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Sorbitol AND diabetes

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https://www.readbyqxmd.com/read/28516783/antidiabetic-disruptors-of-the-glucokinase-glucokinase-regulatory-protein-complex-reorganize-a-coulombic-interface
#1
Juliana Martinez, Qing Xiao, Armen Zakarian, Brian G Miller
The glucokinase regulatory protein (GKRP) plays an essential role in glucose homeostasis by acting as a competitive inhibitor of glucokinase (GCK) and triggering its localization to the hepatocyte nucleus upon glucose deprivation. Metabolites such as fructose 6-phosphate and sorbitol 6-phosphate promote assembly of the GCK-GKRP complex, whereas fructose 1-phosphate and functionalized piperazines with potent in vivo antidiabetic activity disrupt the complex. Here, we establish the molecular basis by which these natural and synthetic ligands modulate the GCK-GKRP interaction...
May 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28452488/metabolomics-study-of-the-effects-of-inflammation-hypoxia-and-high-glucose-on-isolated-human-pancreatic-islets
#2
Marta Garcia-Contreras, Alejandro Tamayo-Garcia, Kirk L Pappan, Gregory A Michelotti, Cherie L Stabler, Camillo Ricordi, Peter Buchwald
The transplantation of human pancreatic islets is a therapeutic possibility for a subset of type 1 diabetic patients who experience severe hypoglycemia. Pre- and post-transplantation loss in islet viability and function, however, is a major efficacy-limiting impediment. To investigate the effects of inflammation and hypoxia, the main obstacles hampering the survival and function of isolated, cultured, and transplanted islets, we conducted a comprehensive metabolomics evaluation of human islets in parallel with dynamic glucose-stimulated insulin release (GSIR) perifusion studies for functional evaluation...
May 9, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#3
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...
April 24, 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
#4
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/28302016/validation-of-tzd-scaffold-as-potential-aris-pharmacophore-modelling-atom-based-3d-qsar-and-docking-studies
#5
Lalita Dahiya, Manoj Kumar Mahapatra, Ramandeep Kaur, Vipin Kumar, Manoj Kumar
Metabolic disorders associated with diabetic patients are a serious concern. Aldose reductase (ALR2) has been identified as first rate-limiting enzyme in the polyol pathway which catalyzes the reduction of glucose to sorbitol. It represents one of the validated targets to develop potential new chemical entities for the prevention and subsequent progression of microvascular diabetic complications. In order to further understand the intricate structural prerequisites of molecules to act as ALR2 inhibitors, ligand-based pharmacophore model, atom-based 3D-QSAR and structure based drug design studies have been performed on a series of 2,4-thiazolidinedione derivatives with ALR2 inhibitory activity...
March 15, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28259841/enhancing-activity-and-selectivity-in-a-series-of-pyrrol-1-yl-1-hydroxypyrazole-based-aldose-reductase-inhibitors-the-case-of-trifluoroacetylation
#6
Nikolaos Papastavrou, Maria Chatzopoulou, Jana Ballekova, Mario Cappiello, Roberta Moschini, Francesco Balestri, Alexandros Patsilinakos, Rino Ragno, Milan Stefek, Ioannis Nicolaou
Aldose reductase (ALR2) has been the target of therapeutic intervention for over 40 years; first, for its role in long-term diabetic complications and more recently as a key mediator in inflammation and cancer. However, efforts to prepare small-molecule aldose reductase inhibitors (ARIs) have mostly yielded carboxylic acids with rather poor pharmacokinetics. To address this limitation, the 1-hydroxypyrazole moiety has been previously established as a bioisostere of acetic acid in a group of aroyl-substituted pyrrolyl derivatives...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28239653/the-human-brain-produces-fructose-from-glucose
#7
Janice J Hwang, Lihong Jiang, Muhammad Hamza, Feng Dai, Renata Belfort-DeAguiar, Gary Cline, Douglas L Rothman, Graeme Mason, Robert S Sherwin
Fructose has been implicated in the pathogenesis of obesity and type 2 diabetes. In contrast to glucose, CNS delivery of fructose in rodents promotes feeding behavior. However, because circulating plasma fructose levels are exceedingly low, it remains unclear to what extent fructose crosses the blood-brain barrier to exert CNS effects. To determine whether fructose can be endogenously generated from glucose via the polyol pathway (glucose → sorbitol → fructose) in human brain, 8 healthy subjects (4 women/4 men; age, 28...
February 23, 2017: JCI Insight
https://www.readbyqxmd.com/read/28208627/phytochemical-analysis-of-agrimonia-pilosa-ledeb-its-antioxidant-activity-and-aldose-reductase-inhibitory-potential
#8
Set Byeol Kim, Seung Hwan Hwang, Hong-Won Suh, Soon Sung Lim
The aim of this study was to determine aldose reductase (AR) inhibitory activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of compounds from Agrimonia pilosa Ledeb (AP). We isolated agrimoniin (AM), four flavonoid glucosides and two flavonoid glucuronides from the n-butanol fraction of AP 50% methanol extract. In addition to isolated compounds, the AR-inhibitory activity and the DPPH free radical scavenging activity of catechin, 5-flavonoids, and 4-flavonoid glucosides (known components of AP) against rat lens AR (RLAR) and DPPH assay were measured...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28177738/sorbitol-increases-muscle-glucose-uptake-ex-vivo-and-inhibits-intestinal-glucose-absorption-ex-vivo-and-in-normal-and-type-2-diabetic-rats
#9
Chika Ifeanyi Chukwuma, Md Shahidul Islam
Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50 = 14...
