High glucose levels increase the expression of neurotrophic factors associated with p-p42/p44 MAPK in Schwann cells in vitro

Diabetes mellitus, a metabolic disease characterized by hyperglycemia and poor glucose control, is a risk factor for Mycobacterium tuberculosis (M. tuberculosis) infection and the development of active tuberculosis. To evaluate whether M. tuberculosis infection susceptibility is associated with an intrinsic factor in monocytes from type 2 diabetes (T2D) patients or it is associated with hyperglycemia per se, we analyzed TLR-2 and TLR-4 expression by flow cytometry and the cytokines IL-1β, IL-6, IL-8, IL-10, and TNF-α by cytometric bead array assays, either stimulated with TLR-2 and TLR-4 ligands or infected with M. tuberculosis in the whole blood from T2D patients (n=43) and healthy subjects (n=26) or in CD14+ monocytes from healthy subjects cultured in high glucose (HG) (30 mM). The intracellular growth of M. tuberculosis was evaluated by CFU counts at 0, 1, and 3 days in both monocytes from T2D patients and monocytes from healthy subjects cultured in HG. We did not find significant differences in TLR expression, cytokine production, or growth of M. tuberculosis in monocytes from T2D patients compared with those in monocytes from healthy subjects. Despite these results, in vitro assays of monocytes cultured with 30 mM glucose led to significantly increased TLR-2 and TLR-4 basal expression compared to those of monocytes cultured with 11 mM glucose (P<0.05). Conversely, the production of IL-6 by TLR-2 ligand stimulation, of IL-1β, IL-6, and IL-8 by TLR-4 ligand stimulation, and of IL-8 by M. tuberculosis infection significantly decreased in monocytes cultured in HG (P<0.05). Additionally, the intracellular survival of M. tuberculosis increased in monocytes in HG after day 3 of culture (P<0.05). In conclusion, HG decreased IL-8 production and the intracellular growth control of M. tuberculosis by monocytes, supporting the hypothesis that hyperglycemia plays an important role in the impaired immune responses to M. tuberculosis in patients with T2D.

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Elevated glucose acts directly on osteocytes to increase sclerostin expression in diabetes

Scientific Reports ◽

10.1038/s41598-019-52224-3 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 6

Author(s):

Donna M. Pacicca ◽

Tammy Brown ◽

Dara Watkins ◽

Karen Kover ◽

Yun Yan ◽

...

Keyword(s):

Bone Quality ◽

High Glucose ◽

Negative Impact ◽

Negative Regulator ◽

Diabetic Rat ◽

Diabetic Patients ◽

Bone Homeostasis ◽

Glucose Levels ◽

Elevated Glucose

AbstractBone quality in diabetic patients is compromised, leading to weaker bones and increased fracture risk. However, the mechanism by which this occurs in diabetic bone remains to be fully elucidated. We hypothesized that elevated glucose and glucose variation would affect the function of osteocytes, essential regulators of bone homeostasis and quality. To first test this hypothesis, we used the IDG-SW3 osteocyte-like cell line to examine the effects of glucose levels on osteocyte function and viability in vitro. We confirmed our in vitro findings using the in vivo streptozotocin-induced (STZ) diabetic rat model and ex-vivo cultured osteocytes from these rats. IDG-SW3 cells cultured under high glucose conditions displayed significantly increased Sost mRNA(100-fold) and sclerostin protein, a negative regulator of bone formation(5000-fold), compared to cells in control media. mRNA expression of osteoblast markers such as Osx, Ocn and Col1a1 was unaffected by glucose. Factors associated with osteoclast activation were affected by glucose, with Rankl being upregulated by low glucose. Opg was also transiently upregulated by high glucose in mature IDG-SW3 cells. Induction of diabetes in Sprague-Dawley rats via a single dose of STZ (70 mg/kg) resulted in elevated maximum glucose and increased variability compared to control animals (670/796 vs. 102/142 mg/dL). This was accompanied by increased Sost/sclerostin expression in the osteocytes of these animals. These results show that glucose levels directly regulate osteocyte function through sclerostin expression and suggest a potential mechanism for the negative impact of diabetes on bone quality.

