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Vegetarians have a lower fasting insulin level and higher insulin sensitivity than matched omnivores: A cross-sectional study

Background and aims

Potential associations of vegetarian diet patterns with fasting insulin (FI) and insulin sensitivity remain unclear. We aimed to investigate whether vegetarian diets were associated with FI and insulin sensitivity in a cross-sectional study in Chinese vegetarians and matched omnivores and then to test whether it is independent of body mass index (BMI).

血糖检验中快速血糖仪与常规生化仪的应用

目的比较快速血糖仪与常规生化仪在血糖检验中的价值。方法选择本院224例需要行血糖检验的患者,随机分为观察组和对照组,各112例,每组又根据是否糖尿病患者分为糖尿病患者组和非糖尿病患者组;对照组给予常规生化仪检测,观察组给予快速血糖仪检测,比较两组空腹血糖、餐后2 h血糖。结果观察组与对照组糖尿病患者和非糖尿病空腹血糖、餐后2 h血糖检测水平差异均无统计学意义(P>0.05);观察组检测时间为(0.52±0.21)min,对照组为(32.76±3.45)min,观察组较对照组短(P<0.05)。结论快速血糖仪与常规生化仪进行血糖检验均具有较好的效果,但快速血糖仪更快捷、方便。     

妊娠期糖尿病孕妇血糖和体重控制情况研究

目的探讨系统化血糖及体重控制对妊娠期糖尿病孕妇妊娠结局的影响。方法选择2018年1月-2019年1月中山大学附属第三医院粤东医院收治的100例妊娠期糖尿病孕妇作为研究对象,按护理方式的不同分为观察组和对照组各50例。对照组接受常规治疗及饮食指导干预,观察组在对照组基础上进行系统化血糖和体重控制干预。比较两组孕妇餐前空腹血糖、体重控制情况及母婴并发症发生情况。结果观察组孕妇的血糖及体重控制情况优于对照组,且观察组孕妇及围生儿并发症的发生率低于对照组,差异均有统计学意义(P<0.05)。结论接受系统化血糖及体重控制的妊娠期糖尿病孕妇取得的效果较好,其血糖和体重指数控制较好,母婴并发症少,具有临床推广价值。