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High Glucose Levels (high + glucose_level)

Distribution by Scientific Domains

Medical Sciences	57%
Life Sciences	35%

Selected Abstracts

High glucose increase cell cycle regulatory proteins level of mouse embryonic stem cells via PI3-K/Akt and MAPKs signal pathways

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2006
Yun Hee Kim
This study examined the effects of high glucose on cell proliferation and its related signal pathways using mouse embryonic stem (ES) cells. Here, we showed that high glucose level significantly increased [3H]thymidine incorporation, BrdU incorporation, the number of cells, [3H]leucine, and [3H]proline incorporation in a time-(>3 hr) and dose-(>25 mM) dependent manner. Moreover, high glucose level increased the cellular reactive oxygen species (ROS), Akt, and mitogen-activated protein kinases (MAPKs) phosphorylation. Subsequently, these signaling molecules involved in high glucose-induced increase of [3H]thymidine incorporation. High glucose level also increased cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4 protein levels, which is cell cycle regulatory proteins acting in G1,S phase of cell cycle. Inhibition of phosphatidylinositol 3-kinase (PI3-K) (LY 294002: PI3-kinase inhibitor, 10,6 M), Akt (Akt inhibitor, 10,5 M), and p44/42 MAPKs (PD 98059: MEK inhibitor, 10,5 M) decreased these proteins. High glucose level phosphorylated the RB protein, which was decreased by inhibition of PI3-K and Akt. In conclusion, high glucose level stimulates mouse ES cell proliferation via the PI3-K/Akt and MAPKs pathways. J. Cell. Physiol. 209: 94,102, 2006. © 2006 Wiley-Liss, Inc. [source]

High glucose levels enhance platelet activation: involvement of multiple mechanisms

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2006
Dzana Sudic
Summary Diabetes mellitus (DM) and hyperglycaemia are associated with platelet activation. The present study was designed to investigate how high glucose levels influence platelet function. Fasting human blood was incubated with different concentrations of d -glucose (5, 15 and 30 mmol/l) and other sugars without or with in vitro stimuli. Platelet activation was monitored by whole blood flow cytometry. High glucose levels enhanced adenosine diphosphate (ADP)- and thrombin receptor-activating peptide (TRAP)-induced platelet P-selectin expression, and TRAP-induced platelet fibrinogen binding. Similar effects were seen with 30 mmol/l l -glucose, sucrose and galactose. Hyperglycaemia also increased TRAP-induced platelet-leucocyte aggregation. Protein kinase C (PKC) blockade did not counteract the enhancement of platelet P-selectin expression, but abolished the enhancement of TRAP-induced platelet fibrinogen binding by hyperglycaemia. Superoxide anion scavenging by superoxide dismutase (SOD) attenuated the hyperglycaemic enhancement of platelet P-selectin expression, but did not counteract the enhancement of TRAP-induced platelet fibrinogen binding. Hyperglycaemia did not alter platelet intracellular calcium responses to agonist stimulation. Blockade of cyclo-oxygenase (COX), phosphotidylinositol-3 (PI3) kinase, or nitric oxide synthase, or the addition of insulin did not influence the effect of hyperglycaemia. In conclusion, high glucose levels enhanced platelet reactivity to agonist stimulation through elevated osmolality. This occurred via superoxide anion production, which enhanced platelet P-selectin expression (secretion), and PKC signalling, which enhanced TRAP-induced fibrinogen binding (aggregablity). [source]

Influence of perioperative blood glucose levels on outcome after infrainguinal bypass surgery in patients with diabetes

