Methylglyoxal Impairs Insulin Secretion of Pancreatic<i>β</i>-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs

Bo, Jinshuang; Xie, Shiya; Guo, Yi; Zhang, Chunli; Guan, Yanfei; Li, Chunmei; Lü, Jianxin; Meng, Qing H.

doi:10.1155/2016/2029854

Cited by 41 publications

(37 citation statements)

References 37 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We detected apoptotic cells and apoptotic proteins, The results showed that IRI can effectively upregulate the production of the apoptotic protein caspase 3. Some studies have focused on the use of proprietary Chinese medicines for the antioxidation and anti-apoptosis relief of IRI, but the effects of these exogenous treatments are uneven and have a detrimental effect on other tissues (Bo et al, 2015;Hill et al, 2008;Lin et al, 2003). Thus, the activation of endogenous protection is still the focus of research.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice

Zhang¹,

Guo²,

Li³

et al. 2019

Molecular Membrane Biology

View full text Add to dashboard Cite

Background and objective: Renal ischaemia reperfusion injury (IRI), characterized by excessive cell apoptosis and inflammation, remains a clinical challenge. Mitochondrial membrane potential is related to apoptosis and inflammation of IRI. Previous studies have indicated that uncoupling protein 2 (UCP2) and its receptors play an important role in inflammation, apoptosis and injuries, especially in oxidative stress injury. However, the underlying mechanisms of UCP2 in IRI are still not fully understood. Methods and results: In the present study, male C57 mice were randomly divided into three groups:sham, IR, and UCP2-/-+IR. The IRI model was established by removing the right kidney and clamping the left kidney for 45 min followed by reperfusion. Blood urea nitrogen (BUN) and creatinine were higher in UCP2-/-+IR mouse serum than in IR mouse serum. In addition, relative to the IR group, UCP2-/-+IR mouse renal cells had increased reactive oxygen species (ROS) production, aggravating tissue damage. We examined changes in the NFjB pathway and found that after UCP2 knockdown, IjB and IKK phosphorylation increased, and nuclear NFjB increased, which stimulated inflammation. Moreover, there was an increase in apoptosis in the UCP2-/-+IR group. Conclusion: UCP2 can prevent IRI in C57 mice. Mechanistically, UCP2 may decrease ROS expression, NFjB activation and caspase-3 cleavage, rendering UCP2 a potential therapeutic target against IRI.

show abstract

Section: Discussionmentioning

confidence: 99%

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice

Zhang¹,

Guo²,

Li³

et al. 2019

Molecular Membrane Biology

View full text Add to dashboard Cite

show abstract

“…Analysis of MIN6 (mouse insulinoma cells) and INS1 (rat insulinoma cells) cells after 3 h of MG incubation with either 0.05 or 0.1 mM revealed decreased insulin secretion when stimulated with 5 mM or 25 mM glucose compared to control cells [61]. Furthermore, 0.1 mM, but not 0.05 mM of MG induced apoptosis in MIN6 cells.…”

Section: Effects On Murine Pancreatic β-Cellsmentioning

confidence: 97%

“…UCP2 facilitates proton leakage to reduce the MMP and thus to reduce ATP generation. Reduced ATP production ultimately results in β-cell dysfunction [61,62,64].…”

Section: Effects On Murine Pancreatic β-Cellsmentioning

confidence: 99%

Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Zemva

Pfaff

Groener

et al. 2018

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

Levels of reactive metabolites such as reactive carbonyl and oxygen species are increased in patients with diabetes mellitus. The most important reactive dicarbonyl species, methylglyoxal (MG), formed as by-product during glucose metabolism, is more and more recognized as a trigger for the development and progression of diabetic complications. Although it is clear that MG provokes toxic effects, it is currently not well understood what cellular changes MG induces on a molecular level that may lead to pathophysiological conditions found in long-term diabetic complications. Here we review the current knowledge about the molecular effects that MG can induce in a cell. Within the mammalian system, we will focus mostly on the metabolic effects MG exerts when applied systemically to rodents or when applied to pancreatic β-cells and adipocytes. Due to the common limitations associated with complex model organisms, we then summarize how yeast as a very simple model organism can help to gain valuable comprehensive information on general defence pathways cells exert in response to MG stress. Pioneering studies in additional rather simple eukaryotic model organisms suggest that many cellular reactions in response to MG are highly conserved throughout evolution.

show abstract

“…Excessive insulin cannot be utilized by the cells, which inhibit glucose uptake in adipose tissue and increase inflammatory cytokines (Qatanani and Lazar, 2007). Previous studies have shown that the plasma concentrations of advanced glycation end products (AGEs) and methylglyoxal (MG) are increased in obesity and in patients with insulin resistance (Bo et al, 2016). Furthermore, long-term intake of AGEs and MG could increase AGEs and MG levels in the body, and circulating of AGEs in the body is not easily eliminated (Sims et al, 2010;Tikellis et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Effect of Phyllanthus emblica L. fruit on improving regulation of methylglyoxal-induced insulin resistance in 3T3-L1 cells

Chen¹,

Tung²,

Chen³

et al. 2018

JFB

View full text Add to dashboard Cite

The increasing methylglyoxal (MG) level of body has been found in people with obesity and insulin resistance, resulting from their dietary style and abnormal metabolic functions. MG promotes inflammation, oxidative stress, glycation, and all of which are closely related to insulin resistance and chronic diseases. Phyllanthus emblica L. fruit has various bioactivities such as anti-inflammation, anti-diabetes, anti-nonalcoholic fatty liver, and anti-dyslipidemia. Therefore, this study was aimed to investigate the effects of water extract of P. emblica (WEPE) and its enriched compound, ellagic acid, on MG-induced inflammation, insulin resistance, and lipogenesis in 3T3-L1 cells. The results showed that MG activated the peroxisome proliferator activated receptor-gamma (PPARγ) and CCAAT/ enhancer-binding protein alpha (C/EBPα), which can increase adipogenesis in adipocytes. In addition, MG enhanced pro-inflammatory cytokine IL-6 protein expression and release through the activation of MAPK and NF-κB signaling pathway, as well as increasing the monocyte chemoattractant protein-1 expression to cause macrophage infiltration. MG also significantly reduced glucose uptake, indicating that insulin resistance in obese patients may be related to MG generation. WEPE and ellagic acid effectively decreased IL-6 protein expression and cytokine release through inactivation of JNK and p65 pathways. WEPE and ellagic acid significantly increased glucose uptake and reduced insulin resistance by MG treatment. WEPE also decreased the protein-tyrosine phosphatase 1B to reduce insulin resistance and inhibited MG-induced fat accumulation related proteins such as PPARγ, C/EBPα, FAS, and p-ACC. Therefore, WEPE may have the potential to ameliorate MG-induced inflammation, increase glucose uptake, and decrease fat accumulation.

show abstract

Methylglyoxal Impairs Insulin Secretion of Pancreaticβ-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs

Cited by 41 publications

References 37 publications

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice

Uncoupling protein 2 prevents ischaemia reperfusion injury through the regulation ROS/NF-κB signalling in mice

Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Effect of Phyllanthus emblica L. fruit on improving regulation of methylglyoxal-induced insulin resistance in 3T3-L1 cells

Contact Info

Product

Resources

About