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PHOSPHATIDYLINOSITOL -3KINASE (PI3K) DI PERBENIHAN ADIPOSIT YANG DIPAJAN GLUKOSA TINGGI DENGAN RETINOL

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v22i2.1111 ◽

2018 ◽

Vol 22 (2) ◽

pp. 109

Author(s):

Novi Khila Firani ◽

Bambang Prijadi

Keyword(s):

High Glucose ◽

Glucose Transporter ◽

Determination Method ◽

Glucose Transporter 4 ◽

Phosphatidylinositol 3 Kinase ◽

Elisa Method ◽

Glucose Levels ◽

Glucose Exposure ◽

The Mean

Retinol is one of the active forms of vitamin A. In the previous study, it was known that retinol level in serum of DM patient waslower than in healthy people, which correlated with an increase of the glucose levels in these patients. The importance of retinol in insulinsignaling mechanisms that play a role in the pathogenesis of DM is still unknown. One of the components that play a role in insulinsignaling on adipocytes is phosphatidylinositol-3 kinase (PI3K), which encourages the translocation of glucose transporter-4 (GLUT4) tothe cell surface. The aim of this study was to know the importance of retinol therapy in the levels of PI3K enzyme on visceral adipocyteculture with high glucose exposure (25 mM) as a model of DM in vitro by determination method. Retinol therapy was given at a doseof 0.1 μM, 1 μM , and 10 μM. Measurement of PI3K level was done by ELISA method. The mean (SD) levels of PI3K enzyme were 1.91(0.27), 0.94 (0.15), 1.98 (0.22), 1.69 (0.81), 2.04 (0.16) ng/mL respectively, for adipocyte cultures exposed to 5mM glucose (as aphysiological condition), 25mM glucose, and 25mM glucose concentration with doses of retinol therapy 0.1 μM, 1 μM and10 μM. Theresults of this study indicated that high glucose exposure (25 mM) decreased the level of PI3K compared with adipocyte’s culture on5 mM glucose exposure. Retinol therapy with a dose of 0.1μM, 1μM and10 μM on adipocyte culture exposed with high glucose couldincrease the levels of PI3K.

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SENP3 regulates high glucose-induced endothelial dysfunction via ROS dependent signaling

Diabetes and Vascular Disease Research ◽

10.1177/1479164120970895 ◽

2020 ◽

Vol 17 (6) ◽

pp. 147916412097089

Author(s):

Fuheng Chen ◽

Dongdong Ma ◽

Aizhong Li

Keyword(s):

Endothelial Dysfunction ◽

High Glucose ◽

Type I Diabetes ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Type I ◽

Dependent Manner ◽

Glucose Levels ◽

And Migration

Background: The current study aimed to explore the role of SENP3 in endothelial cell dysfunction in a high-glucose setting. Methods: The gene and protein expressions of SENP3 in high-glucose cultured HAECs were examined using quantitative PCR and western blotting. The effects of SENP3 on HAEC viability, apoptosis, migration, and endothelial–monocyte adhesion were evaluated in vitro by knockdown. Moreover, a mouse streptozotocin-induced type I diabetes model was established for SENP3 expression assessment. In addition, the effects of SENP3 on ROS-related signaling pathways were investigated in high-glucose cultured HAECs. Results: Significantly increased levels of SENP3 mRNA and protein were found in high-glucose cultured HAECs in a time-dependent manner. SENP3 knockdown reversed high glucose-induced HAEC viability, apoptosis, and migration reduction. SENP3 knockdown attenuated the high glucose-induced intercellular adhesion of THP-1 monocytic cells and HAECs via downregulation of ICAM-1 and VCAM-1 expression. Increased levels of SENP3, ICAM-1, and VCAM-1 expression were observed in the aorta tissue of mice with type I diabetes. Downregulation of SENP3 expression was observed in HAECs cultured with high glucose levels using the free radical scavenger N-acetyl-L-cysteine or NOX4 siRNA. Conclusions: SENP3 was involved in high glucose-induced endothelial dysfunction, and ROS-dependent signaling served as the mechanism.

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Protective effect of hydrogen-rich medium against high glucose-induced apoptosis of Schwann cells in vitro

Molecular Medicine Reports ◽

10.3892/mmr.2015.3874 ◽

2015 ◽

Vol 12 (3) ◽

pp. 3986-3992 ◽

Cited By ~ 13

Author(s):

YANG YU ◽

XIAOYE MA ◽

TAO YANG ◽

BO LI ◽

KELIANG XIE ◽

...