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2006
J. Malmstedt
Background: High glucose levels are associated with increased morbidity and mortality after coronary surgery and in intensive care. The influence of perioperative hyperglycaemia on the outcome after infrainguinal bypass surgery among diabetic patients is largely unknown. The aim was to determine whether high perioperative glucose levels were associated with increased morbidity after infrainguinal bypass surgery. Methods: Ninety-one consecutive diabetic patients undergoing primary infrainguinal bypass surgery were identified from a prospective vascular registry. Risk factors, indication for surgery, operative details and outcome data were extracted from the medical records. Exposure to perioperative hyperglycaemia was measured using the area under the curve (AUC) method; the AUC was calculated using all blood glucose readings during the first 48 h after surgery. Results: Multivariable analysis showed that the AUC for glucose (odds ratio (OR) 13·35, first versus fourth quartile), renal insufficiency (OR 4·77) and infected foot ulcer (OR 3·38) was significantly associated with poor outcome (death, major amputation or graft occlusion at 90 days). Similarly, the AUC for glucose (OR 14·45, first versus fourth quartile), female sex (OR 3·49) and tissue loss as indication (OR 3·30) was associated with surgical wound complications at 30 days. Conclusion: Poor perioperative glycaemic control was associated with an unfavourable outcome after infrainguinal bypass surgery in diabetic patients. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]

High glucose increase cell cycle regulatory proteins level of mouse embryonic stem cells via PI3-K/Akt and MAPKs signal pathways

Altered arachidonic acid biosynthesis and antioxidant protection mechanisms in Schwann cells grown in elevated glucose

JOURNAL OF NEUROCHEMISTRY, Issue 6 2002
Cristinel Mîinea
Abstract In cultured Schwann cells, elevated glucose induces alterations in arachidonic acid metabolism that cause a decrease in the content of glycerophospholipid arachidonoyl-containing molecular species (ACMS). This could result from decreased de novo arachidonic acid biosynthesis, or increased arachidonic acid release from phospholipids. Incorporation of radioactive 8,11,14-eicosatrienoic acid into ACMS was lower for cells grown in 30 mm versus 5 mm glucose, consistent with a decrease in ,5 desaturase activity. However, neither basal arachidonic acid release from prelabeled cells nor stimulated generation of arachidonic acid in the presence of the reacylation inhibitor, thimerosal, the phosphotyrosine phosphatase inhibitor, bipyridyl peroxovanadium, or both together, were altered by varying the glucose concentrations, indicating that arachidonic acid turnover did not contribute to ACMS depletion. Free cytosolic NAD+/NADH decreased, whereas NADP+/NADPH remained unchanged for cells grown in elevated glucose, implying that decreased desaturase activity is a result of metabolic changes other than cofactor availability. Schwann cells in elevated glucose were susceptible to oxidative stress, as shown by increased malondialdehyde, depleted glutathione levels, and reduced cytosolic superoxide dismutase activity. Glutathione-altering compounds had no effect on ACMS levels, in contrast to N -acetylcysteine and ,-lipoic acid, which partly corrected ACMS depletion in phosphatidylcholine. These findings suggest that in the Schwann cell cultures, a high glucose level elicits oxidative stress and weakens antioxidant protection mechanisms which could decrease arachidonic acid biosynthesis and that this deficit can be partly corrected by treatment with exogenous antioxidants. [source]

Imidazoline-induced amplification of glucose- and carbachol-stimulated insulin release includes a marked suppression of islet nitric oxide generation in the mouse

ACTA PHYSIOLOGICA, Issue 3 2009
S. Meidute-Abaraviciene
Abstract Aim:, The role of islet nitric oxide (NO) production in insulin-releasing mechanisms is unclear. We examined whether the beneficial effects of the imidazoline derivative RX 871024 (RX) on ,-cell function might be related to perturbations of islet NO production. Methods:, Experiments were performed with isolated islets or intact mice challenged with glucose or carbachol with or without RX treatment. Insulin was determined with radioimmunoassay, NO generation with high-performance liquid chromatography and expression of inducible NO synthase (iNOS) with confocal microscopy. Results:, RX treatment, in doses lacking effects on basal insulin, greatly amplified insulin release stimulated by the NO-generating secretagogues glucose and carbachol both in vitro and in vivo. RX also improved the glucose tolerance curve. Islets incubated at high glucose levels (20 mmol L,1) displayed increased NO production derived from both neuronal constitutive NO synthase (ncNOS) and iNOS. RX abrogated this glucose-induced NO production concomitant with amplification of insulin release. Confocal microscopy revealed abundant iNOS expression in , cells after incubation of islets at high but not low glucose levels. This was abolished after RX treatment. Similarly, islets cultured for 24 h at high glucose levels showed intense iNOS expression in , cells. This was abrogated with RX and followed by an amplified glucose-induced insulin release. Conclusion:, RX effectively counteracts the negative impact of ,-cell NO generation on insulin release stimulated by glucose and carbachol suggesting imidazoline compounds by virtue of NOS inhibitory properties being of potential therapeutic value for treatment of ,-cell dysfunction in hyperglycaemia and type 2 diabetes. [source]

