Protective effect of pretreatment with propofol against tumor necrosis factor-α-induced hepatic insulin resistance

Zhou, Long; Wang, Lilin; Yang, Baocheng; Zeng, Jinfeng; Zhang, Qingguo; Lei, Hongyi; Xu, Shiyuan

doi:10.3892/etm.2015.2496

Cited by 7 publications

(10 citation statements)

References 38 publications

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“…Propofol has been demonstrated to cause systemic insulin resistance in rats (4). In addition, previous studies have indicated that propofol can induce insulin resistance in mouse primary hepatocytes (5). The molecular mechanism through which propofol influences insulin resistance in mouse primary hepatocytes remains unknown, however the present study focused on PTEN as a potential target for therapeutic intervention to treat the adverse reaction of propofol.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that anesthesia with propofol could induce systemic insulin resistance and decrease insulin-stimulated glucose uptake in skeletal and heart muscles and attenuate the insulin-mediated suppression of hepatic glucose output in rats, however the specific molecular mechanisms underlying this phenomenon remain unknown (4). Previous studies have revealed that propofol can inhibit the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase (GSK)-3b signaling pathway and glycogen synthesis in mouse primary hepatocytes, and the target of propofol-induced insulin resistance in primary mouse hepatocytes was suggested to be upstream of GSK-3β (5). In this study cell viability was assessed by MTT reduction assay, as previously described (5).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have revealed that propofol can inhibit the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase (GSK)-3b signaling pathway and glycogen synthesis in mouse primary hepatocytes, and the target of propofol-induced insulin resistance in primary mouse hepatocytes was suggested to be upstream of GSK-3β (5). In this study cell viability was assessed by MTT reduction assay, as previously described (5). Propofol was added at a final concentration of 10 µg/ml, based on the results of previous studies (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

“…In this study cell viability was assessed by MTT reduction assay, as previously described (5). Propofol was added at a final concentration of 10 µg/ml, based on the results of previous studies (5)(6)(7)(8). PTEN is an important regulatory gene of the PI3K/Akt/GSK-3β signaling pathway (9)(10)(11), and inhibition of PTEN activity can activate the Akt signal transduction pathway (12).…”

Section: Introductionmentioning

confidence: 99%

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PTEN in propofol‑induced insulin resistance in mouse primary hepatocytes

et al. 2018

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Propofol is the most common intravenous anesthetic agent used in clinical practice. Propofol can induce insulin resistance in mouse primary hepatocytes, however the molecular mechanism through which propofol acts remains largely unknown. Based on previous studies, it was hypothesized that phosphatase and tensin homolog (PTEN) is involved in propofol-mediated insulin resistance. The aim of the present study was to investigate the biological function of PTEN and its molecular mechanism in propofol-induced insulin resistance in mouse primary hepatocytes. Mouse primary hepatocytes were treated with propofol and transfected with small interfering RNA (siRNA)-996 to silence the endogenous expression of PTEN. The current study assessed the effects of propofol and PTEN knockdown on the expression of PTEN and several key enzymes of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase-3β signaling pathway, as well as the glycogen content in mouse primary hepatocytes. Treatment with propofol significantly increased protein and mRNA PTEN expression in mouse primary hepatocytes. In addition, knockdown of PTEN reversed propofol-induced insulin resistance in mouse primary hepatocytes. The present study indicated that PTEN serves a role in the physiological process of propofol-induced insulin resistance in mouse primary hepatocytes, and PTEN inhibition may be a potential target for therapeutic intervention against propofol-induced adverse effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PTEN in propofol‑induced insulin resistance in mouse primary hepatocytes

et al. 2018

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“…Insulin resistance (IR) results from impaired glucose metabolism, and is characterized by a decreased sensitivity of target organs to insulin. IR is one of the most common and serious perioperative complications and is frequently associated with a longer hospital stay, increased susceptibility to infection, and higher risk of mortality [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine alleviates insulin resistance in hepatocytes by reducing endoplasmic reticulum stress

Liu

Zhu

et al. 2019

Endocrine

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Purpose Dexmedetomidine (DEX) stabilizes intraoperative blood glucose levels and reduces insulin resistance (IR), a common perioperative complication. However, the molecular mechanisms underlying these effects remain unclear. Since endoplasmic reticulum stress (ERS) is a mechanism of IR, this study sought to examine whether DEX can effectively alleviate IR by reducing ERS. Methods HepG2 and LO2 cells were treated with different concentrations of insulin. The glucose content assay and Cell Counting Kit-8 (CCK-8) were then employed to determine the optimal insulin concentration capable of inducing IR without affecting cell viability. Insulin-resistant hepatocytes were cultured with different concentrations of DEX for 24 h, and the glucose concentration in the supernatant was measured. ERS was assessed by qPCR and western blotting. The latter was also used to quantify the expression of phosphorylated protein kinase B (p-AKT), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6 phosphatase (G6Pase), which are key proteins involved in the action of insulin. Results After 48-h of culturing with 10 μg/mL insulin, glucose consumption in hepatocytes was found to be reduced. IR hepatocytes cultured with 10, 100, or 1000 ng/ml DEX for 24 h showed a concentration-dependent increase in glucose consumption. Elevated mRNA and protein levels of ERS markers binding immunoglobulin protein (BIP) and ER protein 29 (ERp29), were reversed by DEX treatment. Moreover, reduced p-AKT and increased PEPCK and G6Pase protein levels in IR hepatocytes were also restored following DEX treatment. Conclusion DEX may alleviate IR in hepatocytes by reducing ERS serving to restore insulin action via the IRS-1/PI3K/AKT pathway.

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Investigation of insulin resistance through a multiorgan microfluidic organ-on-chip

Tanataweethum¹,

Trang²,

Lee³

et al. 2022

Biomed. Mater.

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The development of hepatic insulin resistance (IR) is a critical factor in developing type 2 diabetes (T2D), where insulin fails to inhibit hepatic glucose production but retains its capacity to promote hepatic lipogenesis. Improving insulin sensitivity can be effective in preventing and treating T2D. However, selective control of glucose and lipid synthesis has been difficult. It is known that excess white adipose tissue is detrimental to insulin sensitivity, whereas brown adipose tissue transplantation can restore it in diabetic mice. However, challenges remain in our understanding of liver-adipose communication because the confounding effects of hypothalamic regulation of metabolic function cannot be ruled out in previous studies. There is a lack of in vitro models that use primary cells to study cellular-crosstalk under insulin resistant conditions. Building upon our previous work on the microfluidic primary liver and adipose organ-on-chips, we report for the first time the development of integrated insulin resistant liver-adipose (white and brown) organ-on-chip. The design of the microfluidic device was carried out using computational fluid dynamics; the experimental studies were conducted by carrying out detailed biochemical analysis RNA-seq analysis on both cell types. Further, we tested the hypothesis that brown adipocytes regulated both hepatic insulin sensitivity and lipogenesis. Our results show effective co-modulation of hepatic glucose and lipid synthesis through a platform for identifying potential therapeutics for IR and diabetes.

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Protective effect of pretreatment with propofol against tumor necrosis factor-α-induced hepatic insulin resistance

Cited by 7 publications

References 38 publications

PTEN in propofol‑induced insulin resistance in mouse primary hepatocytes

PTEN in propofol‑induced insulin resistance in mouse primary hepatocytes

Dexmedetomidine alleviates insulin resistance in hepatocytes by reducing endoplasmic reticulum stress

Investigation of insulin resistance through a multiorgan microfluidic organ-on-chip

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