Chikusetsu saponin IVa protects pancreatic β cell against intermittent high glucose-induced injury by activating Wnt/β-catenin/TCF7L2 pathway

Human GKβ (pancreatic β-cell glucokinase) is the main glucose-phosphorylating enzyme in pancreatic β-cells. It shares several structural, catalytic and regulatory properties with Hxk2 (hexokinase 2) from Saccharomyces cerevisiae. In fact, it has been previously described that expression of GKβ in yeast could replace Hxk2 in the glucose signalling pathway of S. cerevisiae. In the present study we report that GKβ exerts its regulatory role by association with the yeast transcriptional repressor Mig1 (multicopy inhibitor of GAL gene expression 1); the presence of Mig1 allows GKβ to bind to the SUC2 (sucrose fermentation 2) promoter, helping in this way in the maintenance of the repression of the SUC2 gene under high-glucose conditions. Since a similar mechanism has been described for the yeast Hxk2, the findings of the present study suggest that the function of the regulatory domain present in these two proteins has been conserved throughout evolution. In addition, we report that GKβ is enriched in the yeast nucleus of high-glucose growing cells, whereas it shows a mitochondrial localization upon removal of the sugar. However, GKβ does not exit the nucleus in the absence of Mig1, suggesting that Mig1 regulates the nuclear exit of GKβ under low-glucose conditions. We also report that binding of GKβ to Mig1 allows the latter protein to be located at the mitochondrial network under low-glucose conditions.

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Estrogen attenuates AGTR1 expression to reduce pancreatic β-cell death from high glucose

Scientific Reports ◽

10.1038/s41598-017-15237-4 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 2

Author(s):

Suwattanee Kooptiwut ◽

Keerati Wanchai ◽

Namoiy Semprasert ◽

Chatchawan Srisawat ◽

Pa-thai Yenchitsomanus

Keyword(s):

Cell Death ◽

High Glucose ◽

Pancreatic Β Cell ◽

Β Cell

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Real-time detection of single-living pancreatic β-cell by laser tweezers Raman spectroscopy: High glucose stimulation

Biopolymers ◽

10.1002/bip.21389 ◽

2010 ◽

Vol 93 (7) ◽

pp. 587-594 ◽

Cited By ~ 9

Author(s):

Xi Rong ◽

Shu-Shi Huang ◽

Xiao-Cong Kuang ◽

Hong Liu

Keyword(s):

Raman Spectroscopy ◽

Real Time ◽

High Glucose ◽

Laser Tweezers ◽

Pancreatic Β Cell ◽

Β Cell ◽

Glucose Stimulation ◽

Real Time Detection ◽

Single Living

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Cyanidin-3-rutinoside protects INS-1 pancreatic β cells against high glucose-induced glucotoxicity by apoptosis

Zeitschrift für Naturforschung C ◽

10.1515/znc-2017-0172 ◽

2018 ◽

Vol 73 (7-8) ◽

pp. 281-289 ◽

Cited By ~ 1

Author(s):

Kung-Ha Choi ◽

Mi Hwa Park ◽

Hyun Ah Lee ◽

Ji-Sook Han

Keyword(s):

Cell Death ◽

High Glucose ◽

Cell Damage ◽

Therapeutic Effects ◽

Dependent Manner ◽

Pancreatic Β Cell ◽

Β Cells ◽

Β Cell ◽

Pancreatic Β Cells ◽

Induced Apoptosis

Abstract Exposure to high levels of glucose may cause glucotoxicity, leading to pancreatic β cell dysfunction, including cell apoptosis and impaired glucose-stimulated insulin secretion. The aim of this study was to explore the effect of cyanidin-3-rutinoside (C3R), a derivative of anthocyanin, on glucotoxicity-induced apoptosis in INS-1 pancreatic β cells. Glucose (30 mM) treatment induced INS-1 pancreatic β cell death, but glucotoxicity and apoptosis significantly decreased in cells treated with 50 μM C3R compared to that observed in 30 mM glucose-treated cells. Furthermore, hyperglycemia increased intracellular reactive oxygen species (ROS), lipid peroxidation, and nitric oxide (NO) levels, while C3R treatment reduced these in a dose-dependent manner. C3R also increased the activity of antioxidant enzymes, markedly reduced the expression of pro-apoptotic proteins (such as Bax, cytochrome c, caspase 9 and caspase 3), and increased the expression of the anti-apoptotic protein, Bcl-2, in hyperglycemia-exposed cells. Finally, cell death was examined using annexin V/propidium iodide staining, which revealed that C3R significantly reduced high glucose-induced apoptosis. In conclusion, C3R may have therapeutic effects against hyperglycemia-induced β cell damage in diabetes.

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Testosterone reduces AGTR1 expression to prevent β-cell and islet apoptosis from glucotoxicity

Journal of Endocrinology ◽

10.1530/joe-14-0397 ◽

2014 ◽

Vol 224 (3) ◽

pp. 215-224 ◽

Cited By ~ 12

Author(s):

Suwattanee Kooptiwut ◽

Wanthanee Hanchang ◽

Namoiy Semprasert ◽

Mutita Junking ◽

Thawornchai Limjindaporn ◽

...

Keyword(s):

Oxidative Stress ◽

High Glucose ◽

Cell Apoptosis ◽

Caspase 3 ◽

Ang Ii ◽

Pancreatic Β Cell ◽

Glucose Medium ◽

Β Cell ◽

High Glucose Medium ◽

Cells Cultured

Hypogonadism in men is associated with an increased incidence of type 2 diabetes. Supplementation with testosterone has been shown to protect pancreatic β-cell against apoptosis due to toxic substances including streptozotocin and high glucose. One of the pathological mechanisms of glucose-induced pancreatic β-cell apoptosis is the induction of the local rennin–angiotensin–aldosterone system (RAAS). The role of testosterone in regulation of the pancreatic RAAS is still unknown. This study aims to investigate the protective action of testosterone against glucotoxicity-induced pancreatic β-cell apoptosis via alteration of the pancreatic RAAS pathway. Rat insulinoma cell line (INS-1) cells or isolated male mouse islets were cultured in basal and high-glucose media in the presence or absence of testosterone, losartan, and angiotensin II (Ang II), then cell apoptosis, cleaved caspase 3 expression, oxidative stress, and expression of angiotensin II type 1 receptor (AGTR1) and p47phox mRNA and protein were measured. Testosterone and losartan showed similar effects in reducing pancreatic β-cell apoptosis. Testosterone significantly reduced expression of AGTR1 protein in INS-1 cells cultured in high-glucose medium or high-glucose medium with Ang II. Testosterone decreased the expression of AGTR1 and p47phox mRNA and protein in comparison with levels in cells cultured in high-glucose medium alone. Furthermore, testosterone attenuated superoxide production when co-cultured with high-glucose medium. In contrast, when cultured in basal glucose, supplementation of testosterone did not have any effect on cell apoptosis, oxidative stress, and expression of AGT1R and p47phox. In addition, high-glucose medium did not increase cleaved caspase 3 in AGTR1 knockdown experiments. Thus, our results indicated that testosterone prevents pancreatic β-cell apoptosis due to glucotoxicity through reduction of the expression of ATGR1 and its signaling pathway.

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