Social consumption of alcohol in adolescents with Type 1 diabetes is associated with increased glucose lability, but not hypoglycaemia

DIABETIC MEDICINE, Issue 8 2006
D. Ismail
Abstract Aims To determine the effects of social consumption of alcohol by diabetic adolescents on glycaemic control. Methods Fourteen (five male) patients aged > 16 years were recruited from the diabetes clinic at the Royal Children's Hospital. The continuous glucose monitoring system (CGMS) was attached at a weekend when alcohol consumption was planned for one night only. For each patient, the 12-h period from 18.00 h to 06.00 h for the night with alcohol consumption (study period) was compared with the same period with non-alcohol consumption (control period) either 24 h before or after the alcohol study night. Thus, each subject was his/her own control. Glycaemic outcomes calculated from continuous glucose monitoring included mean blood glucose (MBG), percentage of time spent at low glucose levels (CGMS < 4.0 mmol/l), normal glucose levels (CGMS 4.0,10.0 mmol/l) and high glucose levels (> 10.0 mmol/l) and continuous overall net glycaemic action (CONGA). Results The mean number of standard alcohol drinks consumed during the study period was 9.0 for males and 6.3 for females. There was no difference in percentage of time at high and normal glucose levels in the study and control periods. During the control period, there was a higher percentage of time with low glucose levels compared with the study period (P < 0.05). There was an increased level of glycaemic variation during the study time when compared with the control period. Conclusions In an uncontrolled, social context, moderately heavy alcohol consumption by adolescents with Type 1 diabetes appears to be associated with increased glycaemic variation, but not with low glucose levels. [source]

High glucose levels upregulate upstream stimulatory factor 2 gene transcription in mesangial cells

JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008
Lihua Shi
Abstract Previously, we demonstrated that upstream stimulatory factor 2 (USF2) mediates high glucose-induced thrombospondin1 (TSP1) gene expression and TGF-, activity in glomerular mesangial cells and plays a role in diabetic renal complications. In the present studies, we further determined the molecular mechanisms by which high glucose levels regulate USF2 gene expression. In primary rat mesangial cells, we found that glucose treatment time and dose-dependently up-regulated USF2 expression (mRNA and protein). By using cycloheximide to block the de novo protein synthesis, similar rate of USF2 degradation was found under either normal glucose or high glucose conditions. USF2 mRNA stability was not altered by high glucose treatment. Furthermore, high glucose treatment stimulated USF2 gene promoter activity. By using the luciferase-promoter deletion assay, site-directed mutagenesis, and transactivation assay, we identified a glucose-responsive element in the USF2 gene promoter (,1,740 to ,1,620, relative to the transcription start site) and demonstrated that glucose-induced USF2 expression is mediated through a cAMP-response element-binding protein (CREB)-dependent transactivation of the USF2 promoter. Furthermore, siRNA-mediated CREB knock down abolished glucose-induced USF2 expression. Taken together, these data indicate that high glucose levels up-regulate USF2 gene transcription in mesangial cells through CREB-dependent transactivation of the USF2 promoter. J. Cell. Biochem. 103: 1952,1961, 2007. © 2007 Wiley-Liss, Inc. [source]

Small Amounts of Dietary Fructose Dramatically Increase Hepatic Glucose Uptake Through a Novel Mechanism of Glucokinase Activation

NUTRITION REVIEWS, Issue 8 2002
Article first published online: 16 SEP 200
Glucokinase plays a major role in the control of hepatic glucose uptake and storage as glycogen. Small amounts of fructose-1-phosphate, in the presence of relatively high glucose levels, markedly stimulate glucokinase through a novel mechanism of regulation involving dissociation from a regulatory protein and translocation from the nucleus into the cytosol. Using this understanding of glucokinase regulation, a recent study demonstrated that very small amounts of fructose (infused into the duodenum) could increase hepatic glucose uptake and glycogen storage, and reduce peripheral glycemia and insulin levels in the dog. These results suggest that very small amounts of dietary fructose could be beneficial in type 2 diabetes. [source]

