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Sorbitol AND hyperglycemia

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
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)...
August 3, 2016: European Journal of Nutrition
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
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
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...
2016: Scientific Reports
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
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...
April 8, 2016: European Journal of Nutrition
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
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
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
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
Anson Snow, Biehuoy Shieh, Kun-Che Chang, Arttatrana Pal, Patricia Lenhart, David Ammar, Philip Ruzycki, Suryanarayana Palla, G Bhanuprakesh Reddy, J Mark Petrash
Aldose reductase (AR) is thought to play a role in the pathogenesis of diabetic eye diseases, including cataract and retinopathy. However, not all diabetics develop ocular complications. Paradoxically, some diabetics with poor metabolic control appear to be protected against retinopathy, while others with a history of excellent metabolic control develop severe complications. These observations indicate that one or more risk factors may influence the likelihood that an individual with diabetes will develop cataracts and/or retinopathy...
June 5, 2015: Chemico-biological Interactions
Madhoosudan A Patil, Palla Suryanarayana, Uday Kumar Putcha, Myadara Srinivas, G Bhanuprakash Reddy
Type 2 diabetes (T2D) generally follows prediabetes (PD) conditions such as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Although studies reported an association of IGT or IFG with cataract, the experimental basis for PD associated cataract is not known. Hence, we evaluated neonatal streptozotocin (nSTZ) induced rat model to study PD associated cataractogenesis by injecting STZ to two-day old rats. While majority (70%) of nSTZ injected pups developed IGT (nSTZ-PD) by two months but not cataract even after seven months, remaining (30%) nSTZ rats developed hyperglycemia (nSTZ-D) by two months and mature cataract by seven months...
2014: Oxidative Medicine and Cellular Longevity
Kun-Che Chang, Anson Snow, Daniel V LaBarbera, J Mark Petrash
Chronic hyperglycemia is an important risk factor involved in the onset and progression of diabetic retinopathy (DR). Among other effectors, aldose reductase (AR) has been linked to the pathogenesis of this degenerative disease. The purpose of this study was to investigate whether the novel AR inhibitor, beta-glucogallin (BGG), can offer protection against various hyperglycemia-induced abnormalities in human adult retinal pigment epithelial (ARPE-19) cells. AR is an enzyme that contributes to cellular stress by production of reactive oxygen species (ROS) under high glucose conditions...
June 5, 2015: Chemico-biological Interactions
M M Stecker, M R Stevenson
Hyperglycemia accentuates the injury produced by anoxia both in the central and peripheral nervous system. To understand whether this is a consequence of changes in metabolic pathways produced by anoxia, the effect of the metabolic substrate used by the rat peripheral nerve on the nerve action potential (NAP) was studied in the presence and absence of anoxia. In the continuously oxygenated state, the NAP was well preserved with glucose, lactate, as well as with high concentrations of sorbitol and fructose but not β-hydroxybutyrate, acetate or galactose...
January 22, 2015: Neuroscience
M K N Sai Varsha, Thiagarajan Raman, Ramar Manikandan
This study investigated the potential of vitamin K1 against streptozotocin-induced diabetic cataract in Wistar rats. A single, intraperitoneal injection of streptozotocin (STZ) (35 mg/kg) resulted in hyperglycemia, accumulation of sorbitol and formation of advanced glycation end product (AGE) in eye lens. Hyperglycemia in lens also resulted in superoxide anion and hydroxyl radical generation and less reduced glutathione suggesting oxidative stress in lens. Hyperglycemia also resulted in increase in lens Ca2+ and significant inhibition of lens Ca2+ ATPase activity...
November 2014: Experimental Eye Research
Jin Lee, Hae-In Lee, Kown-Il Seo, Hyun Wook Cho, Myung-Joo Kim, Eun-Mi Park, Mi-Kyung Lee
Ursolic acid (UA) is a pentacyclic triterpenoid compound that naturally occurs in fruits, leaves and flowers of medicinal herbs. This study investigated the dose-response efficacy of UA (0.01 and 0.05%) on glucose metabolism, the polyol pathway and dyslipidemia in streptozotocin/nicotinamide-induced diabetic mice. Supplement with both UA doses reduced fasting blood glucose and plasma triglyceride levels in non-obese type 2 diabetic mice. High-dose UA significantly lowered plasma free fatty acid, total cholesterol and VLDL-cholesterol levels compared with the diabetic control mice, while LDL-cholesterol levels were reduced with both doses...
July 2014: Indian Journal of Experimental Biology
Ashok K Tiwari, D Anand Kumar, Pisupati S Sweeya, H Anusha Chauhan, V Lavanya, K Sireesha, K Pavithra, Amtul Zehra
OBJECTIVE: Hyperglycemia induced generation of free radicals and consequent development of oxidative stress by polyol pathway is one of the crucial mechanisms stirring up development of diabetic complications. We evaluated influence of ten vegetables' juice on polyol pathway along with their antioxidant and antioxidative stress potentials. MATERIALS AND METHODS: Aldose reductase activity was determined utilising goat lens and human erythrocytes. In goat lens, utilization of nicotinamine adenine dinucleotide phosphate (NADPH) and aldose reductase inhibition was assayed...
April 2014: Pharmacognosy Magazine
Go Woon Kim, Sung Hyun Chung
Treatment of type 2 diabetes mellitus (T2DM) continues to present challenges, with many patients failing to achieve glycemic targets. Despite the availability of many oral and injectable anti-diabetic agents, therapeutic efficacy is often offset by undesirable side effects such as hypoglycemia, weight gain and cardiovascular complications. Therefore, the search for new therapeutic agents with an improved benefit-risk profile continues. Recent research has focused on the kidney as a potential therapeutic target, especially because maximal renal glucose reabsorption is increased in T2DM...
August 2014: Archives of Pharmacal Research
Lei Sun, De-Jing Shi, Xiang-Chun Gao, Shu-Yong Mi, Ying Yu, Qing Han
The present study was designed to investigate the effect of vanadium in alloxan-induced diabetes and cataract in rats. Different doses of vanadium was administered once daily for 8 weeks to alloxan-induced diabetic rats. To know the mechanism of action of vanadium, lens malondialdehyde (MDA), protein carbonyl content, activity of superoxide dismutase (SOD), activities of aldose reductase (AR), and sorbitol levels were assayed, respectively. Supplementation of vanadium to alloxan-induced diabetic rats decreased the blood glucose levels due to hyperglycemia, inhibited the AR activity, and delayed cataract progression in a dose-dependent manner...
May 2014: Biological Trace Element Research
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