scholarly journals Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose ConcentrationsIn Vitroand in Islets Transplanted to Diabetic NOD MiceIn Vivo

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Eva Ludvigsen ◽  
Mats Stridsberg ◽  
Eva T. Janson ◽  
Stellan Sandler
Keyword(s):  
Pancreatic Islets ◽  
High Glucose ◽  
Somatostatin Receptors ◽  
Nod Mice ◽  
Diabetic Mice ◽  
Altered Expression ◽  
High Glucose Condition ◽  
Cell Expression

Somatostatin acts via five receptors (sst1-5). We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentrationin vitroas compared to the islet transplantationin vivoto diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

scholarly journals Increased long noncoding RNA maternally expressed gene 3 contributes to podocyte injury induced by high glucose through regulation of mitochondrial fission

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Qiongxia Deng ◽  
Ruowei Wen ◽  
Sirui Liu ◽  
Xiaoqiu Chen ◽  
Shicong Song ◽  
...  
Keyword(s):  
High Glucose ◽  
Noncoding Rna ◽  
Diabetic Kidney Disease ◽  
Mitochondrial Fission ◽  
Diabetic Mice ◽  
Podocyte Injury ◽  
Mitochondrial Translocation ◽  
Maternally Expressed Gene 3

Abstract Excessive mitochondrial fission plays a key role in podocyte injury in diabetic kidney disease (DKD), and long noncoding RNAs (lncRNAs) are important in the development and progression of DKD. However, lncRNA regulation of mitochondrial fission in podocytes is poorly understood. Here, we studied lncRNA maternally expressed gene 3 (Meg3) in mitochondrial fission in vivo and in vitro using human podocytes and Meg3 podocyte-specific knockdown mice. Expression of lncRNA Meg3 in STZ-induced diabetic mice was higher, and correlated with the number of podocytes. Excessive mitochondrial fission of podocytes and renal histopathological and physiological parameters were improved in podocyte-specific Meg3 knockdown diabetic mice. Elongated mitochondria with attenuated podocyte damage, as well as mitochondrial translocation of dynamin-related protein 1 (Drp1), were decreased in Meg3 knockout podocytes. By contrast, increased fragmented mitochondria, podocyte injury, and Drp1 expression and phosphorylation were observed in lncRNA Meg3-overexpressing podocytes. Treatment with Mdivi1 significantly blunted more fragmented mitochondria and reduced podocyte injury in lncRNA Meg3-overexpressing podocytes. Finally, fragmented mitochondria and Drp1 mitochondrial translocation induced by high glucose were reduced following treatment with Mdivi1. Our data show that expression of Meg3 in podocytes in both human cells and diabetic mice was higher, which regulates mitochondrial fission and contributes to podocyte injury through increased Drp1 and its translocation to mitochondria.

Activation of mTOR signaling mediates the increased expression of AChE in high glucose condition: in vitro and in vivo evidences

2015 ◽  
Vol 53 (7) ◽  
pp. 4972-4980 ◽  
Author(s):  
Yao-Wu Liu ◽  
Liang Zhang ◽  
Yu Li ◽  
Ya-Qin Cheng ◽  
Xia Zhu ◽  
...  
Keyword(s):  
High Glucose ◽  
Mtor Signaling ◽  
High Glucose Condition ◽  
Glucose Condition

scholarly journals S-Nitrosylation of RhoGAP Myosin9A Is Altered in Advanced Diabetic Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Qi Li ◽  
Delma Veron ◽  
Alda Tufro
Keyword(s):  
Kidney Disease ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Diabetic Mice ◽  
Post Translational Modification ◽  
No Donor ◽  
Diabetic Kidney ◽  
Rhoa Activity

