Relationship between Sucralose Consumption and Serum Concentration of Glycosylated Hemoglobin in People with Type 2 Diabetes Mellitus without Complications

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María del Carmen Cortés-López

2017-11-01

Full Text Available People who live with diabetes consume sucralose to control their blood glucose, but there is a controversy about this topic. To evaluate the relationship between sucralose consumption and serum concentration of glycosylated hemoglobin in people with Type 2 Diabetes Mellitus without complications. Cross-sectional study. Universe of 27 214 people with Type 2 Diabetes Mellitus without complications, users of a primary care unit from the Instituto Mexicano del Seguro Social in the state of Jalisco, Mexico. Simple probabilistic sample, n = 194 (p = 0,05. Propositive sampling. Selection criteria: adults of any gender and education level who agreed to participate. Variables: sociodemographic, anthropometric, clinical and dietary. Data collection instruments: Sociodemographic questionnaire, Tanita Fitscan© 585 scale, Tanita Fitscan© HR-200 stadiometer, Body Flex© tape-measure, Slim Guide© plicometer, Afinion© AS100 analyzer, and Frequency of Food Consumption Questionnaire. Information sources: clinical files and Mexican System of Equivalent Foods. Analysis: descriptive and inferential statistics (p ≤ 0,05. 194 people. Mean age 60,23 ± 11,16, interval 28-93 years. 56,2% females and 43,8% males. Difference between glycosilated hemoglobin means: sucralose consumers 7,5% ± 1,7%, no sucralose consumers 8,1% ± 2,1% (p < 0,01. Association force “sucralose consumption/high glycosilated hemoglobin concentration” OR = 1,42 (CI95% 0,63, 3,21. Lineal correlation “quarterly sucralose consumption/serum concentration of glycosylated hemoglobin” ρ = -0,754 (R2 = 0,0057, p = 0,333. This results were partially consistent to the pre-existing literature. Studies with representative stratified samples and control of dietary variables are required for better results.

Continuous glucose monitoring and its relationship to hemoglobin A1c and oral glucose tolerance testing in obese and prediabetic youth.

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Chan, Christine L; Pyle, Laura; Newnes, Lindsey; Nadeau, Kristen J; Zeitler, Philip S; Kelsey, Megan M

2015-03-01

The optimal screening test for diabetes and prediabetes in obese youth is controversial. We examined whether glycosylated hemoglobin (HbA1c) or the oral glucose tolerance test (OGTT) is a better predictor of free-living glycemia as measured by continuous glucose monitoring (CGM). This was a cross-sectional study of youth 10-18 years old, body mass index (BMI) 85th percentile or greater, with diabetes risk factors. Participants (n = 118) with BMI 85th percentile or greater, not on medications for glucose management, were recruited from primary care and pediatric endocrinology clinics around Denver, Colorado. HbA1c, fasting plasma glucose, and 2-hour glucose were collected and all participants wore a blinded CGM for 72 hours. CGM outcomes were determined and descriptive statistics calculated. Performance characteristics at current American Diabetes Association cutpoints were compared with CGM outcomes. CGM data were successfully collected on 98 obese youth. Those with prediabetes had significantly higher average glucose, area under the curve (AUC), peak glucose, and time greater than 120 and greater than 140 mg/dL (P obese youth, HbA1c and 2-hour glucose performed equally well at predicting free-living glycemia on CGM, suggesting that both are valid tests for dysglycemia screening.

Relationship between changes in hemoglobin glycosilated and improvement of body composition in patients with morbid obesity after tubular laparoscopic gastrectomy.

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Gallart-Aragón, Tania; Fernández-Lao, Carolina; Cózar-Ibañez, Antonio; Cantarero-Villanueva, Irene; Cambil-Martín, Jacobo; Jiménez Ríos, José Antonio; Arroyo-Morales, Manuel

2017-12-29

The objective of our study is to analyze the possible relationship between changes in glycemic profile and body composition parameters in morbid obesity patients after tubular laparoscopic gastrectomy. A prospective observational cohort study with 69 patients was performed. The variables analyzed were body weight, blood glucose, hemoglobin, glycosylated, high density lipoprotein, low density lipoprotein, triglycerides, and waist and hip circumference. An analysis of variance of repeated measurements (ANOVA) and a correlation analysis through the Pearson test were carried out. A significant reduction in weight (p<.001 after surgery) and in glycosylated hemoglobin (p<.036) and waist hip (p<.001) were found at 6 months after surgery. There was no significant difference in the rest of the variables studied. In correlation analysis, a significant positive correlation was found between the change in concentration of hemoglobin glycosylated and hip circumference (p=.047; r=0.237), the smaller the hip circumference, the lower the concentration of glycosylated hemoglobin. Tubular laparoscopic gastrectomy is an effective technique for the treatment of morbidly obese patients with type 2 diabetes mellitus. The reduction in the perimeter of hip is related to glycosylated hemoglobin reduction 6 months after intervention. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Improvement of Glycosylated Hemoglobin in Patients with Type 2 Diabetes Mellitus under Insulin Treatment by Reimbursement for Self-Monitoring of Blood Glucose

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Young Shin Song

2017-09-01

Full Text Available BackgroundIn Korea, the costs associated with self-monitoring of blood glucose (SMBG for patients with type 2 diabetes mellitus (T2DM under insulin treatment have been reimbursed since November 2015. We investigated whether this new reimbursement program for SMBG has improved the glycemic control in the beneficiaries of this policy.MethodsAmong all adult T2DM patients with ≥3 months of reimbursement (n=854, subjects without any changes in anti-hyperglycemic agents during the study period were selected. The improvement of glycosylated hemoglobin (HbA1c was defined as an absolute reduction in HbA1c ≥0.6% or an HbA1c level at follow-up <7%.ResultsHbA1c levels significantly decreased from 8.5%±1.3% to 8.2%±1.2% during the follow-up (P<0.001 in all the study subjects (n=409. Among them, 35.5% (n=145 showed a significant improvement in HbA1c. Subjects covered under the Medical Aid system showed a higher prevalence of improvement in HbA1c than those with medical insurance (52.2% vs. 33.3%, respectively, P=0.012. In the improvement group, the baseline HbA1c (P<0.001, fasting C-peptide (P=0.016, and daily dose of insulin/body weight (P=0.024 showed significant negative correlations with the degree of HbA1c change. Multivariate analysis showed that subjects in the Medical Aid system were about 2.5-fold more likely to improve in HbA1c compared to those with medical insurance (odds ratio, 2.459; 95% confidence interval, 1.138 to 5.314; P=0.022.ConclusionThe reimbursement for SMBG resulted in a significant improvement in HbA1c in T2DM subjects using insulin, which was more prominent in subjects with poor glucose control at baseline or covered under the Medical Aid system.

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients

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Castilho E.M.

2003-01-01

Full Text Available The position of the oxygen dissociation curve (ODC is modulated by 2,3-diphosphoglycerate (2,3-DPG. Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1 nondiabetic control individuals (N = 19; 2 insulin-dependent diabetes mellitus (IDDM patients (on insulin treatment (N = 19; 3 non-insulin-dependent diabetes mellitus (NIDDM patients using oral hypoglycemic agents and no insulin treatment (N = 22. The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%. In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control to 2.45 µmol/ml blood (IDDM. Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

The effects of 2,3-diphosphoglycerate, adenosine triphosphate, and glycosylated hemoglobin on the hemoglobin-oxygen affinity of diabetic patients.

Science.gov (United States)

Castilho, E M; Glass, M L; Manço, J C

2003-06-01

The position of the oxygen dissociation curve (ODC) is modulated by 2,3-diphosphoglycerate (2,3-DPG). Decreases in 2,3-DPG concentration within the red cell shift the curve to the left, whereas increases in concentration cause a shift to the right of the ODC. Some earlier studies on diabetic patients have reported that insulin treatment may reduce the red cell concentrations of 2,3-DPG, causing a shift of the ODC to the left, but the reports are contradictory. Three groups were compared in the present study: 1) nondiabetic control individuals (N = 19); 2) insulin-dependent diabetes mellitus (IDDM) patients (on insulin treatment) (N = 19); 3) non-insulin-dependent diabetes mellitus (NIDDM) patients using oral hypoglycemic agents and no insulin treatment (N = 22). The overall position of the ODC was the same for the three groups despite an increase of the glycosylated hemoglobin fraction that was expected to shift the ODC to the left in both groups of diabetic patients (HbA1c: control, 4.6%; IDDM, 10.5%; NIDDM, 9.0%). In IDDM patients, the effect of the glycosylated hemoglobin fraction on the position of the ODC appeared to be counterbalanced by small though statistically significant increases in 2,3-DPG concentration from 2.05 (control) to 2.45 mol/ml blood (IDDM). Though not statistically significant, an increase of 2,3-DPG also occurred in NIDDM patients, while red cell ATP levels were the same for all groups. The positions of the ODC were the same for control subjects, IDDM and NIDDM patients. Thus, the PO2 at 50% hemoglobin-oxygen saturation was 26.8, 28.2 and 28.5 mmHg for control, IDDM and NIDDM, respectively. In conclusion, our data question the idea of adverse side effects of insulin treatment on oxygen transport. In other words, the shift to the left reported by others to be caused by insulin treatment was not detected.

Effect of Cola acuminate on Blood Glucose and Glycosylated ...

African Journals Online (AJOL)

The levels of blood glucose and glycosylated haemoglobin (GHB) were studied in 42 Wistar rats divided into three groups; controls, group A and group B. Control rats consumed only feeds, group A consumed 0.04g of Cola acuminate, while group B consumed 0.08g of Cola acuminate mixed with their feeds daily for six ...

Cotransplantation of Mesenchymal Stem Cells and Immature Dendritic Cells Potentiates the Blood Glucose Control of Islet Allografts

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Guanghui Long

2017-01-01

Full Text Available Background. Transplantation of islets is a promising alternative to treat type 1 diabetes (T1D, but graft rejection is the major obstacle to its application in clinical practice. We evaluated the effects of mesenchymal stem cells (MSCs and immature dendritic cells (imDCs on islet transplantation in diabetic model. Methods. The streptozotocin T1D model was established in BABL/c mice. Rat islets were isolated and identified with dithizone (DTZ staining. MSCs and imDCs were isolated from bone marrow of syngenic mice. Islets, alone or along with MSCs and/or imDCs, were transplanted to the left kidney capsule of diabetic mice. The blood glucose levels and glycosylated hemoglobin levels after transplantation were monitored. Results. Cotransplantation significantly decreased blood glucose and glycosylated hemoglobin levels in the diabetes mice. Transplantation of 200 islets + 2 × 105 MSCs + 2 × 105 imDCs could not only restore normal blood glucose levels, but also significantly prolong graft survival for 12.6±3.48 days. Conclusions. Cotransplantation of allogenic islets with imDCs and/or MSCs can significantly promote graft survival, reverse hyperglycemia, and effectively control the glycosylated hemoglobin levels.

Glycosylation site-targeted PEGylation of glucose oxidase retains native enzymatic activity.

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Ritter, Dustin W; Roberts, Jason R; McShane, Michael J

2013-04-10

Targeted PEGylation of glucose oxidase at its glycosylation sites was investigated to determine the effect on enzymatic activity, as well as the bioconjugate's potential in an optical biosensing assay. Methoxy-poly(ethylene glycol)-hydrazide (4.5kDa) was covalently coupled to periodate-oxidized glycosylation sites of glucose oxidase from Aspergillus niger. The bioconjugate was characterized using gel electrophoresis, liquid chromatography, mass spectrometry, and dynamic light scattering. Gel electrophoresis data showed that the PEGylation protocol resulted in a drastic increase (ca. 100kDa) in the apparent molecular mass of the protein subunit, with complete conversion to the bioconjugate; liquid chromatography data corroborated this large increase in molecular size. Mass spectrometry data proved that the extent of PEGylation was six poly(ethylene glycol) chains per glucose oxidase dimer. Dynamic light scattering data indicated the absence of higher-order oligomers in the PEGylated GOx sample. To assess stability, enzymatic activity assays were performed in triplicate at multiple time points over the course of 29 days in the absence of glucose, as well as before and after exposure to 5% w/v glucose for 24h. At a confidence level of 95%, the bioconjugate's performance was statistically equivalent to native glucose oxidase in terms of activity retention over the 29 day time period, as well as following the 24h glucose exposure. Finally, the bioconjugate was entrapped within a poly(2-hydroxyethyl methacrylate) hydrogel containing an oxygen-sensitive phosphor, and the construct was shown to respond approximately linearly with a 220±73% signal change (n=4, 95% confidence interval) over the physiologically-relevant glucose range (i.e., 0-400mg/dL); to our knowledge, this represents the first demonstration of PEGylated glucose oxidase incorporated into an optical biosensing assay. Copyright © 2013 Elsevier Inc. All rights reserved.

Glucose monitoring as a guide to diabetes management. Critical subject review.

OpenAIRE

Koch, B.

1996-01-01

PURPOSE: To encourage a balanced approach to blood glucose monitoring in diabetes by a critical review of the history, power and cost of glucose testing. DATA SOURCES: The Cambridge Data Base was searched and was supplemented by a random review of other relevant sources, including textbooks, company pamphlets, and laboratory manuals. STUDY SELECTION: Keywords used were "glucosuria diagnosis," "blood glucose self-monitoring," "glycosylated hemoglobin," and "fructosamine" for the 10-year period...

Association between elevated pre-operative glycosylated hemoglobin and post-operative infections after non-emergent surgery.

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Blankush, Joseph M; Leitman, I Michael; Soleiman, Aron; Tran, Trung

2016-09-01

A chronic state of impaired glucose metabolism affects multiple components of the immune system, possibly leading to an increased incidence of post-operative infections. Such infections increase morbidity, length of stay, and overall cost. This study evaluates the correlation between elevated pre-operative glycosylated hemoglobin (HbA1c) and post-operative infections. Adult patients undergoing non-emergent procedures across all surgical subspecialties from January 2010 to July 2014 had a preoperative HbA1c measured as part of their routine pre-surgical assessment. 2200 patient charts (1100 operative infection (superficial surgical site infection, deep wound/surgical space abscess, pneumonia, and/or urinary tract infection as defined by Centers for Disease Control criteria) within 30 days of surgery. Patients with HbA1c infection rate (3.8% in the HbA1c infection. Elevated HbA1c was, however, predictive of significantly increased risk of post-operative infection when associated with increased age (≥81 years of age) or dirty wounds. The risk factors of post-operative infection are multiple and likely synergistic. While pre-operative HbA1c level is not independently associated with risk of post-operative infection, there are scenarios and patient subgroups where pre-operative HbA1c is useful in predicting an increased risk of infectious complications in the post-operative period.

The Association of Serum Cystatin C with Glycosylated Hemoglobin in Korean Adults

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Eun Hee Sim

2016-01-01

Full Text Available BackgroundCystatin C has been known to be associated not only with early renal impairment but also with the incidence of diabetic conditions (prediabetes plus diabetes. However, it is not clear whether cystatin C levels are associated with the prevalence of diabetic conditions in Asian populations. We evaluated this association using glycosylated hemoglobin (HbA1c levels as the definition of diabetes in Korean adults.MethodsWe analyzed data from 1,559 Korean adults (937 men and 622 women with available serum cystatin C and HbA1c values.ResultsThe serum cystatin C levels in subjects with prediabetes and diabetes were significantly increased (0.91±0.14 mg/L in prediabetes and 0.91±0.17 mg/L in diabetes vs. 0.88±0.13 mg/L in patients with normal glucose levels, P=0.001. At increasing cystatin C levels, the prevalence of subjects with prediabetes (30.2% vs. 14.6%, P<0.001 and those with diabetes (10.6% vs. 8.0%, P<0.001 significantly increased in the group with the highest cystatin C levels. The group with the highest cystatin C levels had a significantly increased odds ratio (OR for the presence of diabetic conditions compared to the group with the lowest values in total subjects (OR, 2.35; 95% confidence interval [CI], 1.54 to 3.58; P<0.001 and in women (OR, 4.13; 95% CI, 1.97 to 8.65; P<0.001, though there was no significant increase after adjusting for multiple variables.ConclusionsHigher levels of serum cystatin C are associated with an increased prevalence of diabetic conditions in Korean adults. Our findings may extend the positive association of cystatin C with diabetes incidence to an Asian population.

Effect of some high consumption spices on hemoglobin glycation.

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Naderi, G H; Dinani, Narges J; Asgary, S; Taher, M; Nikkhoo, N; Boshtam, M

2014-01-01

Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes.

The relationship between vegetables and fruits intake and glycosylated hemoglobin values, lipids profiles and nitrogen status in type II inactive diabetic patients

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Marjan Tabesh

2013-01-01

Conclusions : Intake of vegetables and fruits may reduce the glycosylated hemoglobin, therefore choosing the appropriate diet with high fruits and vegetables may help to develop antioxidant defense and reduce the HbA1C in diabetic patients but it did not have any impact on lipids profiles, BUN/creatinine and urine protein 24 h.

Elevated Hemoglobin A1C Levels Correlate with Blood Glucose Elevation in Diabetic Patients following Local Corticosteroid Injection in the Hand: A Prospective Study.

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Kim, Nayoung; Schroeder, Jake; Hoffler, C Edward; Matzon, Jonas L; Lutsky, Kevin F; Beredjiklian, Pedro K

2015-10-01

Diabetic patients develop hand conditions that are managed with local corticosteroid injections. Injections can result in a transient elevation in serum glucose in diabetic patients. Hemoglobin A1c is the accepted measure of long-term plasma glucose control in diabetics (levels ≥7 percent reflect poor blood glucose control). The purpose of this study was to assess the relationship between hemoglobin A1c levels and increased blood glucose levels after corticosteroid injections. Twenty-five diabetic patients were evaluated prospectively. One milliliter containing 10 mg of triamcinolone acetonide was used. The most recent hemoglobin A1c level and normal average blood glucose levels were obtained. Glucose levels were obtained from patient recall of their daily blood glucose self- monitoring on the day of the injection. Postinjection blood glucose levels were recorded until levels returned to preinjection baseline. Twenty patients (80 percent) had elevation of their blood glucose level from baseline. No patient had elevated blood glucose levels after 5 days. Patients with hemoglobin A1c levels greater than or equal to 7 percent had a higher blood glucose elevation and maintained this for longer than those who had a lower hemoglobin A1c level. Patients in the higher hemoglobin A1c group also had a higher number of hyperglycemic events. There was a strong or moderate correlation between hemoglobin A1c and elevated blood glucose levels during days 1 to 4. Patients with hemoglobin A1c levels greater than or equal to 7 percent have elevations in blood glucose that are higher and last longer than patients with lower levels. Hemoglobin A1c levels can be used to roughly predict the degree of blood glucose elevation after corticosteroid injections into the hands of diabetic patients.

The Correlation of Hemoglobin A1c to Blood Glucose

OpenAIRE

Sikaris, Ken

2009-01-01

The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this ...

Optimization of a colorimetric assay for glycosylated human serum albumin

International Nuclear Information System (INIS)

Bohney, J.P.; Feldhoff, R.C.

1986-01-01

The thiobarbituric acid (TBA) assay has been used for several years to quantitate the amount of glucose which has been non-enzymatically linked to hemoglobin and other proteins. The ketoamine-protein adduct is converted to 5-hydroxymethylfurfural (HMF) by mild hydrolysis with oxalic acid. Reaction of HMF with TBA yields a colored product which has an absorbance maximum at 443 nm. Several modifications of the original procedure has been published, but none permit the unambiguous quantitation of glycosylated human serum albumin (glc-HSA). Problems relate to reagent preparation and stability, the time and temperature of hydrolysis, the choice of standards, and background color corrections. The authors have found that maximum color yield occurs after hydrolysis in an autoclave for 2 h. This increases the sensitivity 3-fold and cuts the assay time in half relative to hydrolysis for 4.5 h at 100 0 C. A NaBH 4 reduction of a parallel protein sample must be performed to correct for variable background color associated with different sample sources and amounts. HMF can be used as a standard, however, corrections must be made for HMF degradation. Fructose is a better standard, but HMF formation from fructose is faster than formation from glc-HSA. This may result in an underestimate of percent glycosylation. The best standard appears to be glc-HSA prepared with [ 3 H]glucose. It appears that with proper controls and standards the TBA assay can be used to determine actual rather than relative percent glycosylation

Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation.

Science.gov (United States)

Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

2015-03-01

Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans

Cooperative roles of glucose and asparagine-linked glycosylation in T-type calcium channel expression

Czech Academy of Sciences Publication Activity Database

Lazniewska, Joanna; Rzhepetskyy, Yuriy; Zhang, F. X.; Zamponi, G. W.; Weiss, Norbert

2016-01-01

Roč. 468, 11/12 (2016), s. 1837-1851 ISSN 0031-6768 R&D Projects: GA ČR GA15-13556S; GA MŠk 7AMB15FR015 Institutional support: RVO:61388963 Keywords : calcium channel * T-type channel * Ca(v)3.2 * glucose * N-glycosylation * trafficking Subject RIV: CE - Biochemistry Impact factor: 3.156, year: 2016

Optimization of a colorimetric assay for glycosylated human serum albumin

Energy Technology Data Exchange (ETDEWEB)

Bohney, J.P.; Feldhoff, R.C.

1986-05-01

The thiobarbituric acid (TBA) assay has been used for several years to quantitate the amount of glucose which has been non-enzymatically linked to hemoglobin and other proteins. The ketoamine-protein adduct is converted to 5-hydroxymethylfurfural (HMF) by mild hydrolysis with oxalic acid. Reaction of HMF with TBA yields a colored product which has an absorbance maximum at 443 nm. Several modifications of the original procedure has been published, but none permit the unambiguous quantitation of glycosylated human serum albumin (glc-HSA). Problems relate to reagent preparation and stability, the time and temperature of hydrolysis, the choice of standards, and background color corrections. The authors have found that maximum color yield occurs after hydrolysis in an autoclave for 2 h. This increases the sensitivity 3-fold and cuts the assay time in half relative to hydrolysis for 4.5 h at 100/sup 0/C. A NaBH/sub 4/ reduction of a parallel protein sample must be performed to correct for variable background color associated with different sample sources and amounts. HMF can be used as a standard, however, corrections must be made for HMF degradation. Fructose is a better standard, but HMF formation from fructose is faster than formation from glc-HSA. This may result in an underestimate of percent glycosylation. The best standard appears to be glc-HSA prepared with (/sup 3/H)glucose. It appears that with proper controls and standards the TBA assay can be used to determine actual rather than relative percent glycosylation.

Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level.

Science.gov (United States)

Kim, Hyoung Joo; Kim, Young Geon; Park, Jin Soo; Ahn, Young Hwan; Ha, Kyoung Hwa; Kim, Dae Jung

2016-05-01

Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] - 149.6; R (2) = 0.54, p Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels.

Efficient synthesis of glycosylated phenazine natural products and analogs with DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors

DEFF Research Database (Denmark)

Laursen, Jane B.; Petersen, Lars; Jensen, K.J.

2003-01-01

Inspired by the occurrence and function of phenazines in natural products, new glycosylated analogs were designed and synthesized. DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors were used in an efficient and easily-handled glycosylation protocol compatible with combinatorial chemistry....... Benzoylated D-glucose, D-galactose and L-quinovose DISAL glycosyl donors were synthesized in high yields and used under mild conditions to glycosylate methyl saphenate and 2-hydroxyphenazine. The glycosides were screened for biological activity and one compound showed inhibitory activity towards topoisomerase...

Dynamic analysis of sexual organ weight and serum levels of glucose, glycosyl protein, testosterone in male rats with short-term diabetes

International Nuclear Information System (INIS)

Zou Donghui; Wang Zhongshan; Zhao Hui; Xu Zongge

2001-01-01

Objective: To study the effect of short-term diabetes on the changes of sexual organ weights and serum levels of testosterone in male rats. Methods: All rats were divided into control (C) and diabetes (D). Diabetes group was observed on 1 day, 3 days, 5 days, 7 days, 14 days after injection of streptozotocin. All rats were killed for measurement of serum levels of glucose, glycosyl protein, testosterone and weights of sexual organs (testis, epididymis, seminal vesicle and prostate). Results: The serum levels of glucose, glycosyl protein of diabetes group decreased significantly, compared with those of control group; the serum levels of T lowered remarkably compared with control levels after three days of injection of STZ. The weight of epididymis, seminal vesicle and prostate reduced remarkably, compared with control group. The weights of seminal vesicle, prostate negatively correlated with serum levels of glucose and glycosyl protein, and they positively correlated with serum levels of testosterone. Conclusion: The sexual organs (testis, epididymis, seminal vesicle and prostate) of male rats with short-term diabetes were damaged, and the changes of sexual organs closely related with the serum levels of testosterone besides irregular metabolism in diabetes

Algunos aspectos de actualidad sobre la hemoglobina glucosilada y sus aplicaciones Some updated features on glycosylated hemoglobin and its applications

Directory of Open Access Journals (Sweden)

Eduardo Álvarez Seijas

2009-12-01

Full Text Available La hemoglobina glucosilada es un examen que mide la cantidad de hemoglobina que se glucosila en la sangre, y brinda un buen estimado del control glucémico durante los últimos 3 meses en personas prediabéticas y diabéticas, por lo que habitualmente se utiliza en el monitoreo de esta enfermedad. Un comité de expertos en diabetes, formado en el año 2008, analizó la relación entre la exposición glucémica a largo plazo y las complicaciones crónicas de la diabetes mellitus, y recomienda esta prueba como una nueva herramienta diagnóstica para esta enfermedad. Por la importancia de este tema para la práctica médica, se realiza una descripción actualizada de los antecedentes, metodología, interpretaciones y usos de este examen.Glycosylated hemoglobin is an examination measuring the amount of hemoglobin glycosylated in blood and gave a good estimated of the glycemia control during the last three months in prediabetic and diabetic persons, thus, usually it is used in monitoring of this disease. An expert committee on diabetes created in 2008, analyzed the relationship between the long-term glycemia exposition and the chronic complications of diabetes mellitus, and recommended this type of test as a new diagnostic tool for this disease. Due to the significance of this topic for medical practice, an updated description of backgrounds, methodology, interpretation and uses of this examination is performed.

Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation

DEFF Research Database (Denmark)

Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian

2015-01-01

optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylationrelated product quality. In this work, different fed-batch processes with two chemically defined proprietary media......Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process...... and glutamine concentrations and uptake rates were positively correlated with intracellular UDP-Gal availability. All these findings are important for optimization of fed-batch culture for improving IgG production and directing glycosylation quality....

Glucose monitoring as a guide to diabetes management. Critical subject review.

Science.gov (United States)

Koch, B

1996-06-01

To encourage a balanced approach to blood glucose monitoring in diabetes by a critical review of the history, power and cost of glucose testing. The Cambridge Data Base was searched and was supplemented by a random review of other relevant sources, including textbooks, company pamphlets, and laboratory manuals. Keywords used were "glucosuria diagnosis," "blood glucose self-monitoring," "glycosylated hemoglobin," and "fructosamine" for the 10-year period ending 1992, restricted to English language and human. About 200 titles were retrieved and reviewed according to the author's judgment of relevance. "Snapshot tests" (venous and capillary blood glucose) and "memory tests" (urine glucose, glycated hemoglobin fractions and fructosamine) must be employed according to individual patients treatment goals. Day-to-day metabolic guidance is facilitated by capillary blood glucose testing for patients receiving insulin and by urine glucose testing for others. Capillary blood glucose testing is mandatory in cases of hypoglycemia unawareness (inability to sense hypoglycemia because of neuropathy) but is not a substitute for a knowledge of clinical hypoglycemia self-care. Criteria by reason (clinical judgement and cost effectiveness) must be separated from criteria by emotion (preoccupation with technology and marketing). No randomized studies show that any of these tests consistently improve clinical outcome. Optimal metabolic control and cost savings can be expected from a rational selection of tests.

[Non-enzymatic glycosylation of dietary protein in vitro].

Science.gov (United States)

Bednykh, B S; Evdokimov, I A; Sokolov, A I

2015-01-01

Non-enzymatic glycosylation of proteins, based on discovered by Mayarn reaction of carbohydrate aldehyde group with a free amino group of a protein molecule, is well known to experts in biochemistry of food industry. Generated brown solid in some cases give the product marketable qualities--crackling bread--in others conversely, worsen the product. The biological effects of far-advanced products of non-enzymatic protein glycosylation reaction have not been studied enough, although it was reported previously that they are not split by digestive enzymes and couldn't be absorbed by animals. The objective of this work was to compare the depth of glycosylation of different food proteins of animal and vegetable origin. The objects of the study were proteins of animal (casein, lactoglobulin, albumin) and vegetable (soy isolate, proteins of rice flour, buckwheat, oatmeal) origin, glucose and fructose were selected as glycosylation agents, exposure 15 days at 37 degrees C. Lactoglobulin was glycosylated to a lesser extent among the proteins of animal origin while protein of oatmeal was glycosylated in the least degree among vegetable proteins. Conversely, such proteins as casein and soya isolate protein bound rather large amounts of carbohydrates. Fructose binding with protein was generally higher than the binding of glucose. The only exception was a protein of oatmeal. When of glucose and fructose simultaneously presented in the incubation medium, glucose binding usually increased while binding of fructose, in contrast, reduced. According to the total amount of carbohydrate (mcg), which is able to attach a protein (mg) the studied food proteins located in the following order: albumin (38) > soy protein isolate (23) > casein (15,) > whey protein rice flour protein (6) > protein from buckwheat flour (3) > globulin (2) > protein of oatmeal (0.3). The results obtained are to be used to select the optimal combination of proteins and carbohydrates, in which the glycosylation

Association between effort-reward imbalance and glycosylated hemoglobin (HbA1c) among Chinese workers: results from SHISO study.

Science.gov (United States)

Xu, Weixian; Hang, Juan; Gao, Wei; Zhao, Yiming; Li, Weihong; Wang, Xinyu; Li, Zhaoping; Guo, Lijun

2012-02-01

The studies focusing on effort-reward imbalance and diabetes mellitus (DM)/glycosylated hemoglobin (HbA1c) are rare. We sought to examine the association between job stress evaluated by effort-reward imbalance (ERI) model and HbA1c in a Chinese population. We analyzed 680 subjects (465 men and 215 women) without DM or impaired glucose tolerance from the stress and health in Shenzhen workers (SHISO) study. Job stress was evaluated by effort-reward imbalance (ERI) model. HbA1c was measured by an automatic analyzer by means of high-performance liquid chromatography. The association between job stress and HbA1c was explored by variance analysis, partial correlations and multiple linear regression analysis. For women, effort, and ERI were positively associated with HbA1c (r = 0.22, p = 0,003; r = 0.21, p = 0.006, respectively), in contrast, reward was negatively associated with HbA1c (r = -0.17, p = 0.021), after controlling age, BMI and physical exercise in the partial correlation analysis; the similar results were confirmed in the multiple linear regression. No significant correlations between job stress and HbA1c were found for men. Effort and ERI are positively associated with HbA1c, and reward is inversely related to HbA1c among Chinese women. The association is not accounted for by age, BMI, and physical exercise. More efforts should be made to improve the job stress status of Chinese working women for the purpose of DM prevention.

[Effect of meal frequency and carbohydrate intake on the metabolic control of patients with type 2 diabetes mellitus].

Science.gov (United States)

Leiva, Tamara; Basfi-Fer, Karen; Rojas, Pamela; Carrasco, Fernando; Ruz O, Manuel

2016-10-01

Increasing meal frequency is commonly used in the clinical practice as part of the nutritional treatment of patients with type 2 Diabetes Mellitus (DM2), although its effect on metabolic control parameters is controversial. To evaluate the association of energy intake, meal frequency, and amount of carbohydrates with fasting plasma glucose and glycosylated hemoglobin in a group of patients with DM2 without insulin therapy. Dietary intake was evaluated in 60 subjects with DM2 through three-day food records. The meal frequency was estimated establishing the main meal times considering snacks. Meal frequency was 4.7 ± 1.1 times per day. There was a positive association between glycosylated and fasting blood glucose levels (p Meal frequency was associated with energy intake (p meal frequency, available carbohydrates and energy intake, body mass index and fasting plasma glucose were analyzed in a multiple linear regression model, fasting blood glucose was the variable that best predicted changes in glycosylated hemoglobin (45.5%). Meal frequency had no association with glycosylated hemoglobin. Meal frequency showed no association with metabolic control parameters in DM2 patients.

The Association of Increased Total Glycosylated Hemoglobin Levels with Delayed Age at Menarche in Young Women with Type 1 Diabetes

Science.gov (United States)

Danielson, Kirstie K.; Palta, Mari; Allen, Catherine; D’Alessio, Donn J.

2005-01-01

Context: Delayed menarche is associated with subsequent reproductive and skeletal complications. Previous research has found delayed growth and pubertal maturation with type 1 diabetes and with poor glycemic control. The effect of diabetes management on menarche is important to clarify because tighter control might prevent these complications. Objective: To investigate age at menarche in young women with type 1 diabetes, and examine the effect of diabetes management (e.g. total glycosylated hemoglobin (GHb) level, number of blood glucose checks, insulin therapy intensity, insulin dose) on age at menarche in those diagnosed before menarche. Design: The Wisconsin Diabetes Registry Project is a follow-up study of a type 1 diabetes population-based incident cohort initially enrolled 1987 – 1992. Setting: Twenty-eight counties in south-central Wisconsin. Patients or Other Participants: Recruited through referrals, self-report, and hospital/clinic ascertainment. Individuals with newly diagnosed type 1 diabetes, <30 years old, were invited to participate. Of 288 young women enrolled, 188 reported menarche by 2002; 105 were diagnosed before menarche. Interventions: Not applicable. Main Outcome Measure: Age at menarche. Results: Mean age at menarche was 12.78 years, compared to 12.54 years in the United States (p = 0.01). Ages at menarche and diagnosis were not associated. For those diagnosed before menarche, age at menarche was delayed 1.3 months with each one percent increase in mean total GHb level in the three years prior to menarche. Conclusions: Age at menarche was moderately delayed in young women with type 1 diabetes. Delayed menarche could potentially be minimized with improved GHb levels. PMID:16204372

Oral health and glycosylated hemoglobin among type 1 diabetes children in South India

Directory of Open Access Journals (Sweden)

K Vidya

2018-01-01

Full Text Available Background: The study was an attempt to evaluate the relationship between oral health status and the level of glycemic control in type 1 diabetes patients. Methods: The study was carried out in 87 children with type 1 diabetes, aged 8–16 years, attending a diabetes specialty hospital. The oral health of these patients was measured using the WHO 1997 Oral Health Survey criteria for diagnosis of dental caries, gingival index, and plaque index. Samples were then divided into two groups as controlled (≤6.99% glycosylated hemoglobin [HbA1c] and uncontrolled (≥7% HbA1c diabetes as per the guidelines for glycemic control in diabetics given by the American Diabetes Association. The oral health between the groups was compared. Results: Data were statistically analyzed using student t-test. Results showed a significant difference in decayed, missing, and filled surface component (P = 0.043 and gingival index scores (P< 0.001 in the permanent dentition between controlled and uncontrolled groups but not in case of the primary dentition. Conclusions: The data findings suggest that metabolic control had an impact on caries prevalence and gingival health of these patients, in case of permanent dentition. As the glycemic control became poorer, the caries prevalence and gingival inflammation increased. When primary dentition was taken into consideration, the correlation was not significant.

Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes.

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Latha, M; Pari, L

2004-04-01

The effects of an aqueous extract of the plant Scoparia dulcis (200 mg/kg) on the polyol pathway and lipid peroxidation were examined in the liver of streptozotocin adult diabetic male albino Wistar rats. The diabetic control rats (N = 6) presented a significant increase in blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS) and hydroperoxides, and a significant decrease in plasma insulin and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) compared to normal rats (N = 6). Scoparia dulcis plant extract (SPEt, 200 mg kg-1 day-1) and glibenclamide (600 microg kg-1 day-1), a reference drug, were administered by gavage for 6 weeks to diabetic rats (N = 6 for each group) and significantly reduced blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin, TBARS, and hydroperoxides, and significantly increased plasma insulin, GPx, GST and GSH activities in liver. The effect of the SPEt was compared with that of glibenclamide. The effect of the extract may have been due to the decreased influx of glucose into the polyol pathway leading to increased activities of antioxidant enzymes and plasma insulin and decreased activity of sorbitol dehydrogenase. These results indicate that the SPEt was effective in attenuating hyperglycemia in rats and their susceptibility to oxygen free radicals.

Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes

Directory of Open Access Journals (Sweden)

M. Latha

2004-04-01

Full Text Available The effects of an aqueous extract of the plant Scoparia dulcis (200 mg/kg on the polyol pathway and lipid peroxidation were examined in the liver of streptozotocin adult diabetic male albino Wistar rats. The diabetic control rats (N = 6 presented a significant increase in blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin and lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS and hydroperoxides, and a significant decrease in plasma insulin and antioxidant enzymes such as glutathione peroxidase (GPx, glutathione-S-transferase (GST and reduced glutathione (GSH compared to normal rats (N = 6. Scoparia dulcis plant extract (SPEt, 200 mg kg-1 day-1 and glibenclamide (600 µg kg-1 day-1, a reference drug, were administered by gavage for 6 weeks to diabetic rats (N = 6 for each group and significantly reduced blood glucose, sorbitol dehydrogenase, glycosylated hemoglobin, TBARS, and hydroperoxides, and significantly increased plasma insulin, GPx, GST and GSH activities in liver. The effect of the SPEt was compared with that of glibenclamide. The effect of the extract may have been due to the decreased influx of glucose into the polyol pathway leading to increased activities of antioxidant enzymes and plasma insulin and decreased activity of sorbitol dehydrogenase. These results indicate that the SPEt was effective in attenuating hyperglycemia in rats and their susceptibility to oxygen free radicals.

Defectively N-glycosylated and non-O-glycosylated aminopeptidase N (CD13) is normally expressed at the cell surface and has full enzymatic activity

DEFF Research Database (Denmark)

Norén, K; Hansen, Gert Helge; Clausen, H

1997-01-01

In order to study the effects of the absence of O-glycosylation and modifications of N-glycosylation on a class II membrane protein, pig and human aminopeptidase N (CD13) were stably expressed in the ldl(D) cell line. This cell line carries a UDP-Gal/UDP-GalNAc-epimerase deficiency which blocks...... the conversion of glucose into galactose derivatives. Thus it is possible in the ldl(D) cell line to selectively block O-glycosylation by the omission of N-acetylgalactoseamine from the culture medium and to alter N-glycosylation by the omission of galactose. In this way selectively altered glycosylated forms...

HEMOGLOBINA GLICOSILADA O HEMOGLOBINA GLICADA, ¿CUÁL DE LAS DOS? | GLYCOSILATED HEMOGLOBIN OR GLYCATED HEMOGLOBIN, WHICH OF THE TWO?

Directory of Open Access Journals (Sweden)

Mariela Bracho-Nava

2015-11-01

, according to the International Federation of Clinical Chemistry (IFCC, as a generic term referring to a group of substances that are formed from biochemical reactions between hemoglobin A (HbA and some reducing sugars present in the bloodstream, glucose being the most abundant of them. This reaction is known as the Maillard reaction, which is based on a non-enzimatic glycosylation, or more correctly called, in a glycation. Custom, ignorance or confusion among both chemical processes has led to use the term glycosylated hemoglobin instead of glycated hemoglobin. This article provides a review of the process of formation of hemoglobin A1c, defining the reaction of glycosylation and the protein glycation, the chemical species that favor the glycation, the characteristics of the process of glycation of hemoglobin, stages in which it occurs and the effects related to the glycation of proteins in human beings, to finally conclude with a passage of designations which has received the HbA1c to the present; all with the aim of clarifying and giving property to the use of the term glycated hemoglobin.

Associations between long-term exposure to air pollution, glycosylated hemoglobin and diabetes.

Science.gov (United States)

Honda, Trenton; Pun, Vivian C; Manjourides, Justin; Suh, Helen

2017-10-01

Air pollution exposures have been shown to adversely impact health through a number of biological pathways associated with glucose metabolism. However, few studies have evaluated the associations between air pollution and glycosylated hemoglobin (HbA1c) levels. Further, no studies have evaluated these associations in US populations or investigated whether associations differ in diabetic as compared to non-diabetic populations. To address this knowledge gap, we investigated the associations between airborne fine particulate matter (PM 2.5 ) and nitrogen dioxide (NO 2 ) and HbA1c levels in both diabetic and non-diabetic older Americans. We also examined the impact of PM 2.5 and NO 2 on prevalent diabetes mellitus (DM) in this cohort. We used multilevel logistic and linear regression models to evaluate the association between long-term average air pollutant levels and prevalence of DM and HbA1c levels, respectively, among 4121 older (57+ years) Americans enrolled in the National Social Life, Health, and Aging Project between 2005 and 2011. All models adjusted for age, sex, body mass index, smoking status, race, household income, education level, neighborhood socioeconomic status, geographic region, urbanicity and diabetic medication use. We estimated participant-specific exposures to PM 2.5 on a six-kilometer grid covering the conterminous U.S. using spatio-temporal models, and to NO 2 using nearest measurements from the Environmental Protection Agency's Air Quality System. HbA1c levels were measured for participants in each of two data collection waves from dried blood spots and log-transformed prior to analysis. Participants were considered diabetic if they had HbA1c values≥6.5% or reported taking diabetic medication. The prevalence of diabetes at study entry was 22.2% (n=916) and the mean HbA1c was 6.0±1.1%. Mean one-year moving average PM 2.5 and NO 2 exposures were 10.4±3.0μg/m 3 and 13.1±7.0 ppb, respectively. An inter-quartile range (IQR, 3.9μg/m 3

Hemoglobin A1c, fasting plasma glucose, and 2-hour plasma glucose distributions in U.S. population subgroups: NHANES 2005-2010.

Science.gov (United States)

Menke, Andy; Rust, Keith F; Savage, Peter J; Cowie, Catherine C

2014-02-01

Although mean concentrations of hemoglobin A1c (A1C), fasting plasma glucose, and 2-hour plasma glucose differ by demographics, it is unclear what other characteristics of the distributions may differ, such as the amount of asymmetry of the distribution (skewness) and shift left or right compared with another distribution (shift). Using kernel density estimation, we created smoothed plots of the distributions of fasting plasma glucose (N = 7250), 2-hour plasma glucose (N = 5851), and A1C (N = 16,209) by age, race-ethnicity, and sex in the 2005-2010 National Health and Nutrition Examination Survey, a nationally representative sample of U.S. adults including people with and without diabetes. We tested differences in distributions using cumulative logistic regression. The distributions were generally unimodal and right-skewed. All distributions were shifted higher and more right-skewed for older age groups (P Mexican-Americans (P = .01), whereas the distribution of A1C was shifted higher for non-Hispanic blacks (P rights reserved.

Halide-mediated regioselective 6-O-glycosylation of unprotected hexopyranosides with perbenzylated glycosyl bromide donors

DEFF Research Database (Denmark)

Niedbal, Dominika Alina; Madsen, Robert

2016-01-01

The regio- and stereoselective glycosylation at the 6-position in 2,3,4,6-unprotected hexopyranosides has been investigated with dibutyltin oxide as the directing agent. Perbenzylated hexopyranosyl bromides were employed as the donors and the glycosylations were promoted by tetrabutylammonium...... bromide. The couplings were completely selective for both glucose and galactose donors and acceptors as long as the stannylene acetal of the acceptor was soluble in dichloromethane. This gave rise to a number of 1,2-cis-linked disaccharides in reasonable yields. Mannose donors and acceptors, on the other...

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

Science.gov (United States)

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

Does Physical Activity Mediate the Associations Between Local-Area Descriptive Norms, Built Environment Walkability, and Glycosylated Hemoglobin?

