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

2014 ◽  
Vol 224 (3) ◽  
pp. 215-224 ◽  
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.

scholarly journals CD36 regulates β cell differentiation and influences type 2 diabetic sepsis

2021 ◽  
Author(s):  
Huogen Liu ◽  
Ling Gu ◽  
Yundi Shi ◽  
Hailin Shu ◽  
Fengming Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Cell Clone ◽  
Quantitative Polymerase Chain Reaction ◽  
Control Group ◽  
Β Cell ◽  
Type 2 Diabetic

Abstract Background This study aimed to investigate the diagnostic function of CD36 in type 2 diabetic (T2DM) sepsis complications (T2DSC) and its effect on β-cell differentiation. Methods First, Age - and sex-matched T2DM patients, T2DSC patients and healthy people (50 cases each) were included. Quantitative polymerase chain reaction was used to measure CD36, FOXO1, PDX1, MAFA, insulin, SOX9, Neurog3 and NANOG expression in blood samples. Second, cultured human β-cell line EndoC-βH1 and the interference and overexpression of CD36. Cell clone, apoptosis, inflammatory cytokine, oxidative stress and β-cell differentiation related proteins were also analysed. Third, examined the role of CD36 in high glucose, LPS-induced β-cell. Results CD36 mRNA, and endocrine progenitor β-cell biomarkers SOX9, Neurog3 and NANOG were significantly increased in T2DM than control group, whereas the β-cell maturation biomarkers FOXO1, PDX1, MAFA and insulin were significantly decreased. Compared with the T2DM group, CD36 and FOXO1 were significantly increased in T2DSC, but PDX1, insulin, MAFA, SOX9, Neurog3 and NANOG were significantly decreased. The receiver operating characteristic curve revealed that CD36 was useful for distinguishing T2MD and T2DSC from the control group. Furthermore, CD36 overexpression increased β-cell apoptosis and the secretion of IL-1β, IL-8 TNF-α, malondialdehyde and reactive oxygen species. CD36 induced cell defferentiation. Lastly, CD36 knockdown could inhibit the high glucose and LPS-induced cell apoptosis, inflammatory, oxidative stress and cell defferentiation. Conclusion Significant increase in CD36 can be used as a biomarker for T2MD and T2DSC. CD36 promotes T2MD or T2DSC development by inducing β-cell inflammatory and oxidative stress and defferentiation.

Effect of Jinmaitong (筋脉通) serum on the proliferation of rat Schwann cells cultured in high glucose medium

2008 ◽  
Vol 14 (4) ◽  
pp. 293-297 ◽  
Author(s):  
Ling Qu ◽  
Xiao-chun Liang ◽  
Hong Zhang ◽  
Qun-li Wu ◽  
Lian-qing Sun ◽  
...  
Keyword(s):  
Schwann Cells ◽  
High Glucose ◽  
Glucose Medium ◽  
High Glucose Medium ◽  
Cells Cultured

scholarly journals Superoxide Destabilization of β-Catenin Augments Apoptosis of High-Glucose-Stressed Mesangial Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2934-2942 ◽  
Author(s):  
Chun-Liang Lin ◽  
Jeng-Yi Wang ◽  
Jih-Yang Ko ◽  
Kameswaran Surendran ◽  
Yu-Ting Huang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Renal Tissue ◽  
Dominant Negative ◽  
Gsk 3Β

Intense mesangial cell apoptosis contributes to the pathogenesis of diabetic nephropathy. Although reactive oxygen radicals and Wnt signaling components are potent regulators that modulate renal tissue remodeling and morphogenesis, cross-talk between oxidative stress and Wnt/β-catenin signaling in controlling high-glucose-impaired mesangial cell survival and renal function have not been tested. In this study, high glucose induced Ras and Rac1 activation, superoxide burst, and Wnt5a/β-catenin destabilization and subsequently promoted caspase-3 and poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures. The pharmacological and genetic suppression of superoxide synthesis by superoxide dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant-negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK-3β) activation and caspase-3 and poly (ADP-ribose) polymerase degradation. Inactivation of Ras and Racl also reversed Wnt/β-catenin expression and survival of mesangial cells. Stabilization of β-catenin by the transfection of stable β-catenin (Δ45) and kinase-inactive GSK-3β attenuated high-glucose-mediated mesangial cell apoptosis. Exogenous superoxide dismutase administration attenuated urinary protein secretion in diabetic rats and abrogated diabetes-mediated reactive oxygen radical synthesis in renal glomeruli. Immunohistological observation revealed that superoxide dismutase treatment abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) and increased Wnt5a/β-catenin expression in renal glomeruli. Taken together, high glucose induced oxidative stress and apoptosis in mesangial cells. The Ras and Rac1 regulation of superoxide appeared to raise apoptotic activity by activating GSK-3β and inhibiting Wnt5a/β-catenin signaling. Controlling oxidative stress and Wnt/β-catenin signaling has potential for protecting renal tissue against the deleterious effect of high glucose.

scholarly journals High glucose inhibits glucose‐6‐phosphate dehydrogenase, leading to increased oxidative stress and β‐cell apoptosis

