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Sorbitol AND hyperglycemia

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https://www.readbyqxmd.com/read/29126968/jnk-signaling-pathway-regulates-sorbitol-induced-tau-proteolysis-and-apoptosis-in-sh-sy5y-cells-by-targeting-caspase-3
#1
Marta Olivera Santa-Catalina, Montaña Caballero Bermejo, Ricardo Argent, Juan C Alonso, Francisco Centeno, María J Lorenzo
Growing evidence suggests that Diabetes Mellitus increases the risk of developing Alzheimer's disease. It is well known that hyperglycemia, a key feature of Diabetes Mellitus, may induce plasma osmolarity disturbances. Both hyperglycemia and hyperosmolarity promote the altered post-translational regulation of microtubule-associated protein Tau. Interestingly, abnormal hyperphosphorylation and cleavage of Tau have been proven to lead to the genesis of filamentous structures referred to as neurofibrillary tangles, the main pathological hallmark of Alzheimer's disease...
November 7, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29017142/mechanisms-of-antidiabetic-effects-of-flavonoid-rutin
#2
REVIEW
Ahmad Ghorbani
Several lines of evidence suggest that flavonoids that originated from vegetables and medicinal plants have beneficial effects on diabetes by improving glycemic control, lipid profile, and antioxidant status. Rutin is a flavonoid found in many plants and shows a wide range of biological activities including anti-inflammatory, antioxidant, neuroprotective, nephroprotective, and hepatoprotective effects. In this review, the antihyperglycemic property of rutin and its protective effects against the development of diabetic complications are discussed...
October 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28842639/metabolomic-analysis-reveals-vitamin-d-induced-decrease-in-polyol-pathway-and-subtle-modulation-of-glycolysis-in-hek293t-cells
#3
G C Santos, J D Zeidler, J A Pérez-Valencia, A C B Sant'Anna-Silva, A T Da Poian, T El-Bacha, F C L Almeida
We combined (1)H NMR metabolomics with functional and molecular biochemical assays to describe the metabolic changes elicited by vitamin D in HEK293T, an embryonic proliferative cell line adapted to high-glucose concentrations. Activation of the polyol pathway, was the most important consequence of cell exposure to high glucose concentration, resembling cells exposed to hyperglycemia. Vitamin D induced alterations in HEK293T cells metabolism, including a decrease in sorbitol, glycine, glutamate, guanine. Vitamin D modulated glycolysis by increasing phosphoglycerate mutase and decreasing enolase activities, changing carbon fate without changing glucose consumption, lactate export and Krebs cycle...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820747/involvement-of-hyperglycemia-in-the-development-of-platelet-procoagulant-response-the-role-of-aldose-reductase-and-platelet-swelling
#4
Tomasz Rusak, Tomasz Misztal, Malgorzata Rusak, Justyna Branska-Januszewska, Marian Tomasiak
: Rise in mean platelet volume (MPV) has been demonstrated to be associated with increased platelet reactivity. In diabetes patients, augmented MPV was proposed to contribute to increased risk of thrombotic complications. Therefore, the aim of this study was to investigate whether under hyperglycemic conditions, aldose reductase (AR)-mediated sorbitol formation and associated rise in cell volume, which subsequently results in platelet hyperactivation. Platelets were obtained from 30 healthy volunteers and 13 patients with diabetes...
September 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28557170/phenolic-compounds-inhibit-the-aldose-reductase-enzyme-from-the-sheep-kidney
#5
Yeliz Demir, Mesut Işık, İlhami Gülçin, Şükrü Beydemir
Aldose reductase (AR) is the key enzyme for the polyol pathway and responsible for sorbitol accumulation during the hyperglycemia. The present article focuses on the role of phenol, pyrogallol, hydroquinone, resorcinol, catechol, and phloroglucinol in in vitro inhibition of AR. For this purpose, AR was purified from the sheep kidney with 5.33 EU mg(-1) specific activity and 0.64% yield using several chromatographic methods. Various concentrations of the compounds were tested on in vitro AR activity. IC50 values were found for phenol, pyrogallol, hydroquinone, resorcinol, catechol, and phloroglucinol as 6...
May 29, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#6
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28350848/reduction-of-oxidative-nitrosative-stress-underlies-anticataract-effect-of-topically-applied-tocotrienol-in-streptozotocin-induced-diabetic-rats
#7
Nurul Alimah Abdul Nasir, Renu Agarwal, Siti Hamimah Sheikh Abdul Kadir, Sushil Vasudevan, Minaketan Tripathy, Igor Iezhitsa, Aqil Mohammad Daher, Mohd Ikraam Ibrahim, Nafeeza Mohd Ismail
Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats...
2017: PloS One
https://www.readbyqxmd.com/read/28153595/phenolic-compounds-the-inhibition-effect-on-polyol-pathway-enzymes
#8
Hatice Esra Aslan, Şükrü Beydemir
The polyol pathway called as sorbitol way is a small part of glycose metabolism. The pathway is regarded as an important element in the pathogenesis of various diabetic complications in individuals with diabetes mellitus. The pathway plays a crucial role in hyperglycemia. The polyol pathway contains two enzymes as aldose reductase (AR) and sorbitol dehydrogenase (SDH). In the present study, AR and SDH were purified from sheep liver by using simple chromatographic methods. AR was purified with a yield of 2.11% and approximately 162 fold and SDH was purified with a yield of 0...