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Carroll, Suzanne J; Niyonsenga, Theo; Coffee, Neil T; Taylor, Anne W; Daniel, Mark

2017-08-23

Associations between local-area residential features and glycosylated hemoglobin (HbA 1c ) may be mediated by individual-level health behaviors. Such indirect effects have rarely been tested. This study assessed whether individual-level self-reported physical activity mediated the influence of local-area descriptive norms and objectively expressed walkability on 10-year change in HbA 1c . HbA 1c was assessed three times for adults in a 10-year population-based biomedical cohort ( n = 4056). Local-area norms specific to each participant were calculated, aggregating responses from a separate statewide surveillance survey for 1600 m road-network buffers centered on participant addresses (local prevalence of overweight/obesity (body mass index ≥25 kg/m²) and physical inactivity (Walkability was directly and indirectly protective of worsening HbA 1c . Local-area descriptive norms and walkability influence cardiometabolic risk trajectory through individual-level physical activity. Efforts to reduce population cardiometabolic risk should consider the extent of local-area unhealthful behavioral norms and walkability in tailoring strategies to improve physical activity.

Efficacy of Tribulus Terrestris Extract on the Serum Glucose and Lipids of Women with Diabetes Mellitus.

Science.gov (United States)

Samani, Nasrin Babadai; Jokar, Azam; Soveid, Mahmood; Heydari, Mojtaba; Mosavat, Seyed Hamdollah

2016-05-01

Considering folkloric use of Tribulus terrestris (T. terrestris) in diabetes and proven anti-hyperglycemic and anti-hyperlipidemic effects of T. terrestris in animal studies, we aimed to evaluate the efficacy of the hydro alcoholic extract of T. terrestris on the serum glucose and lipid profile of women with diabetes mellitus. Ninety-eight diabetic women were randomly allocated to receive the T. terrestris (1000 mg/day) or placebo for three months. The patients were evaluated in terms of the fasting blood glucose, 2-hour postprandial glucose, glycosylated hemoglobin and lipid profile. T. terrestris showed a significant blood glucose lowering effect in diabetic women compared to placebo (Pterrestris group was significantly reduced compared with placebo, while no significant effect was observed in the triglyceride and high-density lipoprotein levels. This study showed preliminary promising hypoglycemic effect of T. terrestris in diabetic women.

Nonenzymatic glycosylation of bovine myelin basic protein

International Nuclear Information System (INIS)

Hitz, J.B.

1987-01-01

In the CNS myelin sheath the nonenzymatic glycosylation reaction (at the early stage of the Amadori product) occurs only with the myelin basic protein and not with the other myelin proteins. This was observed in isolated bovine myelin by in vitro incubation with [ 14 C]-galactose and [ 14 C]-glucose. The respective in-vitro incorporation rates for purified bovine myelin basic protein with D-galactose, D-glucose and D-mannose were 7.2, 2.4 and 2.4 mmoles/mole myelin basic protein per day at 37 0 C. A more rapid, HPLC method was devised and characterized to specifically analyze for the Amadori product. The HPLC method was correlated to the [ 14 C]-sugar incorporation method for myelin basic protein under a set of standard reaction conditions using [ 14 C]-glucose and [ 14 C]-mannose with HPLC values at 1/6 and 1/5 of the [ 14 C]-sugar incorporation method. A novel myelin basic protein purification step has been developed that yields a relativity proteolytic free preparation that is easy to work with, being totally soluble at a neutral pH. Nine new spots appear for a trypsinized glycosylated MBP in the paper peptide map of which eight correspond to positions of the [ 3 H]-labeled Amadori product in affinity isolated peptides. These studies provide a general characterization of and a structural basis for investigations on nonenzymatically glycosylated MBP as well as identifying MBP as the only nonenzymatically glycosylated protein in the CNS myelin sheath which may accumulate during aging, diabetes, and demyelinating diseases in general

fasting blood glucose and glycosylated haemoglobin levels

African Journals Online (AJOL)

Prince Acheampong

(HbA1c) levels of diabetes mellitus patients as an index of glycaemic control. It was a prospective case- finding study using laboratory and general practice records. ... range of glycosylated haemoglobins, and the cut-off values for some clinical .... quality of glycaemic control by glycated haemoglobin in out-patient diabetic ...

Association of glycated hemoglobin with carotid intimal medial thickness in Asian Indians with normal glucose tolerance.

Science.gov (United States)

Venkataraman, Vijayachandrika; Amutha, Anandakumar; Anbalagan, Viknesh Prabu; Deepa, Mohan; Anjana, Ranjit Mohan; Unnikrishnan, Ranjit; Vamsi, Mamilla; Mohan, Viswananthan

2012-01-01

To assess the association of glycated hemoglobin (HbA1c) levels with carotid intimal medial thickness (CIMT) in Asian Indians with normal glucose tolerance (NGT). Subjects with NGT were recruited from the Chennai Urban Rural Epidemiology Study carried out on a representative population of Chennai, South India. All subjects had fasting plasma glucose right common carotid artery using high-resolution B-mode ultrasonography. The study group included 1383 NGT subjects, of whom 760 (54.9%) were women. The mean CIMT value in the 1st quartile of HbA1c (5.8) (prights reserved.

The effect of impaired glucose metabolism on weight loss in multidisciplinary childhood obesity treatment

DEFF Research Database (Denmark)

Kloppenborg, Julie T; Gamborg, Michael; Fonvig, Cilius E

2017-01-01

and adolescents from the Children's Obesity Clinic, Holbaek, Denmark. Anthropometrics, pubertal development, socioeconomic status (SES), and fasting concentrations of plasma glucose, serum insulin, serum C-peptide, and whole blood glycosylated hemoglobin (HbA1c) were collected at treatment entry and at follow......OBJECTIVE: To investigate whether children and adolescents exhibiting an impaired glucose metabolism are more obese at treatment entry and less likely to reduce their degree of obesity during treatment. METHODS: The present study is a longitudinal observational study, including children...... mass index (BMI) z-score 2.94 (range 1.34-5.54) were included. The mean BMI z-score reduction was 0.31 (±0.46) after 13 months (range 6-18) of treatment. At treatment entry, patients with impaired estimates of glucose metabolism were more obese than normoglycemic patients. Baseline concentration of C...

Efficacy of Tribulus Terrestris Extract on the Serum Glucose and Lipids of Women with Diabetes Mellitus

Science.gov (United States)

Samani, Nasrin Babadai; Jokar, Azam; Soveid, Mahmood; Heydari, Mojtaba; Mosavat, Seyed Hamdollah

2016-01-01

Background: Considering folkloric use of Tribulus terrestris (T. terrestris) in diabetes and proven anti-hyperglycemic and anti-hyperlipidemic effects of T. terrestris in animal studies, we aimed to evaluate the efficacy of the hydro alcoholic extract of T. terrestris on the serum glucose and lipid profile of women with diabetes mellitus. Methods: Ninety-eight diabetic women were randomly allocated to receive the T. terrestris (1000 mg/day) or placebo for three months. The patients were evaluated in terms of the fasting blood glucose, 2-hour postprandial glucose, glycosylated hemoglobin and lipid profile. Results: T. terrestris showed a significant blood glucose lowering effect in diabetic women compared to placebo (Pterrestris group was significantly reduced compared with placebo, while no significant effect was observed in the triglyceride and high-density lipoprotein levels. Conclusion: This study showed preliminary promising hypoglycemic effect of T. terrestris in diabetic women. PMID:27840471

Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch*

Science.gov (United States)

Harvey, Beth M.; Rana, Nadia A.; Moss, Hillary; Leonardi, Jessica; Jafar-Nejad, Hamed; Haltiwanger, Robert S.

2016-01-01

Glycosylation of the Notch receptor is essential for its activity and serves as an important modulator of signaling. Three major forms of O-glycosylation are predicted to occur at consensus sites within the epidermal growth factor-like repeats in the extracellular domain of the receptor: O-fucosylation, O-glucosylation, and O-GlcNAcylation. We have performed comprehensive mass spectral analyses of these three types of O-glycosylation on Drosophila Notch produced in S2 cells and identified peptides containing all 22 predicted O-fucose sites, all 18 predicted O-glucose sites, and all 18 putative O-GlcNAc sites. Using semiquantitative mass spectral methods, we have evaluated the occupancy and relative amounts of glycans at each site. The majority of the O-fucose sites were modified to high stoichiometries. Upon expression of the β3-N-acetylglucosaminyltransferase Fringe with Notch, we observed varying degrees of elongation beyond O-fucose monosaccharide, indicating that Fringe preferentially modifies certain sites more than others. Rumi modified O-glucose sites to high stoichiometries, although elongation of the O-glucose was site-specific. Although the current putative consensus sequence for O-GlcNAcylation predicts 18 O-GlcNAc sites on Notch, we only observed apparent O-GlcNAc modification at five sites. In addition, we performed mass spectral analysis on endogenous Notch purified from Drosophila embryos and found that the glycosylation states were similar to those found on Notch from S2 cells. These data provide foundational information for future studies investigating the mechanisms of how O-glycosylation regulates Notch activity. PMID:27268051

Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

Science.gov (United States)

Zhang, Bingjie; Wang, Jing; Shen, Shanmei; Liu, Jiayi; Sun, Jie; Ye, Xiao

2018-01-01

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

A comparative study of fasting, postprandial blood glucose and glycated hemoglobin for diagnosing diabetes mellitus in staff members of MMIMSR, Mullana, Ambala

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Qazi Najeeb

2015-01-01

Full Text Available Introduction: For decades, the diagnosis of diabetes mellitus was based on blood glucose criteria, either the fasting blood glucose (FBG or a 2-h value in the 75-g oral glucose tolerance test. In 2009, an International Expert Committee that included representatives of the American Diabetes Association (ADA, International Diabetes Federation and European Association for the Study of Diabetes recommended the use of the HbA1c test to diagnose diabetes with a threshold of ≥6.5% and this criterion was finally adopted by ADA in 2010. Hence, the study was undertaken to evaluate the predictive efficacy of glycated hemoglobin as a diagnostic tool for diabetes mellitus and to identify individuals at risk of developing diabetes mellitus using Indian Diabetes Risk Score (IDRS. Materials and Methods: This cross-sectional study was conducted on the staff members of the Maharishi Markandeshwar Institute of Medical Science and Research, Mullana, Ambala, Haryana, India. Out of the total 800 staff members, 200 staff members were included in the study (88 faculty members, 37 staff nurses, 12 laboratory technicians, 25 clerical staff, 38 class IV selected by systemic random sampling. Every fifth member on the list was included in the sample. After obtaining the data, it was coded and analyzed using multivariate logistic regression analysis. Receiver operating characteristics curve analysis was used to predict the sensitivity, specificity, positivity, negativity and overall accuracy of a diagnostic test. A two-tailed test P < 0.05 was considered as statistically significant. Data was analyzed using SPSS 20 (IBM, Chicago, USA. Results: Out of 200 subjects, 19.5% were labeled diabetic using FBG, 23% by postprandial blood glucose (PPBG and 38.5% by using glycated hemoglobin according to ADA guidelines. A total of 62% had high-risk score out of which majority belonged to group-I (faculty followed by group-II (nursing staff and group-IV (clerical staff. With the

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin

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Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

2016-01-01

Abstract This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels. A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index. After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10–1.62), 1.46 (1.08–1.98), and 1.47 (1.12–1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24–3.51; HR = 4.00, 95% CI = 2.03–7.90; and HR = 2.05, 95% CI = 1.29–3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48–3.02; and HR = 1.35, 95% CI = 1.10–1.65, respectively). Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping HOMA-IR index. PMID:26844520

[Diagnostic agreement between two glycosylated a1b hemoglobin methods in Primary Care].

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Villar-del-Campo, M C; Rodríguez-Caravaca, G; Gil-Yonte, P; Cidoncha-Calderón, E; García-Cruces Méndez, J; Donnay-Pérez, S

2014-01-01

Several methods are available for measuring glycosylated A1c hemoglobin (HbA1c), all rapid methods for point of care use in a clinical or laboratory setting. This study attempts to compare the diagnostic agreement between two methods for detection of HbA1c. A descriptive cross-sectional study of diagnostic agreement was carried out in the Los Carmenes Health Centre. Two groups of patients -with and without type 2 diabetes- were consecutively included. A method for point-of-care use in a Primary Care Clinic setting (DCA(TM) Systems Siemens(®)) was compared with a laboratory test (chromatographic analysis). An analysis was made of the mean concentration of HbA1c, the agreement between methods, using the intra-class correlation coefficient (CCLA1) and the Bland-Altman method. A total of 102 patients were included, 62 diabetic (60.8%) and 40 non-diabetic (39.2%). The overall mean HbA1c was 6.46% (SD=0.88) in the analysis using capillary blood in the clinic with the DCA™ system, and 6.44% (SD=0.86) using the laboratory test (P>.05). The degree of agreement between the two tests was 0.975 (95% CI: 0.963-0.983). The mean of the differences between the results of the two assessed tests was 0.024 (SD=0.27). The percentage of points outside the limits of optimal agreement, as defined in the Bland-Altman graph, was 2.5%. Diagnostic agreement between a method for point-of-care use in a Primary Health Care Clinic and a laboratory test was very high. Detection at the point-of-care allows a quick and simple assessment of HbA1c. Copyright © 2013 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

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Kandasamy, Neelamegam; Ashokkumar, Natarajan

2014-09-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Red cell distribution width is associated with hemoglobin A1C elevation, but not glucose elevation.

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Bao, Xue; Wan, Min; Gu, Yeqing; Song, Yanqi; Zhang, Qing; Liu, Li; Meng, Ge; Wu, Hongmei; Xia, Yang; Shi, HongBin; Su, Qian; Fang, Liyun; Yang, Huijun; Yu, Fei; Sun, Shaomei; Wang, Xing; Zhou, Ming; Jia, Qiyu; Song, Kun; Wang, Guolin; Yu, Ming; Niu, Kaijun

2017-10-01

To investigate the association between red cell distribution width (RDW) and elevation of glucose/glycated hemoglobin (HbA1c). An analysis was conducted using data from a prospective cohort study of adults. People without prediabetes or diabetes (n=7,795) were followed for a mean of 2.90years (range: 1-7years, 95% confidence interval: 2.86-2.94years). Glucose elevation is defined as fasting glucose levels exceeding 5.6mmol/l, or 2-hour glucose values in the oral glucose tolerance test exceeding 7.8mmol/l. HbA1c elevation is defined as a HbA1c value exceeding a normal limit of 39mmol/mol (5.7%). Adjusted Cox proportional hazards regression models were used to assess the association between RDW quartiles and elevation of HbA1c/glucose. The multiple-adjusted hazard ratios (95% confidence interval) of HbA1c elevation for increased quartiles of RDW were 1.00 (reference), 1.08 (0.89, 1.30), 1.28 (1.07, 1.54), and 1.54 (1.29, 1.85) (P for trend<0.0001). However, no significant association was observed between RDW and blood glucose (fasting and postprandial). Elevated RDW is independently related to future HbA1c elevation, but not to glucose elevation. This suggests that RDW may associate with HbA1c through a non-glycemic way, which should be taken into consideration when using HbA1c as a diagnostic criterion of prediabetes or diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Led Astray by Hemoglobin A1c

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Jean Chen MD

2016-01-01

Full Text Available Hemoglobin A1c (A1c is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

Impaired fasting glucose and the metabolic profile in Danish children and adolescents with normal weight, overweight, or obesity

DEFF Research Database (Denmark)

Kloppenborg, Julie T; Fonvig, Cilius E; Nielsen, Tenna R H

2017-01-01

OBJECTIVE: Whether the definitions of impaired fasting glucose (IFG) from the American Diabetes Association (ADA) and the World Health Organization (WHO) differentially impact estimates of the metabolic profile and IFG-related comorbidities in Danish children and adolescents is unknown. METHODS......: Two thousand one hundred and fifty four (979 boys) children and adolescents with overweight or obesity (median age 12 years) and 1824 (728 boys) children with normal weight (median age 12 years) from The Danish Childhood Obesity Biobank were studied. Anthropometrics, blood pressure, puberty......, and fasting concentrations of glucose, insulin, glycosylated hemoglobin (HbA1c), and lipids were measured. RESULTS: About 14.1% of participants with overweight or obesity exhibited IFG according to the ADA and 3.5% according to the WHO definition. Among individuals with normal weight, the corresponding...

Keeping Track of Your Blood Sugar

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... glycosylated hemoglobin test (also known as the hemoglobin A1c or HbA1c test) will tell you how you've been ... that has glucose attached to it is called HbA1c. In general, the lower your HbA1c, the better ...

Optical detection of glucose and glycated hemoglobin using etched fiber Bragg gratings coated with functionalized reduced graphene oxide.

Science.gov (United States)

Sridevi, S; Vasu, K S; Sampath, S; Asokan, S; Sood, A K

2016-07-01

An enhanced optical detection of D-glucose and glycated hemoglobin (HbA1c ) has been established in this study using etched fiber Bragg gratings (eFBG) coated with aminophenylboronic acid (APBA)-functionalized reduced graphene oxide (RGO). The read out, namely the shift in Bragg wavelength (ΔλB ) is highly sensitive to changes that occur due to the adsorption of glucose (or HbA1c ) molecules on the eFBG sensor coated with APBA-RGO complex through a five-membered cyclic ester bond formation between glucose and APBA molecules. A limit of detection of 1 nM is achieved with a linear range of detection from 1 nM to 10 mM in the case of D-glucose detection experiments. For HbA1c , a linear range of detection varying from 86 nM to 0.23 mM is achieved. The observation of only 4 pm (picometer) change in ΔλB even for the 10 mM lactose solution confirms the specificity of the APBA-RGO complex coated eFBG sensors to glucose molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

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Bingjie Zhang

2018-01-01

Full Text Available Women with polycystic ovary syndrome (PCOS show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR and Matsuda insulin sensitivity index (ISIM; β-cell function was assessed by disposition index (DI. We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001. Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434, even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c, plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

Higher glucose levels associated with lower memory and reduced hippocampal microstructure.

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Kerti, Lucia; Witte, A Veronica; Winkler, Angela; Grittner, Ulrike; Rujescu, Dan; Flöel, Agnes

2013-11-12

For this cross-sectional study, we aimed to elucidate whether higher glycosylated hemoglobin (HbA1c) and glucose levels exert a negative impact on memory performance and hippocampal volume and microstructure in a cohort of healthy, older, nondiabetic individuals without dementia. In 141 individuals (72 women, mean age 63.1 years ± 6.9 SD), memory was tested using the Rey Auditory Verbal Learning Test. Peripheral levels of fasting HbA1c, glucose, and insulin and 3-tesla MRI scans were acquired to assess hippocampal volume and microstructure, as indicated by gray matter barrier density. Linear regression and simple mediation models were calculated to examine associations among memory, glucose metabolism, and hippocampal parameters. Lower HbA1c and glucose levels were significantly associated with better scores in delayed recall, learning ability, and memory consolidation. In multiple regression models, HbA1c remained strongly associated with memory performance. Moreover, mediation analyses indicated that beneficial effects of lower HbA1c on memory are in part mediated by hippocampal volume and microstructure. Our results indicate that even in the absence of manifest type 2 diabetes mellitus or impaired glucose tolerance, chronically higher blood glucose levels exert a negative influence on cognition, possibly mediated by structural changes in learning-relevant brain areas. Therefore, strategies aimed at lowering glucose levels even in the normal range may beneficially influence cognition in the older population, a hypothesis to be examined in future interventional trials.

Relationship of Glucose Variability With Glycated Hemoglobin and Daily Mean Glucose: A Post Hoc Analysis of Data From 5 Phase 3 Studies.

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Luo, Junxiang; Qu, Yongming; Zhang, Qianyi; Chang, Annette M; Jacober, Scott J

2018-03-01

The association of glucose variability (GV) with other glycemic measures is emerging as a topic of interest. The aim of this analysis is to study the correlation between GV and measures of glycemic control, such as glycated hemoglobin (HbA1c) and daily mean glucose (DMG). Data from 5 phase 3 trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes (T1D). A generalized boosted model was used post hoc to assess the relationship of the following variables with glycemic control parameters (HbA1c and DMG): within-day GV, between-day GV (calculated using self-monitored blood glucose and fasting blood glucose [FBG]), hypoglycemia rate, and certain baseline characteristics. Within-day GV (calculated using standard deviation [SD]) was found to have a significant influence on endpoints HbA1c and DMG in all 3 patient groups. Between-day GV from FBG (calculated using SD), within-day GV (calculated using coefficient of variation), and hypoglycemia rate were found to significantly influence the endpoint HbA1c in the T2D basal-only group. Lower within-day GV was significantly associated with improvement in DMG and HbA1c. This finding suggests that GV could be a marker in the early phases of new antihyperglycemic therapy development for predicting clinical outcomes in terms of HbA1c and DMG.

Validation and modification of dried blood spot-based glycosylated hemoglobin assay for the longitudinal aging study in India.

Science.gov (United States)

Hu, Peifeng; Edenfield, Michael; Potter, Alan; Kale, Varsha; Risbud, Arun; Williams, Sharon; Lee, Jinkook; Bloom, David E; Crimmins, Eileen; Seeman, Teresa

2015-01-01

This study aims to validate a modified dried blood spot (DBS)-based glycosylated hemoglobin (HbA1c) assay protocol, after a pretest in India showed poor correlation between the original DBS-based protocol and venous results. The original protocol was tested on different chemistry analyzers and then simplified at the University of Washington (UW). A second pretest was conducted in India to validate the modified assay protocol, using 44 quality control specimens. Data from UW indicated that, using the original protocol, the correlation coefficients between DBS and venous results were above 0.98 on both Bio-Rad and Olympus chemistry analyzers. The protocol worked equally well on filter paper, with or without pre-treatment, and when the recommended amount of blood spot material, or less, was used. A second pretest of the modified protocol confirmed that DBS-based levels from both Olympus and Roche chemistry analyzers were well correlated with DBS results from UW (correlation coefficients were above 0.96), as well as with venous values (correlation coefficients were above 0.94). The DBS-based HbA1c values are highly correlated with venous results. The pre-treatment of filter paper does not appear to be necessary. The poor results from the first pretest are probably due to factors unrelated to the protocol, such as problems with the chemistry analyzer or assay reagents. © 2015 Wiley Periodicals, Inc.

[Effects of blood glucose control on glucose variability and clinical outcomes in patients with severe acute pancreatitis in intensive care unit].