The molecular pathogenesis of diabetic kidney disease progression is complex and remains unresolved. Rho-GAP MYO9A was recently identified as a novel podocyte protein and a candidate gene for monogenic FSGS. Myo9A involvement in diabetic kidney disease has been suggested. Here, we examined the effect of diabetic milieu on Myo9A expression in vivo and in vitro. We determined that Myo9A undergoes S-nitrosylation, a post-translational modification dependent on nitric oxide (NO) availability. Diabetic mice with nodular glomerulosclerosis and severe proteinuria associated with doxycycline-induced, podocyte-specific VEGF164 gain-of-function showed markedly decreased glomerular Myo9A expression and S-nitrosylation, as compared to uninduced diabetic mice. Immortalized mouse podocytes exposed to high glucose revealed decreased Myo9A expression, assessed by qPCR, immunoblot and immunocytochemistry, and reduced Myo9A S-nitrosylation (SNO-Myo9A), assessed by proximity link assay and biotin switch test, functionally resulting in abnormal podocyte migration. These defects were abrogated by exposure to a NO donor and were not due to hyperosmolarity. Our data demonstrate that high-glucose induced decrease of both Myo9A expression and SNO-Myo9A is regulated by NO availability. We detected S-nitrosylation of Myo9A interacting proteins RhoA and actin, which was also altered by high glucose and NO dependent. RhoA activity inversely related to SNO-RhoA. Collectively, data suggest that dysregulation of SNO-Myo9A, SNO-RhoA and SNO-actin may contribute to the pathogenesis of advanced diabetic kidney disease and may be amenable to therapeutic targeting.

scholarly journals FSP-1 Impairs the Function of Endothelium Leading to Failure of Arteriovenous Grafts in Diabetic Mice

Endocrinology ◽  
2015 ◽  
Vol 156 (6) ◽  
pp. 2200-2210 ◽  
Author(s):  
Jinlong Luo ◽  
Ming Liang ◽  
William E. Mitch ◽  
Farhad R. Danesh ◽  
Michael Yu ◽  
...  
Keyword(s):  
High Glucose ◽  
Coiled Coil ◽  
Inflammatory Cells ◽  
Specific Protein ◽  
Neointima Formation ◽  
Diabetic Mice ◽  
Junction Molecules ◽  
Myosin Light Chain 2

Abstract To understand how endothelial cell (EC) dysfunction contributes to the failure of arteriovenous graft (AVG), we investigated the role of fibroblast-specific protein 1 (FSP-1) in cultured ECs and a mouse AVG model. In vitro, we uncovered a new FSP-1-dependent pathway that activates rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) in ECs, leading to phosphorylation of myosin light chain 2 resulting in EC dysfunction. In cultured ECs, high glucose stimulated FSP-1 expression and increased permeability of an EC monolayer. The increase in permeability by the high glucose concentration was mediated by FSP-1 expression. Treatment of cultured ECs with FSP-1 caused leakage of the endothelial barrier plus increased expression of adhesion molecules and decreased expression of junction molecules. These responses were initiated by binding of FSP-1 to receptor for advanced glycation end products, which resulted in ROCK1 activation. In vivo, diabetes increased infiltration of inflammatory cells into AVGs and stimulated neointima formation. Increased FSP-1 expression and ROCK1 activation were found in AVGs of diabetic mice. Blocking FSP-1 suppressed diabetes-induced ROCK1 activation in AVGs. In mice with FSP-1 knockout or with ROCK1 knockout, accumulation of inflammatory cells and neointima formation in AVG were attenuated despite diabetes. Thus, mechanisms of inhibiting FSP-1 in ECs could improve AVG function.

scholarly journals Inhibition of HDAC3 Ameliorates Cerebral Ischemia Reperfusion Injury in Diabetic Mice In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Bo Zhao ◽  
Quan Yuan ◽  
Jia-bao Hou ◽  
Zhong-yuan Xia ◽  
Li-ying Zhan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
High Glucose ◽  
Ischemia Reperfusion ◽  
Pathological Process ◽  
Diabetic Mice ◽  
Diabetic State ◽  
Cerebral Ischemia Reperfusion