Keyword(s):

Protective Effect ◽

Schwann Cells ◽

High Glucose ◽

Rich Medium ◽

Induced Apoptosis

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Decrease of Klotho in the Kidney of Streptozotocin-Induced Diabetic Rats

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/513853 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 31

Author(s):

Meng-Fu Cheng ◽

Li-Jen Chen ◽

Juei-Tang Cheng

Keyword(s):

Oxidative Stress ◽

High Glucose ◽

Diabetic Rats ◽

Glucose Levels ◽

Renal Functions ◽

Blood Glucose Levels ◽

Convoluted Tubules ◽

The Brain ◽

Darby Canine Kidney

Theklothogene is expressed in a limited number of tissues, most notably in distal convoluted tubules in the kidney and choroid plexus in the brain. A previous study suggested that Klotho increases resistance to oxidative stress. However, changes of Klotho expression in high glucose-induced oxidative stress remain unclear. In the present study, we used streptozotocin-induced diabetic rats (STZ rats) to examine the effects of insulin, phloridzin or antioxidant, tiron on diabetic nephropathy. Both insulin and phloridzin reversed the lower Klotho expression levels in kidneys of STZ rats by the correction of hyperglycemia. Also, renal functions were improved by these treatments. In addition to the improvement of renal functions, the decrease of Klotho expression in kidney of STZ rats was also reversed by tiron without changing blood glucose levels. The reduction of oxidative stress induced by high glucose can be considered for this action of tiron. This view was further confirmed in vitro using high glucose-exposed Madin-Darby canine kidney (MDCK) epithelial cells. Thus, we suggest that decrease of oxidative stress is not only responsible for the improvement of renal function but also for the recovery of Klotho expression in kidney of STZ rats.

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Hyperglycemia exacerbates cadmium-induced glomerular nephrosis

Toxicology and Industrial Health ◽

10.1177/07482337211037880 ◽

2021 ◽

pp. 074823372110378

Author(s):

Mengyang Li ◽

Xiuxiu Liu ◽

Zengli Zhang

Keyword(s):

High Glucose ◽

Saline Control ◽

In Vivo Models ◽

Nitrogen Levels ◽

Glucose Levels ◽

Elevated Glucose ◽

Low Glucose ◽

Cd Exposure

Current research suggests that cadmium (Cd) exposure may be associated with the progression of diabetic nephropathy; however, the details of this relationship are insufficiently understood. The present study investigated the effects of elevated glucose on Cd-induced toxicity to glomerular cells using in vitro and in vivo models, and it demonstrated that Cd exposure and the hyperglycemia of diabetes acting together increased the risk of developing glomerular nephrosis . In vitro, human podocytes were exposed to a DMEM low-glucose media without (control), or with Cd (as CdCl2), or a high-glucose media plus Cd. The CCK-8, ROS, apoptosis, and mitochondrial transmembrane potential (ΔΨm) assays showed that human podocytes exposed to Cd in a high-glucose media had greater degrees of injury compared with cells treated with Cd at low (euglycemic)-glucose levels. In vivo, diabetic hyperglycemia was induced by streptozotocin in 8-week-old male C57BL/6 mice to which either CdCl2 or saline (control) was intraperitoneally injected twice weekly for 24 weeks. Compared with euglycemic saline-treated controls, the diabetic mice exposed to Cd demonstrated decreased body weight and increased blood urea nitrogen levels along with histopathological renal architecture changes including collagen fiber accumulation. The results of this study supported the hypothesis that hyperglycemia plus Cd exposure increases the risk of damage to glomerular podocytes compared with Cd exposure in euglycemia.

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In Vitro Increase in Intracellular Calcium Concentrations Induced by Low or High Extracellular Glucose Levels in Ependymocytes and Serotonergic Neurons of the Rat Lower Brainstem

Endocrinology ◽

10.1210/en.2003-1191 ◽

2004 ◽

Vol 145 (5) ◽

pp. 2507-2515 ◽

Cited By ~ 34

Author(s):

Ryutaro Moriyama ◽

Hiroko Tsukamura ◽

Mika Kinoshita ◽

Hirokatsu Okazaki ◽

Yukio Kato ◽

...