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Wu, Jing; Sun, Qiuhong; Yang, Hua

2015-05-19

To explore the effects of blood glucose control on glucose variability and clinical outcomes in patients with severe acute pancreatitis in intensive care unit (ICU). A total of 72 ICU patients with severe acute pancreatitis were recruited and divided randomly into observation and control groups (n = 36 each). Both groups were treated conventionally. And the observation group achieved stable blood glucose at 6.1-8.3 mmol/L with intensive glucose control. The length of ICU and hospital stays, ICU mortality rate, transit operative rate, concurrent infection rate, admission blood glucose, glycosylated hemoglobin, mean insulin dose, mean blood glucose, blood glucose value standard deviation (GLUSD), glycemic liability index (GLUGLI) and mean amplitude of glycemic excursion (GLUMAGE) of two groups were compared. At the same time, the relationship between blood glucose variability, ICU mortality rate and its predictive value were analyzed by correlation analysis and receiver operating characteristic curve (ROC). The lengths of ICU and hospital stays of observation group were all significantly less than those of the control group [(11.7 ± 9.9) vs (15.9 ± 8.02) days, (21.8 ± 10.8) vs (28.2 ± 12.7) days, P blood glucose value and GLUSD of observation group were significantly lower than those of control group [(7.4 ± 1.1) vs (9.6 ± 1.2), (1.8 ± 1.0) vs (2.5 ± 1.3) mmol/L]. The differences were statistically significant (P curve analysis showed that, AUC of GLUGLI was 0.748 and 95% CI 0.551-0.965 (P glucose control in patients with severe acute pancreatitis helps reduce the blood sugar fluctuations, lower the risks of infectious complications and promote the patient rehabilitation. And GLUGLI is positively correlated with ICU mortality rate. It has good predictive values.

Mortality in Individuals Aged 80 and Older with Type 2 Diabetes Mellitus in Relation to Glycosylated Hemoglobin, Blood Pressure, and Total Cholesterol.

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Hamada, Shota; Gulliford, Martin C

2016-07-01

To evaluate whether low glycosylated hemoglobin (HbA1c), blood pressure (BP), and total cholesterol (TC) are associated with lower risk of all-cause mortality in very old individuals with type 2 diabetes mellitus. Population-based cohort study. Primary care database in the United Kingdom. Individuals aged 80 and older with type 2 diabetes mellitus (N = 25,966). Associations between baseline HbA1c, BP, and TC and all-cause mortality were evaluated in Cox proportional hazards models. Analyses were adjusted for sex, age, duration of diabetes mellitus, lifestyle variables, HbA1c, BP, TC, comorbidities, prescribing of antidiabetic and cardiovascular drugs, and participants' general practice. There were 4,490 deaths during follow-up (median 2.0 years; mortality 104.7 per 1,000 person-years). Mortality in participants with low (type 2 diabetes mellitus. Further research is required to understand these associations and to identify optimal treatment targets in this population. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

INFLUENCE OF HERBAL EXTRACTS ON METABOLIC DISTURBANCES IN DIABETES MELLITUS AND INSULIN RESISTANCE MODEL

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T. V. Yakimova

2015-01-01

Full Text Available The aim of this research was to assess the influence on metabolic processes of herbal extracts, used in diets with different fat content, in diabetes mellitus and insulin resistance model.Material and methods. The experiments were performing on 90 noninbred male albino rats. Diabetes mellitus was modeling with twice-repeated intraperitoneal streptozotocine (30 mg/kg injections. For the insulin resistance formation animals were fad meal with 30% fat content. Against the background rats were administering into the stomach nettle leafs (Urtica dioica L., 100 mg/kg, burdock roots (Arctium lappa L., 25 mg/kg extracts or intraperitoneal insulin preparation Actrapide HM Penfill (3 mg/kg daily during 10 days. During period of agents introduction one-half of animals continued to receive food with high fat content, the other half received diet with 8% fat content. The third rats group received only food with low fat content without extracts or insulin administration. In blood was measured the glucose, glycosylated hemoglobin, creatinine, urea, uric acid content, in liver homogenates – glycogen, protein content, aminotransferases and glucose-6phosphatase activity, in muscle homogenates – glycogen and protein content.Results. After streptozotocine injections and diet with 30% fat content the blood glucose level became by 4.0–5.3 fold more than level of intact animals, increased the hemoglobin glycosylation, also creatinine, urea, uric acid blood content, in liver and muscle homogenates raised glycogen content, decreased protein quantity, in liver homogenates increased aminotranferases and glucose-6-phosphatase activity. In animals only feeding with 8% fat diminished hyperglycemia, creatinine blood retention, the liver glycogen content and recovered its protein resources. The nettle or burdock extracts administrating to animals that continued to receive high fat meal decreased the blood glucose, glycosylated hemoglobin and creatinine content, the liver

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

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Kandasamy, Neelamegam; Ashokkumar, Natarajan, E-mail: npashokkumar1@gmail.com

2014-09-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

International Nuclear Information System (INIS)

Kandasamy, Neelamegam; Ashokkumar, Natarajan

2014-01-01

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

Structural and Functional Consequences of Increased Tubulin Glycosylation in Diabetes Mellitus

Science.gov (United States)

Williams, Stuart K.; Howarth, Nancy L.; Devenny, James J.; Bitensky, Mark W.

1982-11-01

The extent of in vitro nonenzymatic glycosylation of purified rat brain tubulin was dependent on time and glucose concentration. Tubulin glycosylation profoundly inhibited GTP-dependent tubulin polymerization. Electron microscopy and NaDodSO4/polyacrylamide gel electrophoresis showed that glycosylated tubulin forms high molecular weight amorphous aggregates that are not disrupted by detergents or reducing agents. The amount of covalently bound NaB3H4-reducible sugars in tubulin recovered from brain of streptozotocin-induced diabetic rats was dramatically increased as compared with tubulin recovered from normal rat brain. Moreover, tubulin recovered from diabetic rat brain exhibited less GTP-induced polymerization than tubulin from nondiabetic controls. The possible implications of these data for diabetic neuropathy are discussed.

Monitoring HIV-infected Patients with Diabetes: Hemoglobin A1c, Fructosamine, or Glucose?

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So-Young Kim

2014-01-01

Full Text Available Background Published studies report inappropriately low hemoglobin A1C (HbA1c values that underestimate glycemia in HIV patients. Methods We reviewed the charts of all HIV patients with diabetes mellitus (DM at our clinic. Fifty-nine patients had HbA1c data, of whom 26 patients also had fructosamine data. We compared the most recent HbA1c to finger-stick (FS glucose averaged over three months, and fructosamine to FS averaged over six weeks. Predicted average glucose (pAG was calculated as reported by Nathan et al: pAG (mg/dL = 28.7 × A1C% – 46.7. Data were analyzed using the Statistical Analysis System (SAS and Kruskal–Wallis test. Results HbA1c values underestimated (UE actual average glucose (aAG in 19% of these patients and overestimated (OE aAG in 27%. HbA1c estimated aAG within the established range in only 54% of the patients. There were no statistical differences in the types of HIV medication used in patients with UE, OE, or accurately estimated (AE glycemia. A Spearman correlation coefficient between HbA1c and aAG was r = 0.53 ( P < 0.0001. Correlation between fructosamine and aAG was r = 0.47 ( P = 0.016. Conclusions The correlations between HbA1c and aAG and between fructosamine and aAG were weaker than expected, and fructosamine was not more accurate than HbA1c.

Crystallization and preliminary crystallographic analysis of human glycosylated haemoglobin

International Nuclear Information System (INIS)

Syakhovich, Vitaly E.; Saraswathi, N. T.; Ruff, Marc; Bokut, Sergey B.; Moras, Dino

2006-01-01

Non enzymatic modification of haemoglobin by glucose plays an important role in diabetes pathogenesis. Here the purification, characterization and crystallization of human glycosylated haemoglobin are reported. Human glycosylated haemoglobin A 1C is a stable minor variant formed in vivo by post-translational modification of the main form of haemoglobin by glucose. Crystals of oxyHbA 1C were obtained using the hanging-drop vapour-diffusion method and PEG as precipitant. The diffraction pattern of the crystal extends to a resolution of 2.3 Å at 120 K. The crystals belong to space group C2, with unit-cell parameters a = 237.98, b = 59.27, c = 137.02 Å, α = 90.00, β = 125.40, γ = 90.00°. The presence of two and a half molecules per asymmetric unit gives a crystal volume per protein weight (V M ) of 9.70 Å 3 Da −1 and a solvent content of 49%

Crystallization and preliminary crystallographic analysis of human glycosylated haemoglobin

Energy Technology Data Exchange (ETDEWEB)

Syakhovich, Vitaly E. [Department of Biochemistry and Biophysics, International Sakharov Environmental University, Dolgobrodskaya St 23, 220009 Minsk (Belarus); Saraswathi, N. T.; Ruff, Marc, E-mail: ruff@igbmc.u-strasbg.fr [Département de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch (France); Bokut, Sergey B. [Department of Biochemistry and Biophysics, International Sakharov Environmental University, Dolgobrodskaya St 23, 220009 Minsk (Belarus); Moras, Dino [Département de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch (France); Department of Biochemistry and Biophysics, International Sakharov Environmental University, Dolgobrodskaya St 23, 220009 Minsk (Belarus)

2006-02-01

Non enzymatic modification of haemoglobin by glucose plays an important role in diabetes pathogenesis. Here the purification, characterization and crystallization of human glycosylated haemoglobin are reported. Human glycosylated haemoglobin A{sub 1C} is a stable minor variant formed in vivo by post-translational modification of the main form of haemoglobin by glucose. Crystals of oxyHbA{sub 1C} were obtained using the hanging-drop vapour-diffusion method and PEG as precipitant. The diffraction pattern of the crystal extends to a resolution of 2.3 Å at 120 K. The crystals belong to space group C2, with unit-cell parameters a = 237.98, b = 59.27, c = 137.02 Å, α = 90.00, β = 125.40, γ = 90.00°. The presence of two and a half molecules per asymmetric unit gives a crystal volume per protein weight (V{sub M}) of 9.70 Å{sup 3} Da{sup −1} and a solvent content of 49%.

Stannylene‐Mediated Regioselective 6‐O‐Glycosylation of Unprotected Phenyl 1‐Thioglycopyranosides

DEFF Research Database (Denmark)

Maggi, Agnese; Madsen, Robert

2013-01-01

acetal, and then subjected to selective glycosylation at the 6‐position with the Koenigs–Knorr protocol. Peracylated glycosyl bromides of D‐glucose, D‐galactose, D‐mannose and D‐glucosamine were employed as the donors to give the corresponding (1→6)‐linked disaccharides in moderate to good yields......‐thio‐β‐D‐glucopyranoside gave rise to the corresponding (1→6)‐linked trisaccharides in moderate yields....

The relative contribution of mannose salvage pathways to glycosylation in PMI-deficient mouse embryonic fibroblast cells.

Science.gov (United States)

Fujita, Naonobu; Tamura, Ayako; Higashidani, Aya; Tonozuka, Takashi; Freeze, Hudson H; Nishikawa, Atsushi

2008-02-01

Mannose for mammalian glycan biosynthesis can be imported directly from the medium, derived from glucose or salvaged from endogenous or external glycans. All pathways must generate mannose 6-phosphate, the activated form of mannose. Imported or salvaged mannose is directly phosphorylated by hexokinase, whereas fructose 6-phosphate from glucose is converted to mannose 6-phosphate by phosphomannose isomerase (PMI). Normally, PMI provides the majority of mannose for glycan synthesis. To assess the contribution of PMI-independent pathways, we used PMI-null fibroblasts to study N-glycosylation of DNase I, a highly sensitive indicator protein. In PMI-null cells, imported mannose and salvaged mannose make a significant contribution to N-glycosylation. When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated. Adding approximately 13 microm mannose to the medium completely restored normal glycosylation. Treatment with bafilomycin A(1), an inhibitor of lysosomal acidification, also markedly reduced N-glycosylation of DNase I, but in this case only 8 microm mannose was required to restore full glycosylation, indicating that a nonlysosomal source of mannose made a significant contribution. Glycosylation levels were greatly also reduced in glycoconjugate-free medium, when endosomal membrane trafficking was blocked by expression of a mutant SKD1. From these data, we conclude that PMI-null cells can salvage mannose from both endogenous and external glycoconjugates via lysosomal and nonlysosomal degradation pathways.

Point-of-Care Versus Central Laboratory Measurements of Hemoglobin, Hematocrit, Glucose, Bicarbonate and Electrolytes: A Prospective Observational Study in Critically Ill Patients.

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Jérôme Allardet-Servent

Full Text Available Rapid detection of abnormal biological values using point-of-care (POC testing allows clinicians to promptly initiate therapy; however, there are concerns regarding the reliability of POC measurements. We investigated the agreement between the latest generation blood gas analyzer and central laboratory measurements of electrolytes, bicarbonate, hemoglobin, hematocrit, and glucose.314 paired samples were collected prospectively from 51 critically ill patients. All samples were drawn simultaneously in the morning from an arterial line. BD Vacutainer tubes were analyzed in the central laboratory using Beckman Coulter analyzers (AU 5800 and DxH 800. BD Preset 3 ml heparinized-syringes were analyzed immediately in the ICU using the POC Siemens RAPIDPoint 500 blood gas system. We used CLIA proficiency testing criteria to define acceptable analytical performance and interchangeability.Biases, limits of agreement (±1.96 SD and coefficients of correlation were respectively: 1.3 (-2.2 to 4.8 mmol/L, r = 0.936 for sodium; 0.2 (-0.2 to 0.6 mmol/L, r = 0.944 for potassium; -0.9 (-3.7 to 2 mmol/L, r = 0.967 for chloride; 0.8 (-1.9 to 3.4 mmol/L, r = 0.968 for bicarbonate; -11 (-30 to 9 mg/dL, r = 0.972 for glucose; -0.8 (-1.4 to -0.2 g/dL, r = 0.985 for hemoglobin; and -1.1 (-2.9 to 0.7%, r = 0.981 for hematocrit. All differences were below CLIA cut-off values, except for hemoglobin.Compared to central Laboratory analyzers, the POC Siemens RAPIDPoint 500 blood gas system satisfied the CLIA criteria of interchangeability for all tested parameters, except for hemoglobin. These results are warranted for our own procedures and devices. Bearing these restrictions, we recommend clinicians to initiate an appropriate therapy based on POC testing without awaiting a control measurement.

Point-of-Care Versus Central Laboratory Measurements of Hemoglobin, Hematocrit, Glucose, Bicarbonate and Electrolytes: A Prospective Observational Study in Critically Ill Patients.

Science.gov (United States)

Allardet-Servent, Jérôme; Lebsir, Melissa; Dubroca, Christian; Fabrigoule, Martine; Jordana, Sylvie; Signouret, Thomas; Castanier, Matthias; Thomas, Guillemette; Soundaravelou, Rettinavelou; Lepidi, Anne; Delapierre, Laurence; Penaranda, Guillaume; Halfon, Philippe; Seghboyan, Jean-Marie

2017-01-01

Rapid detection of abnormal biological values using point-of-care (POC) testing allows clinicians to promptly initiate therapy; however, there are concerns regarding the reliability of POC measurements. We investigated the agreement between the latest generation blood gas analyzer and central laboratory measurements of electrolytes, bicarbonate, hemoglobin, hematocrit, and glucose. 314 paired samples were collected prospectively from 51 critically ill patients. All samples were drawn simultaneously in the morning from an arterial line. BD Vacutainer tubes were analyzed in the central laboratory using Beckman Coulter analyzers (AU 5800 and DxH 800). BD Preset 3 ml heparinized-syringes were analyzed immediately in the ICU using the POC Siemens RAPIDPoint 500 blood gas system. We used CLIA proficiency testing criteria to define acceptable analytical performance and interchangeability. Biases, limits of agreement (±1.96 SD) and coefficients of correlation were respectively: 1.3 (-2.2 to 4.8 mmol/L, r = 0.936) for sodium; 0.2 (-0.2 to 0.6 mmol/L, r = 0.944) for potassium; -0.9 (-3.7 to 2 mmol/L, r = 0.967) for chloride; 0.8 (-1.9 to 3.4 mmol/L, r = 0.968) for bicarbonate; -11 (-30 to 9 mg/dL, r = 0.972) for glucose; -0.8 (-1.4 to -0.2 g/dL, r = 0.985) for hemoglobin; and -1.1 (-2.9 to 0.7%, r = 0.981) for hematocrit. All differences were below CLIA cut-off values, except for hemoglobin. Compared to central Laboratory analyzers, the POC Siemens RAPIDPoint 500 blood gas system satisfied the CLIA criteria of interchangeability for all tested parameters, except for hemoglobin. These results are warranted for our own procedures and devices. Bearing these restrictions, we recommend clinicians to initiate an appropriate therapy based on POC testing without awaiting a control measurement.

The association between estimated average glucose levels and fasting plasma glucose levels

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Giray Bozkaya

2010-01-01

Full Text Available OBJECTIVE: The level of hemoglobin A1c (HbA1c, also known as glycated hemoglobin, determines how well a patient's blood glucose level has been controlled over the previous 8-12 weeks. HbA1c levels help patients and doctors understand whether a particular diabetes treatment is working and whether adjustments need to be made to the treatment. Because the HbA1c level is a marker of blood glucose for the previous 120 days, average blood glucose levels can be estimated using HbA1c levels. Our aim in the present study was to investigate the relationship between estimated average glucose levels, as calculated by HbA1c levels, and fasting plasma glucose levels. METHODS: The fasting plasma glucose levels of 3891 diabetic patient samples (1497 male, 2394 female were obtained from the laboratory information system used for HbA1c testing by the Department of Internal Medicine at the Izmir Bozyaka Training and Research Hospital in Turkey. These samples were selected from patient samples that had hemoglobin levels between 12 and 16 g/dL. The estimated glucose levels were calculated using the following formula: 28.7 x HbA1c - 46.7. Glucose and HbA1c levels were determined using hexokinase and high performance liquid chromatography (HPLC methods, respectively. RESULTS: A strong positive correlation between fasting plasma glucose levels and estimated average blood glucose levels (r=0.757, p<0.05 was observed. The difference was statistically significant. CONCLUSION: Reporting the estimated average glucose level together with the HbA1c level is believed to assist patients and doctors determine the effectiveness of blood glucose control measures.

Production, crystallization and X-ray characterization of chemically glycosylated hen egg-white lysozyme

International Nuclear Information System (INIS)

López-Jaramillo, F. J.; Pérez-Banderas, F.; Hernández-Mateo, F.; Santoyo-González, F.

2005-01-01

The feasibility of glycosylation post-purification has been demonstrated by introducing glucose into the model protein lysozyme via a novel reaction that is compatible with biological samples. The crystallization of glycoproteins is one of the challenges to be confronted by the crystallographic community in the frame of what is known as glycobiology. The state of the art for the crystallization of glycoproteins is not promising and removal of the carbohydrate chains is generally suggested since they are flexible and a source of heterogeneity. In this paper, the feasibility of introducing glucose into the model protein hen egg-white lysozyme via a post-purification glycosylation reaction that may turn any protein into a model glycoprotein whose carbohydrate fraction can be manipulated is demonstrated

Efficacy of the Hydroalcoholic Extract of Tribulus terrestris on the Serum Glucose and Lipid Profile of Women With Diabetes Mellitus: A Double-Blind Randomized Placebo-Controlled Clinical Trial.

Science.gov (United States)

Samani, Nasrin Babadaei; Jokar, Azam; Soveid, Mahmood; Heydari, Mojtaba; Mosavat, Seyed Hamdollah

2016-10-01

Considering traditional use of Tribulus terrestris in diabetes and proven antihyperglycemic and antihyperlipidemic effects of T terrestris in animal studies, we aimed to evaluate the efficacy of the hydroalcoholic extract of T terrestris on the serum glucose and lipid profile of women with non-insulin-dependent diabetes mellitus. Ninety-eight women with diabetes mellitus type 2 were randomly allocated to receive the T terrestris (1000 mg/d) or placebo for 3 months. The patients were evaluated in terms of the fasting blood glucose, 2-hour postprandial glucose, glycosylated hemoglobin, and lipid profile. Tribulus terrestris showed a significant blood glucose-lowering effect in diabetic women compared to placebo (P terrestris group was significantly reduced compared with placebo, while no significant effect was observed in the triglyceride and high-density lipoprotein levels. The study showed preliminary promising hypoglycemic effect of T terrestris in women with diabetes mellitus type 2. © The Author(s) 2016.

Association of glycosylated hemoglobin (HbA1c) levels with Iinsulin ...

African Journals Online (AJOL)

Material and Methods: This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. ... Plasma glucose levels were measured by the glucose oxidase method. Plasma ... resistance, a condition that can cause diabetes mellitus ... resistance was estimated by using the homeostasis.

Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin: A Prospective Cohort Study.

Science.gov (United States)

Li, Xue; Pang, Xiuyu; Zhang, Qiao; Qu, Qiannuo; Hou, Zhigang; Liu, Zhipeng; Lv, Lin; Na, Guanqiong; Zhang, Wei; Sun, Changhao; Li, Ying

2016-02-01

This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels.A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index.After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend HOMA-IR index in the entire cohort, men, and women were 1.33 (1.10-1.62), 1.46 (1.08-1.98), and 1.47 (1.12-1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24-3.51; HR = 4.00, 95% CI = 2.03-7.90; and HR = 2.05, 95% CI = 1.29-3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48-3.02; and HR = 1.35, 95% CI = 1.10-1.65, respectively).Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping HOMA-IR index.

Glycosylation Helps Cellulase Enzymes Bind to Plant Cell Walls (Fact Sheet)

Energy Technology Data Exchange (ETDEWEB)

2012-06-01

Computer simulations suggest a new strategy to design enhanced enzymes for biofuels production. Large-scale computer simulations predict that the addition of glycosylation on carbohydrate-binding modules can dramatically improve the binding affinity of these protein domains over amino acid mutations alone. These simulations suggest that glycosylation can be used as a protein engineering tool to enhance the activity of cellulase enzymes, which are a key component in the conversion of cellulose to soluble sugars in the production of biofuels. Glycosylation is the covalent attachment of carbohydrate molecules to protein side chains, and is present in many proteins across all kingdoms of life. Moreover, glycosylation is known to serve a wide variety of functions in biological recognition, cell signaling, and metabolism. Cellulase enzymes, which are responsible for deconstructing cellulose found in plant cell walls to glucose, contain glycosylation that when modified can affect enzymatic activity-often in an unpredictable manner. To gain insight into the role of glycosylation on cellulase activity, scientists at the National Renewable Energy Laboratory (NREL) used computer simulation to predict that adding glycosylation on the carbohydrate-binding module of a cellulase enzyme dramatically boosts the binding affinity to cellulose-more than standard protein engineering approaches in which amino acids are mutated. Because it is known that higher binding affinity in cellulases leads to higher activity, this work suggests a new route to designing enhanced enzymes for biofuels production. More generally, this work suggests that tuning glycosylation in cellulase enzymes is a key factor to consider when engineering biochemical conversion processes, and that more work is needed to understand how glycosylation affects cellulase activity at the molecular level.