Background. A substantial increase in histone deacetylase 3 (HDAC3) expression is implicated in the pathological process of diabetes and stroke. However, it is unclear whether HDAC3 plays an important role in diabetes complicated with stroke. We aimed to explore the role and the potential mechanisms of HDAC3 in cerebral ischemia/reperfusion (I/R) injury in diabetic state. Methods. Diabetic mice were subjected to 1 h ischemia, followed by 24 h reperfusion. PC12 cells were exposed to high glucose for 24 h, followed by 3 h of hypoxia and 6 h of reoxygenation (H/R). Diabetic mice received RGFP966 (the specific HDAC3 inhibitor) or vehicle 30 minutes before the middle cerebral artery occlusion (MCAO), and high glucose-incubated PC12 cells were pretreated with RGFP966 or vehicle 6 h before H/R. Results. HDAC3 inhibition reduced the cerebral infarct volume, ameliorated pathological changes, improved the cell viability and cytotoxicity, alleviated apoptosis, attenuated oxidative stress, and enhanced autophagy in cerebral I/R injury model in diabetic state in vivo and in vitro. Furthermore, we found that the expression of HDAC3 was remarkably amplified, and the Bmal1 expression was notably decreased in diabetic mice with cerebral I/R, whereas this phenomenon was obviously reversed by RGFP966 pretreatment. Conclusions. These results suggested that the HDAC3 was involved in the pathological process of the complex disease of diabetic stroke. Suppression of HDAC3 exerted protective effects against cerebral I/R injury in diabetic state in vivo and in vitro via the modulation of oxidative stress, apoptosis, and autophagy, which might be mediated by the upregulation of Bmal1.

Beneficial effect of flax seeds in streptozotocin (STZ) induced diabetic mice: isolation of active fraction having islet regenerative and glucosidase inhibitory properties

2013 ◽  
Vol 91 (5) ◽  
pp. 325-331 ◽  
Author(s):  
Menakshi Bhat Dusane ◽  
Bimba N. Joshi
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Islets ◽  
Immunohistochemical Analysis ◽  
Diabetic Mice ◽  
Active Fraction ◽  
Beneficial Effects ◽  
Endogenous Insulin ◽  
Flax Seeds

Diabetes mellitus is a metabolic disorder that affects millions of people worldwide. Present study highlights the antidiabetogenic property of Linum usitassimum active fraction (LU6) in streptozotocin (STZ) induced diabetic Swiss mice. Treatment with LU6 fraction showed improved glucose utilization with increase in liver glucose-6-phosphate dehydrogenase enzyme activity and normal glycogenesis in hepatic and muscle tissues. Reduction in pancreatic and intestinal glucosidase inhibitory activity was observed with LU6 treatment, indicating beneficial effects in reducing postprandial hyperglycemia (PPHG). Normalization of plasma insulin and C-peptide levels were observed in diabetic mice, indicating endogenous insulin secretion after the treatment with LU6. The histochemical and immunohistochemical analysis on pancreatic islets suggests the role of LU6 fraction in islet regeneration and insulin secretion as evident in increase functional pancreatic islets producing insulin. Furthermore, significant insulin producing islet formation was also observed in in vitro PANC-1 cells after LU6 treatment, indicating the cellular aggregates to be newly formed islets. This suggests the potential of LU6 fraction in the formation of new islets in vitro, as well as in vivo. Thus, LU6 can be used as a neutraceutical-based first-line treatment for diabetes.

scholarly journals Ammonium Glycyrrhizinate Prevents Apoptosis and Mitochondrial Dysfunction Induced by High Glucose in SH-SY5Y Cell Line and Counteracts Neuropathic Pain in Streptozotocin-Induced Diabetic Mice

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 608
Author(s):  
Laura Ciarlo ◽  
Francesca Marzoli ◽  
Paola Minosi ◽  
Paola Matarrese ◽  
Stefano Pieretti
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
High Glucose ◽  
Diabetic Peripheral Neuropathy ◽  
Glycyrrhizic Acid ◽  
Repeated Treatment ◽  
Diabetic Mice ◽  
Painful Condition