Keyword(s):

Intracellular Calcium ◽

High Glucose ◽

Male Rats ◽

Dependent Manner ◽

Isolated Cells ◽

Serotonergic Neurons ◽

Glucose Levels ◽

Extracellular Glucose ◽

Low Glucose

Abstract Pancreatic glucokinase (GK)-like immunoreactivities are located in ependymocytes and serotonergic neurons of the rat brain. The present study investigated in vitro changes in intracellular calcium concentrations ([Ca2+]i) in response to low (2 mm) or high (20 mm) extracellular glucose concentrations in isolated cells from the wall of the central canal (CC), raphe obscurus nucleus (ROb), ventromedial hypothalamus (VMH), and lateral hypothalamic area (LHA) in male rats. An increase in [Ca2+]i was found in cells from the CC (21.1% or 9.8% of ependymocytes), ROb (10.9% or 14.5% of serotonergic neurons), VMH (7.8% and 25.2% of neurons), and LHA (20% or 15.7% of neurons), when extracellular glucose levels were changed from 10 to either 2 or 20 mm, respectively. Most of the ependymocytes and serotonergic neurons responding to the glucose changes were immunoreactive to the anti-GK in the CC (96.8% for low glucose and 100% for high glucose) and ROb (100% for low and high glucose). The [Ca2+]i increase was blocked with calcium-free medium or L-type calcium channel blocker. Cells with an increase in [Ca2+]i in response to low glucose did not respond to high glucose and vice versa. Inhibition of GK activity with acute alloxan treatment blocked low or high glucose-induced [Ca2+]i increases in most GK-immunoreactive cells from the CC or ROb. The glucose-sensitive [Ca2+]i increase in neurons of the VMH and LHA was also alloxan-sensitive, but no cells taken from the VMH and LHA were immunoreactive to the antibody used. The present study further indicates that ependymocytes of the CC and serotonergic neurons in the ROb are also sensitive to the changes in extracellular glucose in a GK-dependent manner, but that the subtype of GK in these cells could be different from that in the VMH and LHA.

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Ginsenoside Rg1 Alleviates Podocyte EMT Passage by Regulating AKT/GSK3 β/β-Catenin Pathway by Restoring Autophagic Activity

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1903627 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Yimin Shi ◽

Yanbin Gao ◽

Tao Wang ◽

Xiaolei Wang ◽

Jiaxin He ◽

...

Keyword(s):

High Glucose ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Diabetic Rats ◽

Ginsenoside Rg1 ◽

Glomerular Diseases ◽

Mesenchymal Transition ◽

Glucose Levels ◽

Autophagic Activity

Background. Diabetic nephropathy (DN), a complication of diabetes, is the result of high glucose-induced pathological changes in podocytes, such as epithelial-mesenchymal transition (EMT). Autophagy is an important mechanism of podocyte repair. Ginsenoside Rg1, the active ingredient of ginseng extract, has antifibrotic and proautophagic effects. Therefore, we hypothesized that ginsenoside Rg1 can reverse podocyte EMT via autophagy and alleviate DN. Aim. This study aimed to investigate the effect of ginsenoside Rg1 on DN rats and high glucose-induced podocyte EMT by regulating the AKT/GSK3β/β-catenin pathway by restoring autophagy activity. Methods. Diabetic rats induced by STZ injection were treated with 50 mg/kg ginsenoside Rg1 for 8 weeks, and the renal functional, metabolic, and histopathological indices were evaluated. DN was simulated in vitro by exposing podocytes to high glucose levels and treated with ginsenoside Rg1. The expression of EMT and autophagy-related markers was analyzed in vivo and in vitro by immunofluorescence, western blotting, and real-time PCR. Results. Ginsenoside Rg1 significantly alleviated renal fibrosis and podocyte EMT in diabetic rats, and podocytes exposed to high glucose levels, which was abolished by the autophagy inhibitor 3-MA. Furthermore, ginsenoside Rg1 regulated the AKT/GSK3 β/β-catenin pathway by restoring autophagic activity. Conclusion. Ginsenoside Rg1 alleviated podocyte EMT by enhancing AKT/GSK3β/β-catenin pathway-mediated autophagy, indicating its therapeutic potential for DN and other glomerular diseases.

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