Fluorine-Directed Glycosylation Enables the Stereocontrolled Synthesis of Selective SGLT2 Inhibitors for Type II Diabetes.

Science.gov (United States)

Sadurní, Anna; Kehr, Gerald; Ahlqvist, Marie; Wernevik, Johan; Sjögren, Helena Peilot; Kankkonen, Cecilia; Knerr, Laurent; Gilmour, Ryan

2018-02-26

Inhibition of the sodium-glucose co-transporters (SGLT1 and SGLT2) is a validated strategy to address the increasing prevalence of type II diabetes mellitus. However, achieving selective inhibition of human SGLT1 or SGLT2 remains challenging. Orally available small molecule drugs based on the d-glucose core of the natural product Gliflozin have proven to be clinically effective in this regard, effectively impeding glucose reabsorption. Herein, we disclose the influence of molecular editing with fluorine at the C2 position of the pyranose ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga ® ) to concurrently direct β-selective glycosylation, as is required for biological efficacy, and enhance aspects of the physicochemical profile. Given the abundance of glycosylated pharmaceuticals in diabetes therapy that contain a β-configured d-glucose nucleus, it is envisaged that this strategy may prove to be expansive. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isotope effects in the non enzymic glucation of hemoglobin catalyzed by phosphate

International Nuclear Information System (INIS)

Gil, H.; Mata-Segreda, J.; Schowen, R.

1991-01-01

The reaction of hemoglobin, mainly at the N-terminal valine, with glucose exhibits identical rates in protium and deuterium oxides, both for the buffer-independent rate and for the first-order rate in phosphate buffer. Under the conditions employed, imine formation is relatively rapid and events in the course of the Amadori rearrangement must limit the rate. A very-slow, phosphate-induced reorganization of hemoglobin-glucose imine may be the most likely candidate for the rate-limiting step. (author)

Glycosylation Engineering

DEFF Research Database (Denmark)

Clausen, Henrik; Wandall, Hans H.; Steentoft, Catharina

2017-01-01

Knowledge of the cellular pathways of glycosylation across phylogeny provides opportunities for designing glycans via genetic engineering in a wide variety of cell types including bacteria, fungi, plant cells, and mammalian cells. The commercial demand for glycosylation engineering is broad......, including production of biological therapeutics with defined glycosylation (Chapter 57). This chapter describes how knowledge of glycan structures and their metabolism (Parts I–III of this book) has led to the current state of glycosylation engineering in different cell types. Perspectives for rapid...

ECM Proteins Glycosylation and Relation to Diabetes

Science.gov (United States)

Pernodet, Nadine; Bloomberg, Ayla; Sood, Vandana; Slutsky, Lenny; Ge, Shouren; Clark, Richard; Rafailovich, Miriam

2004-03-01

The chemical modification and crosslinking of proteins by sugar glycosylation contribute to the aging of tissue proteins, and acceleration of this reaction during hyperglycemia is implicated in the pathogenesis of diabetic complications, such as disorder of the wound healing. Advanced glycation endproducts (AGEs) formation and protein crosslinking are irreversible processes that alter the structural and functional properties of proteins, lipid components and nucleic acids. And the mechanism, by which it happens, is not clear. Fibrinogen and fibronectin are plasma proteins, which play a major role in human wound healing. Fibrinogen converts to an insoluble fibrin "gel" following a cut, which eventually forms a clot to prevent blood loss, to direct cell adhesion and migration for forming scars. Fibronectin is a critical protein for cell adhesion and migration in wound healing. The effects of glucose on the binding of these plasma proteins from the extra cellular matrix (ECM) were followed at different concentrations by atomic force microscopy and lateral force modulation to measure the mechanical response of the samples. Glucose solutions (1, 2, and 3mg/mL) were incubated with the protein (100 mg/ml) and silicon (Si) substrates spun with sulfonated polystyrene (SPS) 28% for five days. Data showed that not only the organization of the protein on the surface was affected but also its mechanical properties. At 3 mg/mL glucose, Fn fibers were observed to be harder than those of the control, in good agreement with our hypothesis that glycosylation hardens tissues by crosslinking of proteins in the ECM and might cause fibers to break more easily.

Antiangiogenic activity of 2-deoxy-D-glucose.

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Jaime R Merchan

2010-10-01

Full Text Available During tumor angiogenesis, endothelial cells (ECs are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR, which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay. Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETAT(AG transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies.

Antidiabetic effect of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats

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B. Jayaprasad

2016-03-01

Full Text Available Diabetes has been increasing at an alarming rate around the world, and experts have relied on remedies from the utilization of ancient drugs that are essentially derived from plants. The present study aimed to evaluate the antidiabetic potential of Chloroxylon swietenia bark extracts on streptozotocin induced diabetic rats. Diabetes was induced in male albino Wistar rats by single intraperitoneal injection of streptozotocin (STZ (50 mg/kg b.w.. The diabetic rats were administered orally with C. swietenia bark (CSB methanolic (CSBMEt and aqueous (CSBAEt (250 mg/kg b.w. extracts and glibenclamide (600 µg/kg b.w. by intragastric intubation for 45 days. The result showed a heavy loss in weight, increase in blood glucose and glycosylated hemoglobin level, and decline in plasma insulin and total hemoglobin content. Furthermore, glucose-6-phosphatase and fructose-1,6-bis phosphatase were found to be increased whereas hexokinase and glycogen contents were decreased in STZ induced diabetic rats. CSBAEt, CSBMEt and glibenclamide treated diabetic rats showed moderate reduction in blood glucose and glycosylated hemoglobin levels; in addition, plasma insulin and hemoglobin levels were elevated. The altered activities of carbohydrate metabolizing enzymes and liver glycogen were improved remarkably. CSBMEt results were comparable to the standard drug glibenclamide. The present findings support the usage of the plant extracts for the traditional treatment of diabetes.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

Science.gov (United States)

Murphy, P A; Cebula, T A; Windle, B E

1981-10-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of all the forms of endogenous pyrogen. When cells were stimulated in the presence of 3H-labeled amino acids and 14C-labeled glucosamine or glucose, the purified pyrogens were labeled with 3H but not with 14C. Macrophage membrane preparations were made which contained glycosyl transferases and could transfer sugar residues from sugar nucleotides to deglycosylated fetuin. These macrophage membrane preparations did not transfer sugars to the pI 7.3 endogenous pyrogen. Treatment of endogenous pyrogens with neuraminidase or with periodate produced no evidence suggesting that the pyrogens were glycosylated. Last, endogenous pyrogens did not bind to any of four lectins with different carbohydrate specificities. This evidence suggests that the heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylation and must have some other cause.

Overelaborated synaptic architecture and reduced synaptomatrix glycosylation in a Drosophila classic galactosemia disease model

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Patricia Jumbo-Lucioni

2014-12-01

Full Text Available Classic galactosemia (CG is an autosomal recessive disorder resulting from loss of galactose-1-phosphate uridyltransferase (GALT, which catalyzes conversion of galactose-1-phosphate and uridine diphosphate (UDP-glucose to glucose-1-phosphate and UDP-galactose, immediately upstream of UDP–N-acetylgalactosamine and UDP–N-acetylglucosamine synthesis. These four UDP-sugars are essential donors for driving the synthesis of glycoproteins and glycolipids, which heavily decorate cell surfaces and extracellular spaces. In addition to acute, potentially lethal neonatal symptoms, maturing individuals with CG develop striking neurodevelopmental, motor and cognitive impairments. Previous studies suggest that neurological symptoms are associated with glycosylation defects, with CG recently being described as a congenital disorder of glycosylation (CDG, showing defects in both N- and O-linked glycans. Here, we characterize behavioral traits, synaptic development and glycosylated synaptomatrix formation in a GALT-deficient Drosophila disease model. Loss of Drosophila GALT (dGALT greatly impairs coordinated movement and results in structural overelaboration and architectural abnormalities at the neuromuscular junction (NMJ. Dietary galactose and mutation of galactokinase (dGALK or UDP-glucose dehydrogenase (sugarless genes are identified, respectively, as critical environmental and genetic modifiers of behavioral and cellular defects. Assaying the NMJ extracellular synaptomatrix with a broad panel of lectin probes reveals profound alterations in dGALT mutants, including depletion of galactosyl, N-acetylgalactosamine and fucosylated horseradish peroxidase (HRP moieties, which are differentially corrected by dGALK co-removal and sugarless overexpression. Synaptogenesis relies on trans-synaptic signals modulated by this synaptomatrix carbohydrate environment, and dGALT-null NMJs display striking changes in heparan sulfate proteoglycan (HSPG co-receptor and Wnt

Self-regulating insulin delivery systems I. Synthesis and characterization of glycosylated insulin

NARCIS (Netherlands)

Jeong, Seo Young; Kim, Sung Wan; Eenink, Martinus J.D.; Feijen, Jan

1984-01-01

A design for a self-regulating insulin delivery system based on the competitive binding of glucose and glycosylated insulin to the lectin Concanavalin A is proposed. A differnt approach to diabetes therapy is the attempt to effect a permanent cure of the disease by supplementing the patient's

[Levels of glycosylated hemoglobin and the difference in the cost of health care for diabetic patients: an econometric study].

Science.gov (United States)

Lenz, Rony; Zarate, Aldo; Rodríguez, Jorge; Ramírez, Jorge

2014-07-01

Complications increase treatment costs of diabetes mellitus (DM). An adequate metabolic control of the disease could reduce these costs. To evaluate the costs of medical care for a cohort of patients with DM, according to their degree of metabolic compensation. All diabetic patients attended in a regional hospital from 2005 to 2010 were analyzed. A correlational study between costs of individual healthcare and levels of glycosylated hemoglobin (HbA1c), was performed in a series of annual cross-sectional measurements. The study comprised 1,644 diabetic patients. During the study period the average cost of healthcare per patient increased from $878,000 to more than $1,000,000 Chilean pesos (CLP) during the study period. The percentage of patients with HbA1c levels below 7.0% varied between 43.0% and 54.9%. Costs for patients with HbA1c levels between 7 and 8.9% were 1.3 to 1.5 times greater. For the group of patients with HbA1c levels between 9 and 10.9% the costs increased 1.4 to 1.6 times. For patients with HbA1c levels greater than 11.0%, healthcare costs doubled. Healthcare expenditure varied according to metabolic control, which is consistent with international findings. This study was limited by its selected population, incomplete information on health expenditures, and the inclusion of only direct costs to the health system. If all patients would achieve metabolic compensation, the yearly savings would be CLP $308,000,000 (or USD $657,000).

Elevated 1-hour postload plasma glucose levels identify subjects with normal glucose tolerance but impaired β-cell function, insulin resistance, and worse cardiovascular risk profile: the GENFIEV study.

Science.gov (United States)

Bianchi, Cristina; Miccoli, Roberto; Trombetta, Maddalena; Giorgino, Francesco; Frontoni, Simona; Faloia, Emanuela; Marchesini, Giulio; Dolci, Maria A; Cavalot, Franco; Cavallo, Gisella; Leonetti, Frida; Bonadonna, Riccardo C; Del Prato, Stefano

2013-05-01

In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis. The purpose of this study was to evaluate β-cell function, insulin resistance, and cardiovascular risk profile in subjects with NGT with a 1-h OGTT glucose of >155 mg/dL. The GENFIEV (Genetics, PHYsiopathology, and Evolution of Type 2 diabetes) study is a multicenter study recruiting individuals at high risk of T2DM. A total of 926 subjects underwent a 75-g OGTT for assessment of plasma glucose and C-peptide for mathematical modeling of β-cell function (derivative and proportional control). Fasting insulin, lipid profile, and clinical parameters were determined as well. A 1-hour OGTT glucose of >155 mg/dL was found in 39% of subjects with NGT, 76% with impaired fasting glucose (IFG), 90% with impaired glucose tolerance (IGT), and 99% and 98% with IFG + IGT or newly diagnosed T2DM, respectively. Among subjects with NGT (n = 474), those with 1-hour OGTT glucose of >155 mg/dL were more insulin-resistant and had worse β-cell function than those with 1-hour OGTT glucose of ≤155 mg/dL. Moreover, glycosylated hemoglobin, blood pressure, low-density lipoprotein cholesterol, and triglycerides were higher in subjects with NGT with 1-hour OGTT glucose of >155 mg/dL, whereas high-density lipoprotein cholesterol was lower compared with that in subjects with NGT with 1-hour OGTT glucose of ≤155 mg/dL. Compared with subjects with IGT, those with NGT with 1-hour OGTT glucose of >155 mg/dL had comparable cardiovascular risk profile and insulin resistance but slightly better β-cell function. Among subjects with NGT, those with 1-hour OGTT glucose of >155 mg/dL showed lower insulin sensitivity, impaired β-cell function, and worse cardiovascular risk profile and therefore are at greater risk of developing T2DM and cardiovascular disease.

Antihyperglycemic activity of Piper betle leaf on streptozotocin-induced diabetic rats.

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Santhakumari, P; Prakasam, A; Pugalendi, K V

2006-01-01

Piper betle, an indigenous medicinal plant, has a folk (Siddha and Ayurvedha) reputation in the rural southern India. The present study was carried out to evaluate the effect of P. betle on glucose metabolism since it is consumed as betel-quid after meals. Plasma levels of glucose and glycosylated hemoglobin and activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in control and streptozotocin (STZ) diabetic rats were assayed. Oral administration of leaf suspension of P. betle (75 and 150 mg/kg of body weight) for 30 days resulted in significant reduction in blood glucose (from 205.00 +/- 10.80 mg/dL to 151.30 +/- 6.53 mg/dL) and glycosylated hemoglobin and decreased activities of liver glucose-6-phosphatase and fructose-1,6-bisphosphatase, while liver hexokinase increased (P betle at a dose of 75 mg/kg of body weight exhibited better sugar reduction than 150 mg/kg of body weight. In addition, protection against body weight loss of diabetic animals was also observed. The effects produced by P. betle were compared with the standard drug glibenclamide. Thus, the present study clearly shows that P. betle intake influences glucose metabolism beneficially.

Diagnostic Accuracies of Glycated Hemoglobin, Fructosamine, and Homeostasis Model Assessment of Insulin Resistance in Predicting Impaired Fasting Glucose, Impaired Glucose Tolerance, or New Onset Diabetes After Transplantation.

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Rosettenstein, Kerri; Viecelli, Andrea; Yong, Kenneth; Nguyen, Hung Do; Chakera, Aron; Chan, Doris; Dogra, Gursharan; Lim, Ee Mun; Wong, Germaine; Lim, Wai H

2016-07-01

New onset diabetes after transplantation (NODAT) is associated with a 3-fold greater risk of cardiovascular disease events, with early identification and treatment potentially attenuating this risk. The optimal screening test to identify those with NODAT remains unclear, and the aim of this study was to examine the diagnostic accuracies of 4 screening tests in identifying impaired fasting glucose, impaired glucose tolerance (IGT), and NODAT. This is a single-center prospective cohort study of 83 nondiabetic kidney transplant recipients between 2008 and 2011. Oral glucose tolerance test was considered the gold standard in identifying IFG/IGT or NODAT. Diagnostic accuracies of random blood glucose, glycated hemoglobin (HBA1c), fructosamine, and Homeostasis Model Assessment-Insulin Resistance in predicting IFG/IGT or NODAT were assessed using the area under the receiver operating characteristic curve. Forty (48%) recipients had IFG/IGT or NODAT. Compared with HBA1c with adjusted area under the curve (AUC) of 0.88 (95% confidence interval [95% CI], 0.77-0.93), fructosamine was the most accurate test with adjusted AUC of 0.92 (95% CI, 0.83-0.96). The adjusted AUCs of random blood glucose and Homeostasis Model Assessment-Insulin Resistance in identifying IFG/IGT were between 0.81 and 0.85. Restricting to identifying IGT/NODAT using 2-hour oral glucose tolerance test (n = 66), fructosamine was the most accurate diagnostic test with adjusted AUC of 0.93 (95% CI, 0.84-0.99), but not statistically different to HBA1c with adjusted AUC of 0.88 (95% CI, 0.76-0.96). Although HBA1c is an acceptable and widely used screening test in detecting IFG/IGT or NODAT, fructosamine may be a more accurate diagnostic test but this needs to be further examined in larger cohorts.

[Type 2 diabetes mellitus: new treatments].

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Ascaso, Juan F

2014-08-04

The benefits and problems associated with traditional hypoglycemic drugs, such as failure of beta cells, hypoglycemia and weight gain, that lead to a worsening of diabetes, are reviewed. New hypoglycemic drugs with incretin effect (glucagon-like peptide-1 agonists and dipeptidyl peptidase 4 inhibitors), achieve, in a glucose dependent manner, an glycosylated hemoglobin reduction without hypoglycemia or increase in body weight. Recently, another group of oral hypoglycemic drugs, sodium-glucose cotransporter type 2 inhibitors, have demonstrated efficacy in diabetes control by inhibiting renal glucose reabsorption. However, long-term effects and cardiovascular prevention remain to be demonstrated. We have more and better drugs nowadays. Hypoglycemic treatment should be customized (glycosylated hemoglobin levels, risk-benefit, risk of hypoglycemia, weight changes, cardiovascular risk), with a combination of drugs being necessary in most cases. However, we do not have yet an ideal hypoglycemic drug. Moreover we must remember that an early and intensive treatment of dyslipidemia and hypertension is essential for the prevention of cardiovascular disease in patients with type 2 diabetes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

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Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

Effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome after radical gastrectomy.

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Sun, Li; Zhou, Pingping; Hua, Qingli; Jin, Changming; Guo, Chunling; Song, Bing

2018-06-01

This study aimed to investigate the effects of blood glucose, blood lipids and blood pressure control on recovery of patients with gastric cancer complicated with metabolic syndrome (MS) after radical gastrectomy. A total of 150 patients with gastric cancer, who were treated in Daqing Longnan Hospital from November, 2015 to May, 2017, were enrolled in this study. The patients were divided into the MS group (80 cases) and non-MS group (70 cases). Patients in the MS group were given corresponding drugs to control blood pressure, blood lipids and blood glucose, while patients in the non-MS group were not treated with those drugs. Patients in the MS group were divided into the normal and abnormal groups according to the levels of blood glucose, blood lipids and blood pressure. Moreover, occurrences of complications were compared between the normal and abnormal groups. Before surgery, blood glucose, blood lipids and blood pressure in the MS group were significantly higher than those in the non-MS group (pblood glucose, blood lipids and blood pressure of the MS group decreased significantly compared to those before operation (pblood glucose, 2 h postprandial blood glucose, glycosylated hemoglobin, total triglycerides (TGs), LDL, mean blood pressure and BMI (pblood glucose, blood lipids and blood pressure in patients with gastric cancer complicated with MS after radical gastrectomy can reduce the incidence of postoperative complications and promote postoperative recovery.

Glucose transport in brain - effect of inflammation.

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Jurcovicova, J

2014-01-01

Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma

Assessment risk of osteoporosis in Chinese people: relationship among body mass index, serum lipid profiles, blood glucose, and bone mineral density

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Cui RT

2016-07-01

Full Text Available Rongtao Cui,1 Lin Zhou,2 Zuohong Li,2 Qing Li,2 Zhiming Qi,2 Junyong Zhang3 1Department of Orthopedic and Trauma Surgery, Surgical Research, Duisburg-Essen University Hospital, Essen, Germany; 2Department of Orthopedics, Dalian Central Hospital, Dalian, 3Department of Gastroenterology, Shandong Provincial Hospital, Jinan, People’s Republic of China Objective: The aim of our study was to investigate the relationship among age, sex, body mass index (BMI, serum lipid profiles, blood glucose (BG, and bone mineral density (BMD, making an assessment of the risk of osteoporosis.Materials and methods: A total of 1,035 male and 3,953 female healthy volunteers (aged 41–95 years were recruited by an open invitation. The basic information, including age, sex, height, weight, waistline, hipline, menstrual cycle, and medical history, were collected by a questionnaire survey and physical examination. Serum lipid profiles, BG, postprandial blood glucose, and glycosylated hemoglobin were obtained after 12 hours fasting. BMD in lumbar spine was measured by dual-energy X-ray absorptiometry scanning.Results: The age-adjusted BMD in females was significantly lower than in males. With aging, greater differences of BMD distribution exist in elderly females than in males (P<0.001, and the fastigium of bone mass loss was in the age range from 51 to 55 in females and from 61 to 65 years in males. After adjustment for sex, there were significant differences in BMD among BMI-stratified groups in both males and females. The subjects with a BMI of <18.5 had a higher incidence of osteoporosis than BMI ≥18.5 in both sexes. BMD in type 2 diabetes mellitus with a BG of >7.0 mmol/L was lower than in people with BG of ≤7.0 mmol/L (P<0.001. People with serum high-density lipoprotein cholesterol levels of ≥1.56 mmol/L had a greater prevalence of osteoporosis compared with high-density lipoprotein cholesterol ≤1.55 mmol/L. Logistic regression with odds ratios showed that

Effect of hypoxia on glucose metabolism in nondiabetic patients with obstructive sleep apnea syndrome.