Evaluation of the SELDI-TOF MS technique for protein profiling of pancreatic islets exposed to glucose and oleate

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 17 2007
Henrik Ortsäter Dr.
Abstract The aim of the study was to evaluate the SELDI-TOF MS technique for pancreatic islet research. Mouse islets were cultured at low or high glucose levels in the absence or presence of oleate and characterized by measuring insulin secretion and oxygen tension. Subsequently, the islets were protein profiled. Up to 200 different peaks could be detected in a single experiment with the majority of peaks corresponding to proteins with masses below 30,kDa. By combining different protein arrays, the number of detected peaks could be increased further. The optimal binding of islet proteins was achieved using the anionic exchange array and phosphate buffer (pH,6) when the binding of insulin was low, which allowed other less abundant proteins to be captured. When islets from different culture conditions were profiled and analyzed, in total 25 proteins were found to be oleate/glucose-regulated. An oleate-regulated protein was chosen for identification work, which was conducted by passive elution from SDS-PAGE gels and subsequent in-gel trypsin digestion and MALDI-TOF MS. The protein was identified as peptidyl-prolyl isomerase B (PPI-B). In conclusion, the study demonstrates that SELDI-technique can be used not only to obtain islet protein patterns but is also helpful in the subsequent identification of differentially expressed proteins. [source]

High glucose levels enhance platelet activation: involvement of multiple mechanisms

High insulin levels are positively associated with peripheral nervous system function

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009
H. Isojärvi
Objective,,, The aim of this study was to analyze peripheral nervous system (PNS) function in overweight and obese individuals. Materials and Methods,,, Forty-four adult non-diabetic overweight individuals were recruited. Peroneal motor nerve conduction and radial, sural, and medial plantar sensory nerve conduction were studied. Insulin and glucose levels were determined twice (over a 2- to 3-year period) with an oral glucose tolerance test (OGTT). Multiple stepwise linear regression models adjusted for age, height, weight, and skin temperature were used to analyze the data. Results,,, Analysis revealed that baseline insulin levels measured 120 min after an OGTT explained 18% of the variation in peroneal F -wave minimum latency, 8% of peroneal F -wave maximum latency variation, 15% of sural sensory latency variation, 13% of sural sensory nerve conduction velocity (NCV) variation, and 10% of the variation in medial plantar sensory NCV. Discussion and Conclusion,,, Our study shows that serum insulin levels measured 120 min after an OGGT are positively associated with PNS function. High insulin levels without notably high glucose levels appear to be beneficial for the function of the PNS. [source]

Antioxidants reduce diabetic damage in bovine lenses in culture

ACTA OPHTHALMOLOGICA, Issue 2009
A DOVRAT
Purpose Background: There are several theories regarding possible mechanisms leading to diabetic cataract. Few of them include oxidation stress. Aims: Investigation of the mechanisms of cataract formation under diabetic conditions, and examination of the effects of N-acetyl-L-cysteine (NAC), (which is a precursor of glutathione and an anti-inflammatory agent) and derivatives of Desferrioxamine (DFO)(which is an iron chelator and reduces oxidative stress) on diabetic cataract. Methods The experiments included 78 bovine lenses. The lenses were divided into eight different treatments including controls and lenses incubated with high glucose levels (450 mg %) with or without each one of the antioxidants. The intact lenses were incubated for a period of two weeks in our special organ culture conditions. Lens optical quality was analyzed every 24 hours. At the end of the culture period, oxidation was followed in the lens epithelial cells with dichlorofluorescein assay and lens proteins were analyzed by SDS and 2D gel electrophoresis. Results High levels of glucose in the culture medium caused optical damage to bovine lenses, increased lens volume due to swelling, increased oxidation of lens epithelial cells, and caused changes in lens beta crystallin. The anti-oxidants reduced this damage. NAC and Zn-DFO protected the lenses better than DFO. Conclusion Antioxidants can protect the lens from high glucose damage. This study was supported in part by a grant from the Esther and Chaim Coppel Trust and by the Guzik Ophthalmology Research Fund [source]