Glycyrrhiza glabra, commonly known as liquorice, contains several bioactive compounds such as flavonoids, sterols, triterpene, and saponins; among which, glycyrrhizic acid, an oleanane-type saponin, is the most abundant component in liquorice root. Diabetic peripheral neuropathy is one of the major complications of diabetes mellitus, leading to painful condition as neuropathic pain. The pathogenetic mechanism of diabetic peripheral neuropathy is very complex, and its understanding could lead to a more suitable therapeutic strategy. In this work, we analyzed the effects of ammonium glycyrrhizinate, a derivate salt of glycyrrhizic acid, on an in vitro system, neuroblastoma cells line SH-SY5Y, and we observed that ammonium glycyrrhizinate was able to prevent cytotoxic effect and mitochondrial fragmentation after high-glucose administration. In an in vivo experiment, we found that a short-repeated treatment with ammonium glycyrrhizinate was able to attenuate neuropathic hyperalgesia in streptozotocin-induced diabetic mice. In conclusion, our results showed that ammonium glycyrrhizinate could ameliorate diabetic peripheral neuropathy, counteracting both in vitro and in vivo effects induced by high glucose, and might represent a complementary medicine for the clinical management of diabetic peripheral neuropathy.

scholarly journals Ellagic acid alleviates high glucose-induced podocyte and renal epithelial cell apoptosis and hyperglycemia-induced renal injury by regulating NF-κB/miR-150-3p/BCL2

2021 ◽  
Author(s):  
Ying Cai ◽  
Yong Xu ◽  
Qicheng Ni ◽  
Bei Guo ◽  
Sheng Chen ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
High Glucose ◽  
Ellagic Acid ◽  
Interstitial Fibrosis ◽  
Cell Model ◽  
Intragastric Administration ◽  
Diabetic Mice ◽  
Glomerular Injury

Abstract Objective Ellagic acid (EA) as a multi-target bioactive compound has been reported to improve diabetes-related complications, including diabetic nephropathy (DN). Herein, we plan to investigate the molecular mechanism underlying EA-mediated renal protection in diabetic mice. Methods Streptozotocin (STZ; 35 mg/kg successive injection for 5 times) was applied to establish DN model in mice. Normal or diabetic mice were administrated by EA (100 mg/kg/day) by intragastric administration for 8 weeks. In vitro diabetic cell model, podocytes and renal tubular epithelial cells (RTECs) were exposed to normal glucose (NG; 5 mM) or high glucose (HG; 30 mM). Results Our results demonstrated that EA treatment prevented HG-induced podocyte and RTEC apoptosis and growth inhibition by inhibiting NF-κB/miR-150-3p to activate BCL2 in vitro. In vivo diabetic model of mice, EA administration improved renal filtration function, tubular and glomerular injury, and interstitial fibrosis. More importantly, supplementation of EA also suppressed NF-κB/miR-150-3p activation and accelerated BCL2 expression in the kidney of diabetic mice. In another experiment, miR-150-3p antagomir as a potential gene therapeutic choice has been validated to rescue hyperglycemia-induced renal dysfunction in mouse model. Taken together, in vitro and in vivo experimental measurements corroborate that EA modulates NF-κB/miR-150-3p/BCL2 cascade signaling to attenuate renal damage in diabetic models. Conclusion Our findings revealed that EA modulated the suppression of NF-κB/miR-150-3p to activate BCL2 that contributed to prevent hyperglycemia-induced renal dysfunction. In addition, synthetic miR-150-3p antagomir or inhibitors could alleviate tubular injury and interstitial fibrosis, and prevent HG-induced podocyte and RTEC apoptosis.

scholarly journals The effects of high glucose condition on rat tenocytesin vitroand rat Achilles tendonin vivo

2018 ◽  
Vol 7 (5) ◽  
pp. 362-372 ◽  
Author(s):  
Y. Ueda ◽  
A. Inui ◽  
Y. Mifune ◽  
R. Sakata ◽  
T. Muto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Achilles Tendon ◽  
High Glucose ◽  
Type I Collagen ◽  
Diabetic Rats ◽  
Type I ◽  
High Glucose Condition ◽  
Glucose Condition

ObjectivesThe aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy.MethodsUsing tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined.ResultsIn tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased.ConclusionThis study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint Res 2018;7:362–372. DOI: 10.1302/2046-3758.75.BJR-2017-0126.R2

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