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Sökücü, Sinem Nedime; Karasulu, Levent; Dalar, Levent; Ozdemir, Cengiz; Seyhan, Ekrem Cengiz; Aydin, Senay; Altin, Sedat

2013-08-01

Obstructive sleep apnea syndrome (OSAS) may promote hyperglycemia and insulin resistance. Our aim is to investigate the effect of OSAS on the fasting plasma glucose, glycosylated hemoglobin (HbA1c), and C reactive protein (CRP) in nondiabetic patients. Blood parameters of consecutive 90 non diabetic patients whom polysomnografic evaluations were done in our sleep laboratory was evaluated. Among these 61 patients with normal fasting blood glucose were classified due to their apne-hipopnea index (AHI) as mild (n=16, 26.2%), moderate (n=18, 29.5%) and severe (n=27, 44.2%) OSAS. The fasting plasma glucose, HbA1c and CRP were measured. Mean age of the patients was 47.7±11.2 years, 72% male. HbA1c, fasting glucose levels show positive correlation with BMI (r=.503, P=.00; r=.258, P=.045). No relation of HbA1c to apnea index nor AHI was detected while positive corelation of fasting glucose and CRP was detected (r=.262, P=.042; r=.258, P=.045). HbA1c, fasting glucose and CRP levels show negative correlation with minimum SpO2 levels (by order of r=-.302, P=.018; r=-.368, P=.004; r=-.365, P=.004). HbA1c, fasting glucose levels and CRP levels show positive correlation with mean desaturation index (time duration in which SpO2<90% by pulse oxymeter) (r=.263, P=.041; r=.311, P=.015; r=.283, P=.027). Although no relation in between increased HbA1c or glucose levels and severity of OSAS was detected in nondiabetic OSAS patients, the correlation with the night hypoxia was detected. This could also show the effect of night time hypoxia on glucose metabolism in OSAS patients. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

Comparative Evaluation of the Antidiabetic Effects of Different Parts of Cassia fistula Linn, a Southeast Asian Plant

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John Wilking Einstein

2013-01-01

Full Text Available The hypoglycemic effect of the methanolic and aqueous extracts of whole parts of Cassia fistula in both normoglycemic and streptozotocin-nictotinamide induced Type 2 diabetic rats were investigated. Acute toxicity, oral glucose tolerance test and glucose uptake in isolated rat hemidiaphragm were performed in normal rats. Diabetes was induced in Sprague Dawley rats by the administration of streptozotocin-nictotinamide (50, 110 mg/kg b.w., resp. intraperitoneally. Different extracts of Cassia was administered to diabetic rats at 250 and 500 mg/kg doses for 21 days. Biochemical parameters like blood glucose, insulin, glycosylated hemoglobin, lipid profile, and serum marker enzymes were determined. The methanolic extract of the bark and leaves were show more effective in causing hypoglycemia in normoglycemic rats. Diabetic rats showed increased levels of glycosylated hemoglobin, reduced levels of plasma insulin, were significantly reverted to near normal after oral administration of the bark and leaf methanolic extracts. Glucose uptake studies in isolated rat hemidiaphragm have shown enhanced peripheral utilization of glucose. Chronic treatment of Cassia remarkably restored the normal status of the histopathological changes observed in the selected tissues. Dose dependent anti-diabetic effects with the cohorts receiving the methanolic extract of bark followed by leaves of Cassia was revealed.

Glucose Pump Test can be Used to Measure Blood Flow Rate of ...

African Journals Online (AJOL)

2018-02-07

Feb 7, 2018 ... Blood flow rates of AV fistula can be affected by osmotic and oncotic pressures of blood and arterial blood pressures. Sodium, glucose, hemoglobin, and albumin are significant effectors, created osmotic and oncotic pressures [Table 3]. Blood levels of hemoglobin. (Hb), albumin, sodium (Na), and glucose ...

Resveratrol, a natural phytoalexin: A therapeutic promise for ...

African Journals Online (AJOL)

into 5 groups: control, control+resveratrol, diabetic, diabetic+resveratrol and diabetic+ glyclazide. The antidiabetic effect of oral administration of. RSV (5mg kg/b.wt) for 45days was evidenced from the improvement in the levels of blood glucose, glycosylated hemoglobin and the calculated homeostasis model assessment of ...

PROFESSIONAL FLASH CONTINUOUS GLUCOSE MONITORING WITH AMBULATORY GLUCOSE PROFILE REPORTING TO SUPPLEMENT A1C: RATIONALE AND PRACTICAL IMPLEMENTATION.

Science.gov (United States)

Hirsch, Irl B; Verderese, Carol A

2017-11-01

Recent consensus statements strongly advocate downloading and interpreting continuous glucose data for diabetes management in patients with type 1 or 2 diabetes. Supplementing periodic glycated hemoglobin (A1C) testing with intermittent continuous glucose monitoring (CGM) using a standardized report form known as the ambulatory glucose profile (AGP) is an evolving standard of care. The rationale for this approach and its implementation with a recently approved novel monitoring technology are explored. Search of the medical literature, professional guidelines, and real-world evidence guided this introduction of an integrative practice framework that uses AGP in conjunction with intermittent flash continuous glucose monitoring (FCGM) as a supplement to A1C testing. The combination of intermittent continuous glucose pattern analysis, standardized glucose metrics, and a readily interpretable data report has the potential to practically extend the recognized benefits of CGM to more patients and clarify the relationship between A1C and average glucose levels in individual cases. Novel FCGM technologies portend greater use of continuous forms of glucose monitoring and wider adoption of AGP report analysis. Additional formal and empirical evidence is needed to more fully characterize best practice. A1C = glycated hemoglobin; AGP = ambulatory glucose profile; CGM = continuous glucose monitoring; FCGM = flash continuous glucose monitoring; IQR = interquartile range; SMBG = self-monitoring of blood glucose.

Trichomonas vaginalis cathepsin D-like aspartic proteinase (Tv-CatD) is positively regulated by glucose and degrades human hemoglobin.

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Mancilla-Olea, Maria Inocente; Ortega-López, Jaime; Figueroa-Angulo, Elisa E; Avila-González, Leticia; Cárdenas-Guerra, Rosa Elena; Miranda-Ozuna, Jesús F T; González-Robles, Arturo; Hernández-García, Mar Saraí; Sánchez-Ayala, Lizbeth; Arroyo, Rossana

2018-04-01

Trichomonas vaginalis genome encodes ∼440 proteases, six of which are aspartic proteases (APs). However, only one belongs to a clan AA (EC 3.4.23.5), family A1 (pepsin A), cathepsin D-like protease. This AP is encoded by an 1113-bp gene (tv-catd), which translates into a 370-aa residues zymogen of 40.7-kDa and a theoretical pI of 4.6, generating a ∼35 kDa active enzyme after maturation (Tv-CatD). The goal of this study was to identify and analyze the effect of glucose on the expression of Tv-CatD at the transcript and protein levels, subcellular localization, and proteolytic activity. The qRT-PCR assays showed a ∼2-fold increase in tv-catd mRNA under high-glucose (HG) conditions compared to glucose-restriction (GR) conditions. We amplified, cloned, and expressed the tv-catd gene, and purified the recombinant precursor enzyme (Tv-CatDr) to generate a polyclonal antibody (anti-Tv-CatDr). Western blot (WB) and immunolocalization assays showed that glucose increases the amount of Tv-CatD in different subcellular localizations and in in vitro secretions. Additionally, Tv-CatD proteolytic activity was detected in protease-resistant extracts (PREs) using a synthetic fluorogenic peptide specific for cathepsin D/E APs at different pHs and in the presence of AP inhibitors. In a two-dimensional (2-DE) WB analysis of a PRE from parasites grown under GR and HG conditions, an anti-Tv-CatDr antibody detected a 35-kDa protein spot at pI 5.0 identified as the mature Tv-CatD form by mass spectrometry that showed proteolytic activity in 2-DE zymograms copolymerized with hemoglobin under both glucose conditions. Thus, Tv-CatD could be involved in trichomonal hemolysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Thermotolerance and protein glycosylation: Inhibition studies with sodium fluoride, azauridine and tunicamycin

International Nuclear Information System (INIS)

Bursey, D.L.; Henle, K.J.; Nagle, W.A.; Moss, A.J.

1987-01-01

The glycosylation hypothesis predicts increased incorporation of monosaccharides into 0-linked glycoproteins during thermotolerance development and inhibition of thermotolerance when this process is blocked. Specific inhibitors of 0-linked glycosylation are not available. The authors examined the effect of non-specific inhibition of glycosylation on thermotolerance development by: 1. restriction of both exogenous sugars and endogeneous sugar synthesis with NaF to block glycolysis while providing L-glutamine as a substrate for ATP synthesis in the TCA cycle; or 2. inhibition of UDP-sugar synthesis using azauridine and tunicamycin. Inhibitors were added to cell cultures after heat conditioning (10 min, 45 0 ) and removed after 6 hr prior to 45 0 -test heating. Sugar deprivation was achieved with 10mM NaF in glucose-free EBSS, supplemented with 2mM L-glutamine. Synthesis of UDP-sugars was inhibited with 1mM azauridine + 1μg/ml tunicamycin. Thermotolerance development was inhibited 87% by NaF/glutamine and 47% by azauridine/tunicamycin. For example, the D/sub o/ of the thermotolerant cells was 42.5 min (control D/sub o/ = 3 min), but only 5.5 min with inhibition by the NaF solution. These results support the absolute requirement of sugar precursors for thermotolerance development as predicted by the glycosylation hypothesis

The relationship between periapical lesions and the serum levels of glycosylated hemoglobin and C-reactive protein in type 2 diabetic patients

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Mohammad S. Al-Zahrani

2017-01-01

Full Text Available Objectives: To investigate the relationship between the presence of periapical lesions (PL and levels of glycosylated hemoglobin (HbA1c, and C-reactive protein (CRP in patients with type 2 diabetes. Methods: This cross-sectional study was conducted at Ibn Sina National College for Medical Studies, Jeddah, Kingdom of Saudi Arabia, between September 2013 and February 2015. Medical and dental history and Sociodemographic data were obtained from participants. Dental and periodontal examinations were conducted and blood samples were obtained to determine levels of HbA1c and CRP. The presence of PL was recorded from panoramic and periapical radiographs. Descriptive statistics and multivariable linear and logistic regression models were used for data analyses. Results: One hundred patients were included; mean age was 48.9 ± 8.5 years. Of these patients, 14% had no PL, whereas 25% had one or 2 lesions, 32% had 3 or 4 lesions, and 29% had ≥5 PL. The mean HbA1c was 9.8% (± 2.5 mg/L and CRP was 6.9 mg/L (± 6.3. The presence of PL was significantly associated with a higher level of HbA1c independent of age, gender, probing depth, and plaque index (p=0.023. Individuals with PL were also more likely to have a high CRP level (>3 mg/L independent of the previous covariates (odds ratio: 1.19; 95% confidence interval: 1.01-1.41. Conclusion: Periapical lesions are associated with a poorer glycemic control and a higher CRP level in type 2 diabetic patients.

Color stabilization of porcine hemoglobin during spray-drying and powder storage by combining chelating and reducing agents.

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Salvador, P; Toldrà, M; Parés, D; Carretero, C; Saguer, E

2009-10-01

This work focuses on the effects of adding a chelating agent - such as nicotinic acid (NA, 2% w/v) or nicotinamide (Nam, 2.5% w/v) - along with glucose as a reducing agent (G, 10% w/v) to fresh porcine hemoglobin in order to stabilize its red color during spray-drying and powder storage at room temperature. Correlations between the CIELAB color parameters and the relative percentages of the different hemoglobin derivatives (liganded and deliganded ferrohemoglobin, and methemoglobin) were analyzed. The results indicate that, although little effects could be observed for any of the combined treatments on fresh hemoglobin, they were effective against pigment autoxidation during dehydration and subsequent storage. From the results, it can also be concluded that glucose was the main contributor to the color stabilization of the hemoglobin powder, probably due to its high water retention capacity.

COMPARATIVE EVALUATION OF HYPOGLYCEMIC EFFECTS OF TWO DIFFERENT PARTS OF BAUHUNIA PURPUREA LINN. PLANT IN STZ-INDUCED DIABETIC ALBINO WISTAR RATS

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A. K. Brahmachari

2015-12-01

Full Text Available The present work was undertaken to study the comparative phytochemical profiles and hypoglycemic effects of Bauhinia purpurea Linn. Barks (BPBE and leaves ethanolic extracts (BPLE in albino wistar rats to validate their ethno medical use in hyperglycemia as well as to explore the better option. Phytochemicals in ethanolic extracts were analyzed by standard natural product chemistry methods. Diabetes was developed in rats by single intraperitoneal injection of Streptozotocin @ 60mg/ Kg bw. Diabetic albino wister rats (n=3 of either sex (150-200gm bw were orally fed with the extracts once daily for 4 weeks. Glibenclamide @ 0.5mg/Kg bw was used as a positive control for comparison. Fasting blood glucose level at 0, 14th and 28th day and hemoglobin and glycosylated hemoglobin on 28th day of experiment were analyzed. Our results show that the extracts contain alkaloids, flavonoids, glycosides, terpenoids, tannins and phenolics. Rats treated with plant extracts show better glucose modulation, decreased hemoglobin glycosylation and improved hemoglobin concentration as compared to diabetic control. The hypoglycemic effect of only BPBE at 420 mgkg-1 on 14th and 28th day is comparable to that of standard drug glibenclamide (P>0.01. The bark extract has been observed to be more potent hypoglycemic agent than leave extract.

1834-IJBCS-Article-Dr Barry Mamoudou Mamoudou+

African Journals Online (AJOL)

hp

of Spirulina on Blood glucose,. Glycosylated Hemoglobin and Lipid. Profile of Male Non-Insulin Dependent. Diabetics. Asian J. Exp. Biol. SCI., 1(1):. 36-46. Branger B, Cadudal JL, Delobel M, Ouoba H,. Yameogo P, Ouedraogo D. 2003. Spiruline as a food supplement in case of infant malnutrition in Burkina-Faso. Arch.

Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

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Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

2015-08-01

Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

Synthesis of Curcumin Glycosides with Enhanced Anticancer Properties Using One-Pot Multienzyme Glycosylation Technique.

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Gurung, Rit Bahadur; Gong, So Youn; Dhakal, Dipesh; Le, Tuoi Thi; Jung, Na Rae; Jung, Hye Jin; Oh, Tae Jin; Sohng, Jae Kyung

2017-09-28

Curcumin is a natural polyphenolic compound, widely acclaimed for its antioxidant, antiinflammatory, antibacterial, and anticancerous properties. However, its use has been limited due to its low-aqueous solubility and poor bioavailability, rapid clearance, and low cellular uptake. In order to assess the effect of glycosylation on the pharmacological properties of curcumin, one-pot multienzyme (OPME) chemoenzymatic glycosylation reactions with UDP- α-D-glucose or UDP-α-D-2-deoxyglucose as donor substrate were employed. The result indicated significant conversion of curcumin to its glycosylated derivatives: curcumin 4'- O -β- glucoside, curcumin 4',4''-di- O -β-glucoside, curcumin 4'- O -β-2-deoxyglucoside, and curcumin 4',4''-di- O -β-2-deoxyglucoside. The products were characterized by ultra-fast performance liquid chromatography, high-resolution quadruple-time-of-flight electrospray ionization-mass spectrometry, and NMR analyses. All the products showed improved water solubility and comparable antibacterial activities. Additionally, the curcumin 4'- O -β-glucoside and curcumin 4'- O -β-2-deoxyglucoside showed enhanced anticancer activities compared with the parent aglycone and diglycoside derivatives. This result indicates that glycosylation can be an effective approach for enhancing the pharmaceutical properties of different natural products, such as curcumin.

Regional variations in frequency of glycosylated hemoglobin (HbA1c) monitoring in Korea: A multilevel analysis of nationwide data.

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Yoo, Kyoung-Hun; Shin, Dong-Wook; Cho, Mi-Hee; Kim, Sang-Hyuck; Bahk, Hyun-Jung; Kim, Shin-Hye; Jeong, Su-Min; Yun, Jae-Moon; Park, Jin-Ho; Kim, Heesun; Cho, BeLong

2017-09-01

Suboptimal frequency of glycosylated hemoglobin (HbA1c) monitoring is associated with poor diabetes control. We aimed to analyze compliance to HbA1c testing guidelines and explore associated individual and area-level determinants, focusing on regional variation. This cross-sectional study between the period of 2012-2013 was conducted by using the Korean National Health Insurance Research Database, and included 45,634 patients diagnosed with diabetes mellitus, who were prescribed any anti-diabetic medications, including insulin. We calculated the proportion of each HbA1c testing frequency (≥1, ≥2, or ≥4 times per year) stratified by 17 administrative regions. Multilevel and multivariate logistic analyses were performed with regional (proportion of farmer population) and individual characteristics (age, sex, income level, duration of diabetes, and most visited medical institution). Overall, 67.3% of the patients received≥1 HbA1c test per year; 37.8% and 6.1% received ≥2 and ≥4 tests per year, respectively. Those managed in secondary-level hospitals or clinics and those living in rural areas were less likely to receive HbA1c testing. Even after adjusting for individual and regional level characteristics, significant area level variation was observed (variance participant coefficients were 7.91%, 9.58%, and 14.43% for testing frequencies of ≥1, ≥2, and ≥4 times a year, respectively). The frequency of HbA1c monitoring is suboptimal in Korea, especially in rural areas. Moreover, significant regional variation was observed, implying a contextual effect. This suggests the need for developing policy actions to improve HbA1c monitoring. In particular, access to HbA1c testing in rural primary care clinics must be improved. Copyright © 2017 Elsevier B.V. All rights reserved.

The relationship between periapical lesions and the serum levels of glycosylated hemoglobin and C-reactive protein in type 2 diabetic patients.

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Al-Zahrani, Mohammad S; Abozor, Basel M; Zawawi, Khalid H

2017-01-01

To investigate the relationship between the presence of periapical lesions (PL) and levels of glycosylated hemoglobin (HbA1c), and C-reactive protein (CRP) in patients with type 2 diabetes.  Methods: This cross-sectional study was conducted at Ibn Sina National College for Medical Studies, Jeddah, Kingdom of Saudi Arabia, between September 2013 and February 2015. Medical and dental history and Sociodemographic data were obtained from participants. Dental and periodontal examinations were conducted and blood samples were obtained to determine levels of HbA1c and CRP. The presence of PL was recorded from panoramic and periapical radiographs. Descriptive statistics and multivariable linear and logistic regression models were used for data analyses.  Results: One hundred patients were included; mean age was 48.9 ± 8.5 years. Of these patients, 14% had no PL, whereas 25% had one or 2 lesions, 32% had 3 or 4 lesions, and 29% had ≥5 PL. The mean HbA1c was 9.8% (± 2.5) mg/L and CRP was 6.9 mg/L (± 6.3). The presence of PL was significantly associated with a higher level of HbA1c independent of age, gender, probing depth, and plaque index (p=0.023). Individuals with PL were also more likely to have a high CRP level (greater than 3 mg/L) independent of the previous covariates (odds ratio: 1.19; 95% confidence interval: 1.01-1.41).  Conclusion: Periapical lesions are associated with a poorer glycemic control and a higher CRP level in type 2 diabetic patients.

Functional importance of PAI-1 glycosylation

DEFF Research Database (Denmark)

Christensen, Anni; Naessens, Dominik; Skottrup, Peter

2001-01-01

Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-glycosylated PAI-1 could be conferred upon PAI-1 expressed in HEK293 cells by mutational inactivation of one or the other glycosylation site. These findings reveal a novel functional role for glycosylation of a serpin. The glycosylation sites are localised between a-helix H and b-strand 2C and b-strand 3C and a...

Pediatric metabolic outcome comparisons based on a spectrum of obesity and asthmatic symptoms.

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Perdue, Ashley D; Cottrell, Lesley A; Lilly, Christa L; Gower, William A; Ely, Brian A; Foringer, Brad; Wright, Melvin L; Neal, William A

2018-04-20

Asthma and obesity are two of the most prevalent public health issues for children in the U.S. Trajectories of both have roughly paralleled one another over the past several decades causing many to explore their connection to one another and to other associated health issues such as diabetes and dyslipidemia. Earlier models have commonly designated obesity as the central hub of these associations; however, more recent models have argued connections between pediatric asthma and other obesity-related metabolic conditions regardless of children's obesity risk. To examine the relationships between asthma, obesity, and abnormal metabolic indices. We conducted a cross-sectional study of 179 children ages 7 to 12 years recruited from a rural, Appalachian region. Our model controlled for children's smoke exposure, body mass index percentile, and gender to examine the association between children's asthma (based on pulmonary function tests, medical history, medications, and parent report of severity), lipids (fasting lipid profile), and measures of altered glucose metabolism (glycosylated hemoglobin and homeostatic model assessment 2-insulin resistance). Our findings revealed a statistically significant model for low density lipids, high density lipids, log triglyceride, and homeostatic model assessment 2-insulin resistance; however, a statistically significant main effect for asthma was found for triglycerides. We also found an asthma-obesity interaction effect on children's glycosylated hemoglobin with asthmatic obese children revealing significantly higher glycosylated hemoglobin values than non-asthmatic obese children. Our findings support a connection between asthma and children's glycosylated hemoglobin values; however, this association remains entwined with obesity factors.

Study on the relationship between blood levels of glycated hemoglobin (HbA1c) and micro-vascular nephropathy in patients with type 2 diabetes

International Nuclear Information System (INIS)

Luo Rong; Li Zhuocheng; Yan Dewen

2004-01-01

Objective: To evaluate the relationship between blood levels of glycated hemoglobin and microvascular nephropathy in patients with type diabetes. Methods: Blood Glycosylated hemoglobin levels were determined with affinity chromatography and 24 hour urinary microalbumin (m-Alb), β 2 microglobin (β 2 -m) quantified with RIA in 76 patients and 30 controls. Results: With glycated hemoglobin within normal range, there were no differences between the amounts of patients' urinary protein contents and those in controls (P>0.05). With higher blood glycated hemoglobin levels, significant differences could be observed (P 2 microglobin. Differences among the 24 hour urinary quantities of mAlb and β 2 -m in the three groups of patients (divided according to the HbA1c levels, namely 9.0%) were also significant (P 2 microglobin is very important for early detection of diabetic nephropathy

Effect of chromium supplementation on glycated hemoglobin and fasting plasma glucose in patients with diabetes mellitus.