March 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28123632/effects-of-averrhoa-carambola-l-oxalidaceae-juice-mediated-on-hyperglycemia-hyperlipidemia-and-its-influence-on-regulatory-protein-expression-in-the-injured-kidneys-of-streptozotocin-induced-diabetic-mice
#9
Hoa Thi Thai Pham, Wansu Huang, Chuangye Han, Juman Li, Qiuqiao Xie, Jinbin Wei, Xiaohui Xu, Zefeng Lai, Xiang Huang, Renbin Huang, Qingwei Wen
Recently, many reports have shown that Averrhoa carambola L. (Oxalidaceae) juice (EACJ) could reduce blood glucose in humans. However, its mechanisms have not been well explored; therefore, our study aimed to investigate the beneficial effects of EACJ on hyperglycemia, hyperlipidemia and renal injury in streptozotocin (STZ)-induced diabetic mice. Those mice were injected with STZ via the tail vein (120 mg/kg body weight) and were identified as diabetic mice when the level of blood glucose was ≥ 11.1 mmol/L...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/27628063/osmotic-expression-of-aldose-reductase-in-retinal-pigment-epithelial-cells-involvement-of-nfat5
#10
Anica Winges, Tarcyane Barata Garcia, Philipp Prager, Peter Wiedemann, Leon Kohen, Andreas Bringmann, Margrit Hollborn
BACKGROUND: Diabetic retinopathy is associated with osmotic stress resulting from hyperglycemia and intracellular sorbitol accumulation. Systemic hypertension is a risk factor of diabetic retinopathy. High intake of dietary salt increases extracellular osmolarity resulting in systemic hypertension. We determined the effects of extracellular hyperosmolarity, chemical hypoxia, and oxidative stress on the gene expression of enzymes involved in sorbitol production and conversion in cultured human retinal pigment epithelial (RPE) cells...
December 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27488609/lutein-attenuates-oxidative-stress-markers-and-ameliorates-glucose-homeostasis-through-polyol-pathway-in-heart-and-kidney-of-stz-induced-hyperglycemic-rat-model
#11
Gurunathan Sharavana, G S Joseph, Vallikannan Baskaran
PURPOSE: Lutein's role on chronic hyperglycemia-induced oxidative stress and associated glucose homeostasis in heart and kidney is limited. Purpose of the study is to investigate the effect of lutein on cardiac and renal polyol pathway enzymes and oxidative stress markers under hyperglycemia-induced oxidative stress condition using streptozotocin (STZ)-injected rat model. METHODS: STZ-induced hyperglycemic (fasting blood glucose ≥11 mM) male Wistar rats were divided into two groups (n = 11/group)...
December 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/27365552/melatonin-reduces-cataract-formation-and-aldose-reductase-activity-in-lenses-of-streptozotocin-induced-diabetic-rat
#12
Marjan Khorsand, Masoumeh Akmali, Sahab Sharzad, Mojtaba Beheshtitabar
BACKGROUND: The relationship between the high activity of aldose reductase (AR) and diabetic cataract formation has been previously investigated. The purpose of the present study was to determine the preventing effect of melatonin on streptozotocin (STZ)-induced diabetic cataract in rats. METHODS: 34 adult healthy male Sprague-Dawely rats were divided into four groups. Diabetic control and diabetic+melatonin received a single dose of STZ (50 mg/kg, intraperitoneally), whereas the normal control and normal+melatonin received vehicle...
July 2016: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/27197688/polyol-accumulation-in-muscle-and-liver-in-a-mouse-model-of-type-2-diabetes
#13
Emily J Gallagher, Derek LeRoith, Marilyn Stasinopoulos, Zara Zelenko, Joseph Shiloach
AIMS: Type 2 diabetes (T2D) is a complex metabolic disease leading to complications in multiple organs. Diabetic myopathy and liver disease are common complications of T2D, but are incompletely understood. To gain insight into the pathogenesis of these conditions we performed metabolomic analysis of skeletal muscle and liver in a mouse model of T2D. METHODS: Tissue metabolomics were performed by GC/MS and LC/MS of the skeletal muscle and liver in the MKR mouse model of T2D, compared with control mice...
August 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27109517/bioactivity-focus-of-%C3%AE-cyano-4-hydroxycinnamic-acid-chca-leads-to-effective-multifunctional-aldose-reductase-inhibitors
#14
Laitao Zhang, Yi-Fang Li, Sheng Yuan, Shijie Zhang, Huanhuan Zheng, Jie Liu, Pinghua Sun, Yijun Gu, Hiroshi Kurihara, Rong-Rong He, Heru Chen
Bioactivity focus on α-cyano-4-hydroxycinnamic acid (CHCA) scaffold results in a small library of novel multifunctional aldose reductase (ALR2) inhibitors. All the entities displayed good to excellent inhibition with IC50 72-405 nM. (R,E)-N-(3-(2-acetamido-3-(benzyloxy)propanamido)propyl)-2-cyano-3-(4-hydroxy phenyl)acrylamide (5f) was confirmed as the most active inhibitor (IC50 72.7 ± 1.6 nM), and the best antioxidant. 5f bound to ALR2 with new mode without affecting the aldehyde reductase (ALR1) activity, implicating high selectivity to ALR2...