2009 ◽  
Vol 24 (5) ◽  
pp. 1497-1505 ◽  
Author(s):  
Zhaoyun Zhang ◽  
Chong Wee Liew ◽  
Diane E. Handy ◽  
Yingyi Zhang ◽  
Jane A. Leopold ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Cell Apoptosis ◽  
Β Cell ◽  
Glucose 6 Phosphate Dehydrogenase

scholarly journals Cholesterol induces pancreatic β cell apoptosis through oxidative stress pathway

2011 ◽  
Vol 16 (5) ◽  
pp. 539-548 ◽  
Author(s):  
Xiuli Lu ◽  
Jianli Liu ◽  
Fangfang Hou ◽  
Zhenqing Liu ◽  
Xiangyu Cao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Oxidative Stress Pathway ◽  
Stress Pathway

scholarly journals Testosterone Protects Against Glucotoxicity-Induced Apoptosis of Pancreatic β-Cells (INS-1) and Male Mouse Pancreatic Islets

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4058-4067 ◽  
Author(s):  
Wanthanee Hanchang ◽  
Namoiy Semprasert ◽  
Thawornchai Limjindaporn ◽  
Pa-thai Yenchitsomanus ◽  
Suwattanee Kooptiwut
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
High Glucose ◽  
Male Mouse ◽  
Glucose Medium ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Stress Markers ◽  
High Glucose Medium ◽  
Cells Cultured

Male hypogonadism associates with type 2 diabetes, and T can protect pancreatic β-cells from glucotoxicity. However, the protective mechanism is still unclear. This study thus aims to examine the antiapoptotic mechanism of T in pancreatic β cells cultured in high-glucose medium. T (0.0005–2 μg/mL) was added to INS-1 cells cultured in basal glucose or high-glucose media. Then cellular apoptosis, oxidative stress, and cell viability were measured. Endoplasmic reticulum (ER) stress markers and sensors and the antiapoptotic protein (B-cell lymphoma 2) were investigated by real-time PCR and Western blot analysis. ER stress markers were also measured in male mouse pancreatic islet cultured in similar conditions. T (0.05 and 0.5 μg/mL) did not have any effect on apoptosis and viability of INS-1 cells cultured in basal glucose medium, but it could reduce apoptosis and increase viability of INS-1 cells cultured in high-glucose medium. The protective effect of T is diminished by androgen receptor inhibitor. T (0.05 μg/mL) could significantly reduce nitrotyrosine levels, mRNA, and protein levels of the ER stress markers and sensor those that were induced when INS-1 cells were cultured in high-glucose medium. It could also significantly increase the survival proteins, sarco/endoplasmic reticulum Ca2+ ATPase-2, and B-cell lymphoma 2 in INS-1 cells cultured in the same conditions. Similarly, it could reduce ER stress markers and increase sarco/endoplasmic reticulum Ca2+ ATPase protein levels in male mouse pancreatic islets cultured in high-glucose medium. T can protect against male pancreatic β-cell apoptosis from glucotoxicity via the reduction of both oxidative stress and ER stress.

scholarly journals Glucose and Prednisolone Alter Basic Fibroblast Growth Factor Expression in Peritoneal Mesothelial Cells and Fibroblasts

2001 ◽  
Vol 12 (12) ◽  
pp. 2787-2796
Author(s):  
Satoshi Ogata ◽  
Noriaki Yorioka ◽  
Nobuoki Kohno
Keyword(s):  
Growth Factor ◽  
High Glucose ◽  
Neutralizing Antibody ◽  
Mesothelial Cells ◽  
Fibroblast Growth ◽  
Glucose Medium ◽  
Peritoneal Fibrosis ◽  
Peritoneal Mesothelial Cells ◽  
High Glucose Medium ◽  
Cells Cultured

ABSTRACT. The mechanism of peritoneal fibrosis in patients on continuous ambulatory peritoneal dialysis is poorly understood. The production of basic fibroblast growth factor (bFGF) by human peritoneal mesothelial cells cultured in high glucose medium was investigated, and the behavior of peritoneal fibroblasts, as well as the inhibitory effect of prednisolone, was assessed. Reverse transcriptase-PCR and immunocytochemistry showed the expression of glucocorticoid receptors in mesothelial cells. The semiquantitative reverse transcriptase-PCR showed that high glucose medium (4.0%) increased bFGF mRNA by 2.5-fold relative to control medium (0.1% glucose), with 83% suppression of the increase by 1 μM prednisolone. The bFGF protein level in culture supernatant was also increased by 1.5-fold in high glucose medium, with this change showing 45% suppression by 1 μM prednisolone. These effects of prednisolone were prevented by a glucocorticoid receptor antagonist (RU486) in a concentration-dependent manner. The proliferation of peritoneal fibroblasts was increased 1.9-fold by the supernatant of mesothelial cells cultured in high glucose medium, with 85% suppression by 1 μM prednisolone and suppression to 16% below basal proliferation by an anti-bFGF neutralizing antibody (10 μg/ml), whereas proliferation showed a concentration-dependent increase on addition of an anti-transforming growth factor beta-neutralizing antibody. Recombinant bFGF (50 to 1000 pg/ml) likewise caused a concentration-dependent increase of peritoneal fibroblast proliferation and fibronectin release by these cells was also increased (at 50 to 5000 pg/ml). These results suggest the potential importance of bFGF for initiation of peritoneal fibrosis and the possible efficacy of glucocorticoids for preventing such fibrosis in patients receiving peritoneal dialysis.

Sign in / Sign up

Export Citation Format

Share Document