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Yin, Raynold V; Phung, Olivia J

2015-02-13

Chromium (Cr) is a trace element involved in glucose homeostasis. We aim to evaluate and quantify the effects of Cr supplementation on A1C and FPG in patients with T2DM. A systematic literature search of Pubmed, EMBASE and the Cochrane Library (from database inception to 11/2014) with no language restrictions sought RCTs or cohort studies evaluating Cr supplementation in T2DM vs control and reporting either change in glycated hemoglobin (A1C) or fasting plasma glucose (FPG). Meta-analysis was conducted on each subtype of Cr supplement separately, and was analyzed by random effects model to yield the weighted mean differences (WMD) and 95% confidence intervals (CIs). Heterogeneity was assessed by using the I(2) statistic. A total of 14 RCTs (n=875 participants, mean age range: 30 to 83 years old, 8 to 24 weeks of follow-up) were identified (Cr chloride: n=3 study, Cr picolinate: n=5 study, brewer's yeast: n=4 study and Cr yeast: n=3 study). Compared with placebo, Cr yeast, brewer's yeast and Cr picolinate did not show statistically significant effects on A1C. Furthermore, compared to control, Cr chloride, Cr yeast and Cr picolinate showed no effect on FPG, however, brewer's yeast showed a statistically significant decrease in FPG -19.23 mg/dL (95% CI=-35.30 to -3.16, I(2)=21%, n=137). Cr supplementation with brewer's yeast may provide marginal benefits in lowering FPG in patients with T2DM compared to placebo however it did not have any effect on A1C.

The association between estimated average glucose levels and fasting plasma glucose levels in a rural tertiary care centre

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Raja Reddy P

2013-01-01

Full Text Available The level of hemoglobin A1c (HbA1c, also known as glycated hemoglobin, determines how well a patient’s blood glucose level has been controlled over the previous 8-12 weeks. HbA1c levels help patients and doctors understand whether a particular diabetes treatment is working and whether adjustments need to be made to the treatment. Because the HbA1c level is a marker of blood glucose for the previous 60- 90 days, average blood glucose levels can be estimated using HbA1c levels. Aim in the present study was to investigate the relationship between estimated average glucose levels, as calculated by HbA1c levels, and fasting plasma glucose levels. Methods: Type 2 diabetes patients attending medicine outpatient department of RL Jalappa hospital, Kolar between March 2010 and July 2012 were taken. The estimated glucose levels (mg/dl were calculated using the following formula: 28.7 x HbA1c-46.7. Glucose levels were determined using the hexokinase method. HbA1c levels were determined using an HPLC method. Correlation and independent t- test was the test of significance for quantitative data. Results: A strong positive correlation between fasting plasma glucose level and estimated average blood glucose levels (r=0.54, p=0.0001 was observed. The difference was statistically significant. Conclusion: Reporting the estimated average glucose level together with the HbA1c level is believed to assist patients and doctors determine the effectiveness of blood glucose control measures.

The effects of mindfulness eating and yoga exercise on blood sugar levels of pregnant women with gestational diabetes mellitus.

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Youngwanichsetha, Sununta; Phumdoung, Sasitorn; Ingkathawornwong, Thitiporn

2014-11-01

This randomized controlled trial was carried out to investigate the effect of mindfulness eating and yoga exercise on blood sugar levels among pregnant Thai women with GDM. Interventions promoting achievement of good glycemic control result in desired pregnancy outcomes. Little is known about the health benefits of mindfulness eating and yoga exercise on blood sugar levels among pregnant with GDM. A randomized controlled trial was carried out. Main outcome measures were capillary fasting plasma glucose, 2-h postprandial blood glucose, and hemoglobin A1c. The intervention group showed significantly reduced fasting plasma glucose, 2-h postprandial blood glucose, and glycosylated hemoglobin (HbA1c) in the intervention group (pMindfulness eating and yoga exercise had health benefits on glycemic control in pregnant women with GDM. It should be recommended in clinical and community health services. Copyright © 2014 Elsevier Inc. All rights reserved.

Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date

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Cinti F

2017-10-01

Full Text Available Francesca Cinti,* Simona Moffa,* Flavia Impronta,* Chiara MA Cefalo, Vinsin A Sun, Gian Pio Sorice, Teresa Mezza, Andrea Giaccari Center for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario A Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy *These authors contributed equally to this work Abstract: Sodium-glucose cotransporter 2 (SGLT2 inhibitors are the latest therapeutic strategy in the treatment of type 2 diabetes mellitus (T2DM. Using an insulin-independent mechanism (glycosuria, they reduce glucose toxicity and improve insulin sensitivity and β-cell function. The promising results obtained in clinical trials show that SGLT2 significantly improves glycemic control and provides greater cardiovascular protection, combined with a reduction in body weight and blood pressure (BP. This review focuses on ertugliflozin, a new, highly selective, and reversible SGLT2 inhibitor. Clinical trials published to date show that ertugliflozin, both as a monotherapy and as an add-on to oral antidiabetic agents, is safe and effective in reducing glycosylated hemoglobin (HbA1c, body weight, and BP in T2DM patients. Keywords: antidiabetic drugs, glycosylated hemoglobin, glycemic control, sodium-glucose cotransporter 2 inhibitors, precision medicine, type 1 diabetes mellitus, type 2 diabetes mellitus, weight reduction 

Clinical coaching in primary care: Capable of improving control in patients with type 2 diabetes mellitus?

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González-Guajardo, Eduardo Enrique; Salinas-Martínez, Ana María; Botello-García, Antonio; Mathiew-Quiros, Álvaro

2016-06-01

Few clinical coaching studies are both endorsed by real cases and focused on reducing suboptimal diabetes control. We evaluated the effectiveness of coaching on improving type 2 diabetes goals after 3 years of implementation in primary care. A cross-sectional study with follow up was conducted during 2008-2011. Coaching consisted of guiding family doctors to improve their clinical abilities, and it was conducted by a medical doctor trained in skill building, experiential learning, and goal setting. Effectiveness was assessed by means of fasting plasma glucose and glycosylated hemoglobin outcomes. The main analysis consisted of 1×3 and 2×3 repeated measures ANOVAs. A significant coaching×time interaction was observed, indicating that the difference in glucose between primary care units with and without coaching increased over time (Wilks' lambda multivariate test, PCoaching increased 1.4 times (95%CI 1.3, 1.5) the possibility of reaching the fasting glucose goal after controlling for baseline values. There was also a significant improvement in glycosylated hemoglobin (Bonferroni-corrected p-value for pairwise comparisons, Pcoaching was found to be worth the effort to improve type 2 diabetes control in primary care. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Characterization of different FAD-dependent glucose dehydrogenases for possible use in glucose-based biosensors and biofuel cells.

Science.gov (United States)

Zafar, Muhammad Nadeem; Beden, Najat; Leech, Dónal; Sygmund, Christoph; Ludwig, Roland; Gorton, Lo

2012-02-01

In this study, different flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenases (FADGDHs) were characterized electrochemically after "wiring" them with an osmium redox polymer [Os(4,4'-dimethyl-2,2'-bipyridine)(2)(PVI)(10)Cl](+) on graphite electrodes. One tested FADGDH was that recently discovered in Glomerella cingulata (GcGDH), another was the recombinant form expressed in Pichia pastoris (rGcGDH), and the third was a commercially available glycosylated enzyme from Aspergillus sp. (AspGDH). The performance of the Os-polymer "wired" GDHs on graphite electrodes was tested with glucose as the substrate. Optimal operational conditions and analytical characteristics like sensitivity, linear ranges and current density of the different FADGDHs were determined. The performance of all three types of FADGDHs was studied at physiological conditions (pH 7.4). The current densities measured at a 20 mM glucose concentration were 494 ± 17, 370 ± 24, and 389 ± 19 μA cm(-2) for GcGDH, rGcGDH, and AspGDH, respectively. The sensitivities towards glucose were 2.16, 1.90, and 1.42 μA mM(-1) for GcGDH, rGcGDH, and AspGDH, respectively. Additionally, deglycosylated rGcGDH (dgrGcGDH) was investigated to see whether the reduced glycosylation would have an effect, e.g., a higher current density, which was indeed found. GcGDH/Os-polymer modified electrodes were also used and investigated for their selectivity for a number of different sugars.

Control of mucin-type O-glycosylation

DEFF Research Database (Denmark)

Bennett, Eric P; Mandel, Ulla; Clausen, Henrik

2012-01-01

residues, is one of the most abundant forms of protein glycosylation in animals. Although most protein glycosylation is controlled by one or two genes encoding the enzymes responsible for the initiation of glycosylation, i.e. the step where the first glycan is attached to the relevant amino acid residue...... in the protein, mucin-type O-glycosylation is controlled by a large family of up to 20 homologous genes encoding UDP-GalNAc:polypeptide GalNAc-transferases (GalNAc-Ts) (EC 2.4.1.41). Therefore, mucin-type O-glycosylation has the greatest potential for differential regulation in cells and tissues. The Gal...

N- and O-glycosylation Analysis of Human C1-inhibitor Reveals Extensive Mucin-type O-Glycosylation.

Science.gov (United States)

Stavenhagen, Kathrin; Kayili, H Mehmet; Holst, Stephanie; Koeleman, Carolien A M; Engel, Ruchira; Wouters, Diana; Zeerleder, Sacha; Salih, Bekir; Wuhrer, Manfred

2018-06-01

Human C1-inhibitor (C1-Inh) is a serine protease inhibitor and the major regulator of the contact activation pathway as well as the classical and lectin complement pathways. It is known to be a highly glycosylated plasma glycoprotein. However, both the structural features and biological role of C1-Inh glycosylation are largely unknown. Here, we performed for the first time an in-depth site-specific N - and O -glycosylation analysis of C1-Inh combining various mass spectrometric approaches, including C18-porous graphitized carbon (PGC)-LC-ESI-QTOF-MS/MS applying stepping-energy collision-induced dissociation (CID) and electron-transfer dissociation (ETD). Various proteases were applied, partly in combination with PNGase F and exoglycosidase treatment, in order to analyze the (glyco)peptides. The analysis revealed an extensively O -glycosylated N-terminal region. Five novel and five known O -glycosylation sites were identified, carrying mainly core1-type O -glycans. In addition, we detected a heavily O -glycosylated portion spanning from Thr 82 -Ser 121 with up to 16 O -glycans attached. Likewise, all known six N -glycosylation sites were covered and confirmed by this site-specific glycosylation analysis. The glycoforms were in accordance with results on released N -glycans by MALDI-TOF/TOF-MS/MS. The comprehensive characterization of C1-Inh glycosylation described in this study will form the basis for further functional studies on the role of these glycan modifications. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Moderate glucose supply reduces hemolysis during systemic inflammation

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Jägers J

2018-03-01

Full Text Available Johannes Jägers,1 Stephan Brauckmann,2 Michael Kirsch,1 Katharina Effenberger-Neidnicht1,3 1Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany; 2Clinic for Anesthesiology and Intensive Care, University Hospital Essen, Essen, Germany; 3Institute of Physiological Chemistry, University Hospital Essen, Essen, Germany Background: Systemic inflammation alters energy metabolism. A sufficient glucose level, however, is most important for erythrocytes, since erythrocytes rely on glucose as sole source of energy. Damage to erythrocytes leads to hemolysis. Both disorders of glucose metabolism and hemolysis are associated with an increased risk of death. The objective of the study was to investigate the impact of intravenous glucose on hemolysis during systemic inflammation.Materials and methods: Systemic inflammation was accomplished in male Wistar rats by continuous lipopolysaccharide (LPS infusion (1 mg LPS/kg and h, 300 min. Sham control group rats received Ringer’s solution. Glucose was supplied moderately (70 mg glucose/kg and h or excessively (210 mg glucose/kg and h during systemic inflammation. Vital parameters (eg, systemic blood pressure as well as blood and plasma parameters (eg, concentrations of glucose, lactate and cell-free hemoglobin, and activity of lactate dehydrogenase were measured hourly. Clot formation was analyzed by thromboelastometry.Results: Continuous infusion of LPS led to a so-called post-aggression syndrome with disturbed electrolyte homeostasis (hypocalcemia, hyperkalemia, and hypernatremia, changes in hemodynamics (tachycardia and hypertension, and a catabolic metabolism (early hyperglycemia, late hypoglycemia, and lactate formation. It induced severe tissue injury (significant increases in plasma concentrations of transaminases and lactate dehydrogenase, alterations in blood coagulation (disturbed clot formation, and massive hemolysis. Both moderate and excessive glucose supply reduced LPS

Prediction of glycosylation sites using random forests

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Hirst Jonathan D

2008-11-01

Full Text Available Abstract Background Post translational modifications (PTMs occur in the vast majority of proteins and are essential for function. Prediction of the sequence location of PTMs enhances the functional characterisation of proteins. Glycosylation is one type of PTM, and is implicated in protein folding, transport and function. Results We use the random forest algorithm and pairwise patterns to predict glycosylation sites. We identify pairwise patterns surrounding glycosylation sites and use an odds ratio to weight their propensity of association with modified residues. Our prediction program, GPP (glycosylation prediction program, predicts glycosylation sites with an accuracy of 90.8% for Ser sites, 92.0% for Thr sites and 92.8% for Asn sites. This is significantly better than current glycosylation predictors. We use the trepan algorithm to extract a set of comprehensible rules from GPP, which provide biological insight into all three major glycosylation types. Conclusion We have created an accurate predictor of glycosylation sites and used this to extract comprehensible rules about the glycosylation process. GPP is available online at http://comp.chem.nottingham.ac.uk/glyco/.

Hallmarks of glycosylation in cancer.

Science.gov (United States)

Munkley, Jennifer; Elliott, David J

2016-06-07

Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a 'hallmark of cancer' but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark.

Reduction of Fasting Blood Glucose and Hemoglobin A1c Using Oral Aloe Vera: A Meta-Analysis.

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Dick, William R; Fletcher, Emily A; Shah, Sachin A

2016-06-01

Diabetes mellitus is a global epidemic and one of the leading causes of morbidity and mortality. Additional medications that are novel, affordable, and efficacious are needed to treat this rampant disease. This meta-analysis was performed to ascertain the effectiveness of oral aloe vera consumption on the reduction of fasting blood glucose (FBG) and hemoglobin A1c (HbA1c). PubMed, CINAHL, Natural Medicines Comprehensive Database, and Natural Standard databases were searched. Studies of aloe vera's effect on FBG, HbA1c, homeostasis model assessment-estimated insulin resistance (HOMA-IR), fasting serum insulin, fructosamine, and oral glucose tolerance test (OGTT) in prediabetic and diabetic populations were examined. After data extraction, the parameters of FBG and HbA1c had appropriate data for meta-analyses. Extracted data were verified and then analyzed by StatsDirect Statistical Software. Reductions of FBG and HbA1c were reported as the weighted mean differences from baseline, calculated by a random-effects model with 95% confidence intervals. Subgroup analyses to determine clinical and statistical heterogeneity were also performed. Publication bias was assessed by using the Egger bias statistic. Nine studies were included in the FBG parameter (n = 283); 5 of these studies included HbA1c data (n = 89). Aloe vera decreased FBG by 46.6 mg/dL (p aloe vera for significantly reducing FBG (46.6 mg/dL) and HbA1c (1.05%). Further clinical studies that are more robust and better controlled are warranted to further explore these findings.

Impact of Mean Cell Hemoglobin on Hb A1c-Defined Glycemia Status.

Science.gov (United States)

Rodriguez-Segade, Santiago; Garcia, Javier Rodriguez; García-López, José M; Gude, Francisco; Casanueva, Felipe F; Rs-Alonso, Santiago; Camiña, Félix

2016-12-01

Several hematological alterations are associated with altered hemoglobin A 1c (Hb A 1c ). However, there have been no reports of their influence on the rates of exceeding standard Hb A 1c thresholds by patients for whom Hb A 1c determination is requested in clinical practice. The initial data set included the first profiles (complete blood counts, Hb A 1c , fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A 1c . Fasting glucose, MCH, and age emerged as predictors of Hb A 1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A 1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (≤27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A 1c , a 1 pg increase in MCH reduced the odds of Hb A 1c -defined dysglycemia, diabetes and poor glycemia control by 10%-14%. For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A 1c -based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A 1c levels in clinical practice. © 2016 American Association for Clinical Chemistry.

Diabetes-induced increases in 131I-albumin permeation are unaffected by essential fatty acid depletion

International Nuclear Information System (INIS)

Williamson, J.R.; Lefkowith, J.B.; Chang, K.; Tilton, R.G.

1990-01-01

The authors assessed effects of essential fatty acid deficiency (EFAD) on regional 131 I-albumin permeation in diabetic and age-matched control rats. Male, Sprague-Dawley rats (50-75 g) were randomized into EFAD diet or normal diet groups. Three months later, diabetes was induced in one half of the rats in each group by injecting i.v. 35-45 mg/kg b.w. streptozotocin. One month later, 131 I-albumin clearance (μ g plasma/g tissue/minute) was assessed as described previously (Circ Res 64;890, 1989). Within controls, EFAD decreased body weight gain 28% but did not affect control values for plasma glucose (118±8 (SD) mg/dl) or glycosylated hemoglobin (1.33±0.22 % of total hemoglobin). In normal diet and EFAD diabetics, plasma glucose (535±64 and 419±161, respectively) and glycosylated hemoglobin (4.38±0.97 and 2.97±1.69) were increased significantly versus controls. Diabetes increased 131 I-albumin clearance in retinal (5.1x controls), choroid (3.4x), anterior uvea (2.7x), aorta (3.5x), and sciatic nerve (2.2x). No differences were evident in tissue 131 I-albumin clearances between both control groups or both diabetic groups. These results suggest that essential fatty acids do not modulate diabetes-induced changes in endothelial cell barrier function

Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2 inhibitor for the treatment of type 2 diabetes

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Joshua J Neumiller

2014-06-01

Full Text Available Type 2 diabetes is increasing in prevalence worldwide, and hyperglycemia is often poorly controlled despite a number of therapeutic options. Unlike previously available agents, sodium-glucose co-transporter 2 (SGLT2 inhibitors offer an insulin-independent mechanism for improving blood glucose levels, since they promote urinary glucose excretion (UGE by inhibiting glucose reabsorption in the kidney. In addition to glucose control, SGLT2 inhibitors are associated with weight loss and blood pressure reductions, and do not increase the risk of hypoglycemia. Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with up to 90 g of glucose excreted per day. It can be administered orally, and studies of people with renal or hepatic impairment indicated empagliflozin needed no dose adjustment based on pharmacokinetics. In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure. As add-on to basal insulin, empagliflozin not only improved HbA1c levels but also reduced insulin doses. Across studies, empagliflozin was generally well tolerated with a similar rate of hypoglycemia to placebo; however, patients had a slightly increased frequency of genital infections, but not urinary tract infections, versus placebo. Phase III studies have also reported a good safety profile along with significant improvements in HbA1c, weight and blood pressure, with no increased risk of hypoglycemia versus placebo. Based on available data, it appears that empagliflozin may be a useful option in a range of patients; however, clinical decisions will be better informed by the results of ongoing studies, in particular, a large cardiovascular outcome study (EMPA-REG OUTCOME™.

Regulation of hemoglobin AIc formation in human erythrocytes in vitro. Effects of physiologic factors other than glucose.

OpenAIRE

Smith, R J; Koenig, R J; Binnerts, A; Soeldner, J S; Aoki, T T

1982-01-01

The formation of hemoglobin AIc was studied in intact human erythrocytes in vitro. Satisfactory methods were developed for maintaining erythrocytes under physiologic conditions for greater than 8 d with less than 10% hemolysis. Hemoglobin AIc levels were determined chromatographically on erythrocyte hemolysates after removal of reversible components by incubation for 6 h at 37 degree C. Hemoglobin AIc concentration was found to increase linearly with time during 8 d of incubation. The rate of...

Characterization of different FAD-dependent glucose dehydrogenases for possible use in glucose-based biosensors and biofuel cells

Energy Technology Data Exchange (ETDEWEB)

Zafar, Muhammad Nadeem; Beden, Najat; Gorton, Lo [Lund University, Department of Biochemistry and Structural Biology, Lund (Sweden); Leech, Donal [National University of Ireland Galway, School of Chemistry, Galway (Ireland); Sygmund, Christoph; Ludwig, Roland [BOKU-University of Natural Resources and Life Sciences Vienna, Food Biotechnology Laboratory, Department of Food Sciences and Technology, Wien (Austria)

2012-02-15

In this study, different flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenases (FADGDHs) were characterized electrochemically after ''wiring'' them with an osmium redox polymer [Os(4,4'-dimethyl-2,2'-bipyridine){sub 2}(PVI){sub 10}Cl]{sup +} on graphite electrodes. One tested FADGDH was that recently discovered in Glomerella cingulata (GcGDH), another was the recombinant form expressed in Pichia pastoris (rGcGDH), and the third was a commercially available glycosylated enzyme from Aspergillus sp. (AspGDH). The performance of the Os-polymer ''wired'' GDHs on graphite electrodes was tested with glucose as the substrate. Optimal operational conditions and analytical characteristics like sensitivity, linear ranges and current density of the different FADGDHs were determined. The performance of all three types of FADGDHs was studied at physiological conditions (pH 7.4). The current densities measured at a 20 mM glucose concentration were 494 {+-} 17, 370 {+-} 24, and 389 {+-} 19 {mu}A cm{sup -2} for GcGDH, rGcGDH, and AspGDH, respectively. The sensitivities towards glucose were 2.16, 1.90, and 1.42 {mu}A mM{sup -1} for GcGDH, rGcGDH, and AspGDH, respectively. Additionally, deglycosylated rGcGDH (dgrGcGDH) was investigated to see whether the reduced glycosylation would have an effect, e.g., a higher current density, which was indeed found. GcGDH/Os-polymer modified electrodes were also used and investigated for their selectivity for a number of different sugars. (orig.)

Effectiveness of a behavior modification program for older people with uncontrolled type 2 diabetes.

Science.gov (United States)

Ounnapiruk, Liwan; Wirojratana, Virapun; Meehatchai, Nitaya; Turale, Sue

2014-06-01

This quasi-experimental study examined the effectiveness of a behavior modification program for diabetic control in Thai elders with uncontrolled Type 2 Diabetes. Purposive sampling was used to select 30 elders from one community as an intervention group, and 30 from a neighboring community as a control group. The intervention group participated in a program of 12 weeks' duration involving activities related to group counseling, group discussion, and an empowerment process that enhanced appropriate consumption of healthy diet, medication taking, and exercise. Data were collected by interviews using a questionnaire to assess knowledge of diabetes, perceived self-efficacy, and diabetes control behavior, including fasting blood glucose and glycosylated hemoglobin, were examined at the baseline and three months thereafter. At program completion, the intervention group had significantly higher scores of knowledge, self-efficacy, and health behaviors than those in the control group, but blood glucose and glycosylated hemoglobin were not significantly different. Although nurses can use aspects of this program to benefit elders with diabetes who require support and education, further research is required to provide improved health outcomes such as better glycemic control. © 2013 Wiley Publishing Asia Pty Ltd.