December 12, 2016: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28153595/phenolic-compounds-the-inhibition-effect-on-polyol-pathway-enzymes
#10
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
#11
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/28035619/inflammation-oxidative-stress-apoptosis-and-autophagy-in-diabetes-mellitus-and-diabetic-kidney-disease-the-four-horsemen-of-the-apocalypse
#12
REVIEW
Kultigin Turkmen
Diabetic kidney disease (DKD) can occur in approximately 30-40% of both type 1 and type 2 diabetic patients. The well-established features of DKD include increased serum glucose levels along with chronic low-grade inflammation, OxS, increased advanced glycation end products, sorbitol accumulation, increased hexosamine, and protein kinase C pathway activation. On the other hand, accumulating evidence suggests that novel pathways including apoptosis and autophagy might also play important roles in the pathogenesis and progression of DKD...
May 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/27894247/aldose-reductase-as-a-drug-target-for-treatment-of-diabetic-nephropathy-promises-and-challenges
#13
REVIEW
Heba ElGamal, Shankar Munusamy
Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively nonmetabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney...
2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27835059/epalrestat-an-aldose-reductase-inhibitor-prevents-glucose-induced-toxicity-in-human-retinal-pigment-epithelial-cells-in-vitro
#14
Srinivasan Senthilkumari, Rajendran Sharmila, Gowripriya Chidambaranathan, Ayyasamy Vanniarajan
PURPOSE: Aldose reductase (ALR), the first and rate-limiting enzyme involved in polyol pathway plays a central role in diabetes and its related complications, including diabetic retinopathy (DR). Inhibition of ALR may also be an ideal target for reducing the deleterious effects of DR. Therefore, the purpose of the present study was to investigate the protective effect of epalrestat (EPL), ALR inhibitor on glucose-induced toxicity in ARPE-19 cells. METHODS: ARPE-19 cells were challenged with normal glucose (NG, 5 mM) and high glucose (HG1, 25 mM and HG2, 50 mM) in the presence or absence of EPL...
January 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27628063/osmotic-expression-of-aldose-reductase-in-retinal-pigment-epithelial-cells-involvement-of-nfat5
#15
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/27520089/investigation-of-synergistic-mechanism-and-identification-of-interaction-site-of-aldose-reductase-with-the-combination-of-gigantol-and-syringic-acid-for-prevention-of-diabetic-cataract
#16
Jie Wu, Xue Li, Hua Fang, Yanqun Yi, Dan Chen, Yan Long, Xinxin Gao, Xiaoyong Wei, C-Y Oliver Chen
BACKGROUND: Gigantol and syringic acid (SA) have been shown to synergistically prevent formation of diabetic cataract (DC). However, the exact mechanism of this effect is unknown. Here, we investigate the effect of these compounds on the activity of aldose reductase (AR) and cataract formation. METHODS: We examined the synergistic anti-cataract efficacy of gigantol and SA in the high glucose- and streptozotocin -induced DC rat model; synergism was evaluated using Jin's formula...
August 12, 2016: BMC Complementary and Alternative Medicine
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
#17
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
https://www.readbyqxmd.com/read/27465797/activation-of-general-control-nonderepressible-2-kinase-protects-human-glomerular-endothelial-cells-from-harmful-high-glucose-induced-molecular-pathways
#18
Theodoros Eleftheriadis, Konstantina Tsogka, Georgios Pissas, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
PURPOSE: Considering the referred beneficial effects of protein restriction on diabetic nephropathy (DN) and the role of renal endothelium in its pathogenesis, we evaluated the effect of general control nonderepressible 2 (GCN2) kinase activation, a sensor of amino acid deprivation, on known detrimental molecular pathways in primary human glomerular endothelial cells (GEnC). METHODS: GEnC were cultured under normal or high-glucose conditions in the presence or not of the GCN2 kinase activator, tryptophanol...
October 2016: International Urology and Nephrology
https://www.readbyqxmd.com/read/27415159/zolfino-landrace-phaseolus-vulgaris-l-from-pratomagno-general-and-specific-features-of-a-functional-food
#19
Francesco Balestri, Rossella Rotondo, Roberta Moschini, Mario Pellegrino, Mario Cappiello, Vito Barracco, Livia Misuri, Carlo Sorce, Andrea Andreucci, Antonella Del-Corso, Umberto Mura
BACKGROUND: The Zolfino bean is a variety of Phaseolus vulgaris, which is cultivated in a limited area of Tuscany, Italy, and is widely appreciated for its flavor and culinary uses. OBJECTIVES: A yellow Zolfino landrace cultivated in the Leccio-Reggello area was characterized and compared with three other varieties of Phaseolus vulgaris (i.e. the Borlotto, Cannellino, and Corona beans) in terms of its general features and potential as an antioxidant/anti-inflammatory agent...
2016: Food & Nutrition Research
https://www.readbyqxmd.com/read/27396410/structure-activity-relationship-study-reveals-benzazepine-derivatives-of-luteolin-as-new-aldose-reductase-inhibitors-for-diabetic-cataract
#20
Jomon Sebastian
Hyperglycaemia in diabetic patients causes diverse range of complications and the earliest among them is diabetic cataract. The role of aldose reductase, the key enzyme in polyol pathway, is well known in the genesis of cataract in chronic diabetic patients. Controlling of sorbitol flux into lens epithelial cells through aldose reductase inhibitors is an important treatment strategy. Due to the side-effects of many drugs so far developed, the development of aldose reductase inhibitors from natural sources has gained considerable attention...
June 30, 2016: Current Drug Discovery Technologies
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