Suppression of ROS Production by Exendin-4 in PSC Attenuates the High Glucose-Induced Islet Fibrosis

Kim, Ji-Won; Park, Shin-Young; You, Young-Hye; Ham, Dong-Sik; Lee, Seung‐Hwan; Yang, Hae Kyung; Jeong, In‐Kyung; Ko, Seung‐Hyun; Yoon, Kun‐Ho

doi:10.1371/journal.pone.0163187

Cited by 22 publications

(20 citation statements)

References 28 publications

(40 reference statements)

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“…13 Another work reported that HG condition interrupts tissue and cell function through inhibiting certain gene functions by changing its expression, synthesis and degradation. 38,39 The present results showed that the expression of PErelated gene PLGF was inhibited under HG condition. This result indicates that hyperglycemia induced PE and reduced PLGF expression.…”

Section: Discussionsupporting

confidence: 50%

High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

Tao

Xia

Chen

et al. 2020

J of Obstet and Gynaecol

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Aim This study aimed to investigate the effect of high glucose (HG) level on the proliferation, migration and invasion of trophoblasts and determine the role of placental growth factor (PLGF) in the process. Methods HTR8‐S/Vneo was treated with different concentrations of d‐glucose (0, 10, 15, 20, 25 and 30 μM) at different times (0, 6, 12 and 24 h). qRT‐PCR and Western blot analyses were used to measure PLGF expression. The protein level of PLGF was measured by immunofluorescence. Cell proliferation was assessed with CCK‐8 analysis. Wound healing and transwell assays were used to evaluate cell migration and invasion. Intercellular ROS was detected with DCFH‐DA. Results After d‐glucose treatment, the viability decreased in 25 and 30 μM groups. The HG group (25 μM) showed inhibited cell migration and invasion ability. The mRNA and protein levels of PLGF decreased under HG condition. Elevated ROS production was also detected in the HG group. Knocked‐down PLGF expression enhanced increased ROS production and decreased cell migration and invasion, which reverted to the original levels after PLGF was overexpressed. Conclusion High glucose treatment inhibited HTR8‐S/Vneo viability, migration and invasion by downregulating PLGF expression.

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Section: Discussionsupporting

confidence: 50%

High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

Tao

Xia

Chen

et al. 2020

J of Obstet and Gynaecol

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“…Exendin‐4 has been shown to be capable of inhibiting the proliferation of human mesangial cells and downregulating the high‐glucose‐induced expression of TGF‐β1 and CTGF. Recently, our team reported that exendin‐4 significantly reduced Ang II and TGF‐β1 production through inhibition of ROS formation, but not ERK phosphorylation. These inhibitory effects of exendin‐4 were related mainly to the activation of the cyclic adenosine monophosphate–protein kinase A signaling pathway (Figure ).…”

Section: Other Possible Strategies For Prevention Of Islet Fibrosismentioning

confidence: 96%

“…Recently, our team reported that exendin-4 significantly reduced Ang II and TGF-b1 production through inhibition of ROS formation, but not ERK phosphorylation 73 . These inhibitory effects of exendin-4 were related mainly to the activation of the cyclic adenosine monophosphate-protein kinase A signaling pathway ( Figure 2).…”

Section: Other Possible Strategies For Prevention Of Islet Fibrosismentioning

confidence: 99%

Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

Yang

Kim

Park

et al. 2020

J of Diabetes Invest

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There are numerous lines of clinical evidence that inhibition of the renin–angiotensin system (RAS) can prevent and delay the development of diabetes. Also, the role of RAS in the pathogenesis of diabetes, including insulin resistance and β‐cell dysfunction, has been extensively investigated. Nevertheless, this role had not yet been fully shown. A variety of possible protective mechanisms for RAS blockers in the regulation of glucose homeostasis have been suggested. However, the direct effect on pancreatic islet fibrosis has only recently been spotlighted. Various degrees of islet fibrosis are often observed in the islets of patients with type 2 diabetes mellitus, which can be associated with a decrease in β‐cell mass and function in these patients. Pancreatic stellate cells are thought to be deeply involved in this islet fibrosis. In this process, the activation of RAS in islets is shown to transform quiescent pancreatic stellate cells into the activated form, stimulates their proliferation and consequently leads to islet fibrotic destruction. In this article, we introduce existing clinical and experimental evidence for diabetes prevention through inhibition of RAS, and review the responsible local RAS signaling pathways in pancreatic stellate cells. Finally, we propose possible targets for the prevention of islet fibrosis.

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“…In contrast, insufficient silicon intake is associated with a high risk of cardiovascular events and increases the case fatality rate [84]. Selenium often acts as a redox scavenger in the human body [27], an action which is essential to the restoration of impaired islets and vascular tissues in diabetes [85,86]. The liver is one of the organs with the highest selenium concentration [87].…”

Section: Elementsmentioning

confidence: 99%

Trace Elements, PPARs, and Metabolic Syndrome

Shi

Zou

Shen

et al. 2020

IJMS

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Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of Ppar-α; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of Ppar-γ, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.

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Suppression of ROS Production by Exendin-4 in PSC Attenuates the High Glucose-Induced Islet Fibrosis

Cited by 22 publications

References 28 publications

High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

High glucose condition inhibits trophoblast proliferation, migration and invasion by downregulating placental growth factor expression

Pancreatic stellate cells in the islets as a novel target to preserve the pancreatic β‐cell mass and function

Trace Elements, PPARs, and Metabolic Syndrome

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