April 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27102270/aldose-reductase-ocular-diabetic-complications-and-the-development-of-topical-kinostat-%C3%A2
#15
REVIEW
Peter F Kador, Milton Wyman, Peter J Oates
Diabetes mellitus (DM) is a major health problem with devastating effects on ocular health in both industrialized and developing countries. The control of hyperglycemia is critical to minimizing the impact of DM on ocular tissues because inadequate glycemic control leads to ocular tissue changes that range from a temporary blurring of vision to permanent vision loss. The biochemical mechanisms that promote the development of diabetic complications have been extensively studied. As a result, a number of prominent biochemical pathways have been identified...
September 2016: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/27059477/consumption-of-polyphenol-rich-morus-alba-leaves-extract-attenuates-early-diabetic-retinopathy-the-underlying-mechanism
#16
Ayman M Mahmoud, Sanaa M Abd El-Twab, Eman S Abdel-Reheim
PURPOSE: Beneficial effects of white mulberry against diabetes mellitus have been reported. However, the molecular mechanisms of how white mulberry can attenuate diabetic retinopathy remain poorly understood. Here, the mechanism underlying the protective effect of Morus alba leaves ethanolic extract on oxidative stress, inflammation, apoptosis, and angiogenesis in diabetic retinopathy was investigated. METHODS: Diabetes was induced by injection of streptozotocin...
June 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/26544518/ameliorative-effects-of-thymoquinone-against-eye-lens-changes-in-streptozotocin-diabetic-rats
#17
Amr A Fouad, Fahad Alwadani
The possible protective effect of thymoquinone against eye lens changes in diabetic rats was investigated. Following diabetes induction by a single injection of streptozotocin (45 mg/kg, i.p.), thymoquinone was administered in three different doses (20, 40, and 80 mg/kg/day, p.o.) for 12 weeks. Thymoquinone significantly and dose-dependently attenuated the hypoinsulinemia and hyperglycemia in diabetic rats. Also, thymoquinone (particularly 40 and 80 mg/kg) significantly decreased the elevations of malondialdehyde, nitric oxide, tumor necrosis factor-α, glycated proteins, aldose reductase activity, sorbitol level, and caspase-3 activity in the lens tissues of diabetic rats...
November 2015: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/25998127/hyperglycemia-promotes-schwann-cell-de-differentiation-and-de-myelination-via-sorbitol-accumulation-and-igf1-protein-down-regulation
#18
Wu Hao, Syoichi Tashiro, Tomoka Hasegawa, Yuiko Sato, Tami Kobayashi, Toshimi Tando, Eri Katsuyama, Atsuhiro Fujie, Ryuichi Watanabe, Mayu Morita, Kana Miyamoto, Hideo Morioka, Masaya Nakamura, Morio Matsumoto, Norio Amizuka, Yoshiaki Toyama, Takeshi Miyamoto
Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression...
July 10, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25802544/litsea-japonica-extract-inhibits-aldose-reductase-activity-and-hyperglycemia-induced-lenticular-sorbitol-accumulation-in-db-db-mice
#19
Junghyun Kim, Chan-Sik Kim, Eunjin Sohn, Yun Mi Lee, Kyuhyung Jo, Jin Sook Kim
Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway. AR-dependent synthesis of excess polyols leads to lens opacification in diabetic cataract. The purpose of this study is to investigate the protective effect of Litsea japonica extract (LJE) on diabetes-induced lens opacification and its protective mechanism in db/db mice. Seven-week-old male db/db mice were treated with LJE (100 and 250 mg/kg body weight) once a day orally for 12 weeks. LJE dose dependently inhibited rat lens aldose reductase activity in vitro (IC50 = 13...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/25560570/h2s-donors-attenuate-diabetic-nephropathy-in-rats-modulation-of-oxidant-status-and-polyol-pathway
#20
Marwa M Safar, Rania M Abdelsalam
BACKGROUND: Sulfurous mineral water and its main active ingredient sodium hydrosulfide (NaHS) are major sources of H2S. The present study aimed to explore their protective effect on one of the serious long-term complications of diabetes; diabetic nephropathy. METHODS: Sulfurous mineral water (as drinking water), NaHS (14 μmol/kg/day; ip), and gliclazide (10mg/kg; po) were administered daily for 6 weeks to streptozotocin (STZ)-diabetic rats. RESULTS: STZ-induced diabetes was associated with body weight reduction, hyperglycemia, overproduction of glycated hemoglobin, as well as decline in serum insulin, C-peptide, and insulin like growth factor-I...
February 2015: Pharmacological Reports: PR
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