Effect of mufa enriched extra virgin olive oil on glycemic status and insulin secretion in diabetic rats

International Nuclear Information System (INIS)

Naveed, A.K.; Yousaf, M.J.; Khan, S.; Ahmed, T.; Azeem, Z.

2013-01-01

Objective: To evaluate the effect of monounsaturated fatty acid enriched extra virgin olive oil on glycemic status and insulin secretion in diabetic rats. Study Design: Randomized Control Trial. Place and Duration of Study: Department of Biochemistry, Army Medical College, Rawalpindi in collaboration with Centre for Research in Experimental and Applied Medicine, Army Medical College, Rawalpindi and National Institute of Health, Islamabad from March 2010 to June 2011. Material and Methods: Eighty albino rats of Sprague-dawley strain weighing 200-250 g were randomly divided into two groups of 40 rats each. Rats were made diabetic by injecting streptozotocin. Group 1 and Group II were given normal rodent diet and extra virgin olive oil supplemented diet respectively for 06 weeks. At the end of experimentation, fasting blood glucose, glycosylated hemoglobin and insulin were measured. Results: There was significant decrease of fasting blood glucose and glycosylated hemoglobin and significant increase of serum insulin of group II rats when it was compared with group I (control). Conclusion: Monounsaturated fatty acids enriched extra virgin olive oil can significantly improve glycemic status and serum insulin in diabetic rats. (author)

Blood glucose self-monitoring patterns in Mexican Americans: further lessons from the Starr County Border Health Initiative.

Science.gov (United States)

Cuevas, Heather E; Brown, Sharon A; García, Alexandra A; Winter, Mary; Brown, Adama; Hanis, Craig L

2015-02-01

The purpose was to describe patterns of home self-monitoring of blood glucose (SMBG) in Mexican Americans with type 2 diabetes mellitus enrolled in a diabetes self-management education protocol. Research questions were as follows: (1) What were the patterns and rates of home glucose self-monitoring over the 6-month course of the study? (2) What were the differences in monitoring rates between experimental and control groups? (3) What were the relationships between rates of monitoring and glycosylated hemoglobin (A1C), gender, and years with diabetes? We used a randomized (by group) repeated-measures pretest/posttest control group design. Glucometer data from an experimental group (diabetes self-management education plus nurse case management) and a comparison group (diabetes self-management education only) were analyzed. Data were collected at baseline and at 3 and 6 months. Overall average SMBG rates were low. Experimental and control group monitoring levels were not significantly different. More females than males never monitored glucose values, but more females than males checked at least one time per week. Those participants who checked their glucose levels more than once per week had diabetes for a longer period of time. Rates of monitoring were not strongly associated with A1C levels at 3 and 6 months, but at 6 months A1C levels were statistically significantly different based on whether or not individuals monitored their glucose levels (P=0.03, n=71). SMBG rates were low in this study despite SMBG education and access to free glucometers and test strips. The lower rates of SMBG may reflect the effects of unexpected environmental challenges, but exact causes remain unclear. Reasons for low rates of SMBG need to be explored further, especially in underserved communities.

Functional importance of PAI-1 glycosylation

DEFF Research Database (Denmark)

Christensen, Anni; Naessens, Dominik; Skottrup, Peter

susceptible PAI-1 variant was not necessarily the one used when raising the antibody. This and other observations indicated that the carbohydrate moieties or the glycosylation sites are unlikely to be part of the epitopes for these antibodies. The antibody susceptibility characteristic for non......Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-linked glycosylation. Biochemical analysis of PAI-1 variants with substitutions of the Asn residues in each of these sites and expression in human embryonic kidney 293 (HEK293) cells showed that only Asn211 and Asn 267, but not Asn331 are glycosylated, and revealed a differential composition of the carbohydrate...

A1C as a diagnostic criteria for diabetes in low- and middle-income settings: evidence from Peru.

OpenAIRE

J Jaime Miranda; Antonio Bernabe-Ortiz; Sanja Stanojevic; German Malaga; Robert H Gilman; Liam Smeeth

2011-01-01

Objectives To determine the prevalence of type 2 diabetes mellitus, in three groups of Peruvian adults, using fasting glucose and glycosylated hemoglobin (A1C). Methodology/Principal Findings This study included adults from the PERU MIGRANT Study who had fasted ≥8 h. Fasting glucose ≥126 mg/dL and A1C≥6.5% were used, separately, to define diabetes. Subjects with a current diagnosis of diabetes were excluded. 964 of 988 subjects were included in this analysis. Overall, 0.9% (95%CI 0.3–1.5) and...

HBA1C AND MEAN GLUCOSE DERIVED FROM SHORT-TERM CONTINUOUS GLUCOSE MONITORING ASSESSMENT DO NOT CORRELATE IN PATIENTS WITH HBA1C >8.

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Yamada, Eijiro; Okada, Shuichi; Nakajima, Yasuyo; Bastie, Claire C; Vatish, Manu; Tagaya, Yuko; Osaki, Aya; Shimoda, Yoko; Shibusawa, Ryo; Saito, Tsugumichi; Okamura, Takashi; Ozawa, Atsushi; Yamada, Masanobu

2017-01-01

Optimum therapy for patients with diabetes depends on both acute and long-term changes in plasma glucose, generally assessed by glycated hemoglobin (HbA1c) levels. However, the correlation between HbA1c and circulating glucose has not been fully determined. Therefore, we carefully examined this correlation when glucose levels were assessed by continuous glucose monitoring (CGM). Fifty-one patients (70% female, 30% male) were examined; among them were 28 with type 1 diabetes and 23 with type 2 diabetes. Clinically determined HbA1c levels were compared with blood glucose determined by CGM during a short time period. Changes in HbA1c levels up to 8.0% showed a clear and statistically strong correlation (R = 0.6713; PHbA1c and CGM-assessed glucose levels in our patient population when HbA1c was >8.0%. Short-term CGM appears to be a good clinical indicator of long-term glucose control (HbA1c levels); however, cautions should be taken while interpreting CGM data from patients with HbA1c levels >8.0%. Over- or underestimation of the actual mean glucose from CGM data could potentially increase the risks of inappropriate treatment. As such, our results indicate that a more accurate analysis of CGM data might be useful to adequately tailor clinical treatments. ADAG = A1c-Derived Average Glucose CGM = continuous glucose monitoring %CV = percent coefficient of variation HbA1c = glycated hemoglobin.

The Added Value of Oral Glucose Tolerance Testing in Pre-Diabetes

NARCIS (Netherlands)

Luijf, Yoeri M.; Hermanides, Jeroen; Serlie, Mireille J.; Hoekstra, Joost B.; Soeters, Maarten R.

2011-01-01

With the increased acceptance of glycated hemoglobin measurement as the test of choice for the diagnosis and detection of diabetes, doubts which surround the use of the oral glucose tolerance test (OGTT) in detecting disturbances in glucose levels have become even more apparent. Metabolically, there

Treatment with the dipeptidyl peptidase-4 inhibitor vildagliptin improves fasting islet-cell function in subjects with type 2 diabetes.

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D'Alessio, David A; Denney, Amanda M; Hermiller, Linda M; Prigeon, Ronald L; Martin, Julie M; Tharp, William G; Saylan, Monica Liqueros; He, Yanling; Dunning, Beth E; Foley, James E; Pratley, Richard E

2009-01-01

Dipeptidyl peptidase 4 (DPP-4) inhibitors are proposed to lower blood glucose in type 2 diabetes mellitus (T2DM) by prolonging the activity of the circulating incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). Consistent with this mechanism of action, DPP-4 inhibitors improve glucose tolerance after meals by increasing insulin and reducing glucagon levels in the plasma. However, DPP-4 inhibitors also reduce fasting blood glucose, an unexpected effect because circulating levels of active GIP and GLP-1 are low in the postabsorptive state. The objective of the study was to examine the effects of DPP-4 inhibition on fasting islet function. We conducted a randomized, double-blind, placebo-controlled trial. The study was performed in General Clinical Research Centers at two University Hospitals. Forty-one subjects with T2DM were treated with metformin or diet, having good glycemic control with glycosylated hemoglobin values of 6.2-7.5%. Subjects were treated with vildagliptin (50 mg twice daily) or placebo for 3 months, followed by a 2-wk washout. Major Outcome Measure: We measured insulin secretion in response to iv glucose and arginine before and after treatment and after drug washout. There were small and comparable reductions in glycosylated hemoglobin in both groups over 3 months. Vildagliptin increased fasting GLP-1 levels in subjects taking metformin, but not those managed with diet, and raised active GIP levels slightly. DPP-4 inhibitor treatment improved the acute insulin and C-peptide responses to glucose (50 and 100% respectively; P fasting conditions. This suggests that DPP-4 inhibition has metabolic benefits in addition to enhancing meal-induced GLP-1 and GIP activity.

Recombinant hemoglobin II from Lucina pectinata: a large-scale method for hemeprotein expression in E. coli.

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Ramos, Cacimar; Pietri, Ruth; Lorenzo, Wilmarie; Roman, Elddie; Granell, Laura B; Cadilla, Carmen L; López-Garriga, Juan

2010-02-01

Hemoglobin II from the clam L. pectinata is an O(2) reactive protein that remains oxygenated in the presence of other molecules. To determine the mechanism of ligand selection in this hemoglobin, rHbII was expressed in large quantities using an improved fermentation process. The highest protein yield was obtained by: transforming HbII into the BLi5 cells, inducing and supplementing the culture during the mid-log phase with 1 mM IPTG, 30 microg/mL hemin chloride and 1% glucose, and decreasing the temperature to 30 degrees C after induction. In addition, cell culture density was greatly enhanced by using glycerol, adding MgSO(4), supplementing the media with glucose after the glycerol was consumed and maintaining the dissolved oxygen at 35%. Under these conditions the maximum protein yield obtained was approximately 2,300 mg/L. The results indicate that rHbII is similar to the native protein. The protocol was validated with other hemoglobins, indicating that it can be extended to other hemeproteins.

Hemoglobin fructation promotes heme degradation through the generation of endogenous reactive oxygen species

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Goodarzi, M.; Moosavi-Movahedi, A. A.; Habibi-Rezaei, M.; Shourian, M.; Ghourchian, H.; Ahmad, F.; Farhadi, M.; Saboury, A. A.; Sheibani, N.

2014-09-01

Protein glycation is a cascade of nonenzymatic reactions between reducing sugars and amino groups of proteins. It is referred to as fructation when the reducing monosaccharide is fructose. Some potential mechanisms have been suggested for the generation of reactive oxygen species (ROS) by protein glycation reactions in the presence of glucose. In this state, glucose autoxidation, ketoamine, and oxidative advance glycation end products (AGEs) formation are considered as major sources of ROS and perhaps heme degradation during hemoglobin glycation. However, whether fructose mediated glycation produces ROS and heme degradation is unknown. Here we report that ROS (H2O2) production occurred during hemoglobin fructation in vitro using chemiluminescence methods. The enhanced heme exposure and degradation were determined using UV-Vis and fluorescence spectrophotometry. Following accumulation of ROS, heme degradation products were accumulated reaching a plateau along with the detected ROS. Thus, fructose may make a significant contribution to the production of ROS, glycation of proteins, and heme degradation during diabetes.

Hemoglobin C disease

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Clinical hemoglobin C ... Hemoglobin C is an abnormal type of hemoglobin, the protein in red blood cells that carries oxygen. It is ... Americans. You are more likely to have hemoglobin C disease if someone in your family has had ...

Imeglimin lowers glucose primarily by amplifying glucose-stimulated insulin secretion in high-fat-fed rodents

DEFF Research Database (Denmark)

Perry, Rachel J; Cardone, Rebecca L; Petersen, Max C

2016-01-01

Imeglimin is a promising new oral antihyperglycemic agent that has been studied in clinical trials as a possible monotherapy or add-on therapy to lower fasting plasma glucose and improve hemoglobin A1c (1-3, 9). Imeglimin was shown to improve both fasting and postprandial glycemia and to increase...

Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09.

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Chen, Yun-mei; Xu, Hai-yang; Wang, Yang; Zhang, Jian-fa; Wang, Shi-ming

2014-11-01

Salecan is a novel exopolysaccharide produced by the strain Agrobacterium sp. ZX09, and it is composed of only glucose monomers. The unique chemical composition and excellent physicochemical properties make Salecan a promising material for applications in coagulation, lubrication, protection against acute liver injury, and alleviating constipation. In this study, we cloned the Vitreoscilla hemoglobin gene into a broad-host-range plasmid pCM158. Without antibiotic selection, there was negligible loss of the plasmid in the host Agrobacterium sp. ZX09 after one passage of cultivation. The expression of Vitreoscilla hemoglobin was demonstrated by carbon monoxide (CO) difference spectrum. The engineered strain Agrobacterium sp. ZX09 increased Salecan yield by 30%. The other physiological changes included its elevated respiration rate and cellular invertase activity.

Engineering Mammalian Mucin-type O-Glycosylation in Plants

DEFF Research Database (Denmark)

Yang, Zhang; Drew, Damian P; Jørgensen, Bodil

2012-01-01

-glycans are attached to proteins, and which structures are formed, difficult. Because plants are devoid of GalNAc-type O-glycosylation, we have assessed requirements for establishing human GalNAc O-glycosylation de novo in plants with the aim of developing cell systems with custom-designed O-glycosylation capacity...... was glycosylated with up to three and five GalNAc residues when co-expressed with GalNAc-T2 and a combination of GalNAc-T2 and GalNAc-T4, respectively, as determined by mass spectrometry. O-Glycosylation was furthermore demonstrated on a tandem repeat of MUC16 and interferon a2b. In plants, prolines in certain...... classes of proteins are hydroxylated and further substituted with plant-specific O-glycosylation; unsubstituted hydroxyprolines were identified in our MUC1 construct. In summary, this study demonstrates that mammalian type O-glycosylation can be established in plants and that plants may serve as a host...

Trans-species Engineering of Glycosylated Therapeutic Proteins

DEFF Research Database (Denmark)

Yang, Zhang

important to address. Whenever glycosylation has been found to be an important PTM for function or bioactivity, human therapeutics have generally been produced in mammalian Chinese hamster ovary (CHO) cell line. Oglycosylation is one of the most complex regulated PTMs of proteins but also one of the least...... understood. Currently, mammalian cells are required for human O-glycosylation. Increasing efforts have been devoted to engineering non-mammalian cells for production of recombinant proteins with “human-like” glycosylation. Substantial success has been achieved with designed N-glycosylation in both lower......Recombinant expression of therapeutic proteins is one of the major tasks in modern biomedicine. One of the most important factors with respect to therapeutic use in human is posttranslational modifications (PTMs) of the recombinant proteins, of which protein glycosylation is by far the most...

Influence of insulin sensitivity and secretion on glycated albumin and hemoglobin A1c in pregnant women with gestational diabetes mellitus.

Science.gov (United States)

Pan, Jiemin; Zhang, Feng; Zhang, Lei; Bao, Yuqian; Tao, Minfang; Jia, Weiping

2013-06-01

To examine the differential effects of insulin sensitivity and secretion on hemoglobin A1c (HbA1c) and glycated albumin (GA) at 24-32weeks of pregnancy in women with gestational diabetes mellitus (GDM). A cross-sectional, sequential case series study was performed in pregnant women with an abnormal 50-g oral glucose-screening test. Hemoglobin A1c and GA measurements were taken during oral glucose tolerance test (OGTT). The homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-%β), insulin sensitivity index (ISOGTT), and modified insulinogenic index were calculated to assess insulin sensitivity and secretory function. A total of 713 pregnant women were enrolled. The GDM group had lower ISOGTT and insulinogenic index scores, and a higher HOMA-IR score. Hemoglobin A1c was positively correlated with HOMA-IR. Glycated albumin was negatively correlated with insulinogenic index and HOMA-%β. Multiple regression analysis revealed that HbA1c was independently associated with diastolic pressure, 0- and 120-minute glucose, and HOMA-IR; GA was independently associated with 0- and 120-minute glucose. Compared with HbA1c, GA is more closely correlated with fasting and postprandial glucose, regardless of insulin resistance and blood pressure, and might be a better monitoring index in women with GDM. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats

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Kumar Suresh

2012-08-01

Full Text Available Abstract Aim of the study This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham. Nees & Eberm (Tejpat oil (CTO in streptozotocin (STZ induced diabetes in rats along with evaluation of chemical constituents. Materials and methods The GC-MS (Gas chromatography–mass spectrometry analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%. CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results CTO (100 mg/kg and 200 mg/kg, cinnamaldehyde (20 mg/kg and glibenclamide (0.6 mg/kg in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA and increased reduced glutathione (GSH. Conclusion Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

OpenAIRE

Murphy, P A; Cebula, T A; Windle, B E

1981-01-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of a...

Identification of a general O-linked protein glycosylation system in Acinetobacter baumannii and its role in virulence and biofilm formation.

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Jeremy A Iwashkiw

Full Text Available Acinetobacter baumannii is an emerging cause of nosocomial infections. The isolation of strains resistant to multiple antibiotics is increasing at alarming rates. Although A. baumannii is considered as one of the more threatening "superbugs" for our healthcare system, little is known about the factors contributing to its pathogenesis. In this work we show that A. baumannii ATCC 17978 possesses an O-glycosylation system responsible for the glycosylation of multiple proteins. 2D-DIGE and mass spectrometry methods identified seven A. baumannii glycoproteins, of yet unknown function. The glycan structure was determined using a combination of MS and NMR techniques and consists of a branched pentasaccharide containing N-acetylgalactosamine, glucose, galactose, N-acetylglucosamine, and a derivative of glucuronic acid. A glycosylation deficient strain was generated by homologous recombination. This strain did not show any growth defects, but exhibited a severely diminished capacity to generate biofilms. Disruption of the glycosylation machinery also resulted in reduced virulence in two infection models, the amoebae Dictyostelium discoideum and the larvae of the insect Galleria mellonella, and reduced in vivo fitness in a mouse model of peritoneal sepsis. Despite A. baumannii genome plasticity, the O-glycosylation machinery appears to be present in all clinical isolates tested as well as in all of the genomes sequenced. This suggests the existence of a strong evolutionary pressure to retain this system. These results together indicate that O-glycosylation in A. baumannii is required for full virulence and therefore represents a novel target for the development of new antibiotics.

Identification of a General O-linked Protein Glycosylation System in Acinetobacter baumannii and Its Role in Virulence and Biofilm Formation

Science.gov (United States)

Iwashkiw, Jeremy A.; Seper, Andrea; Weber, Brent S.; Scott, Nichollas E.; Vinogradov, Evgeny; Stratilo, Chad; Reiz, Bela; Cordwell, Stuart J.; Whittal, Randy; Schild, Stefan; Feldman, Mario F.

2012-01-01

Acinetobacter baumannii is an emerging cause of nosocomial infections. The isolation of strains resistant to multiple antibiotics is increasing at alarming rates. Although A. baumannii is considered as one of the more threatening “superbugs” for our healthcare system, little is known about the factors contributing to its pathogenesis. In this work we show that A. baumannii ATCC 17978 possesses an O-glycosylation system responsible for the glycosylation of multiple proteins. 2D-DIGE and mass spectrometry methods identified seven A. baumannii glycoproteins, of yet unknown function. The glycan structure was determined using a combination of MS and NMR techniques and consists of a branched pentasaccharide containing N-acetylgalactosamine, glucose, galactose, N-acetylglucosamine, and a derivative of glucuronic acid. A glycosylation deficient strain was generated by homologous recombination. This strain did not show any growth defects, but exhibited a severely diminished capacity to generate biofilms. Disruption of the glycosylation machinery also resulted in reduced virulence in two infection models, the amoebae Dictyostelium discoideum and the larvae of the insect Galleria mellonella, and reduced in vivo fitness in a mouse model of peritoneal sepsis. Despite A. baumannii genome plasticity, the O-glycosylation machinery appears to be present in all clinical isolates tested as well as in all of the genomes sequenced. This suggests the existence of a strong evolutionary pressure to retain this system. These results together indicate that O-glycosylation in A. baumannii is required for full virulence and therefore represents a novel target for the development of new antibiotics. PMID:22685409

Porcine dentin sialoprotein glycosylation and glycosaminoglycan attachments.

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Yamakoshi, Yasuo; Nagano, Takatoshi; Hu, Jan Cc; Yamakoshi, Fumiko; Simmer, James P

2011-02-03

Dentin sialophosphoprotein (Dspp) is a multidomain, secreted protein that is critical for the formation of tooth dentin. Mutations in DSPP cause inherited dentin defects categorized as dentin dysplasia type II and dentinogenesis imperfecta type II and type III. Dentin sialoprotein (Dsp), the N-terminal domain of dentin sialophosphoprotein (Dspp), is a highly glycosylated proteoglycan, but little is known about the number, character, and attachment sites of its carbohydrate moieties. To identify its carbohydrate attachment sites we isolated Dsp from developing porcine molars and digested it with endoproteinase Glu-C or pronase, fractionated the digestion products, identified fractions containing glycosylated peptides using a phenol sulfuric acid assay, and characterized the glycopeptides by N-terminal sequencing, amino acid analyses, or LC/MSMS. To determine the average number of sialic acid attachments per N-glycosylation, we digested Dsp with glycopeptidase A, labeled the released N-glycosylations with 2-aminobenzoic acid, and quantified the moles of released glycosylations by comparison to labeled standards of known concentration. Sialic acid was released by sialidase digestion and quantified by measuring β-NADH reduction of pyruvic acid, which was generated stoichiometrically from sialic acid by aldolase. To determine its forms, sialic acid released by sialidase digestion was labeled with 1,2-diamino-4,5-methyleneoxybenzene (DMB) and compared to a DMB-labeled sialic acid reference panel by RP-HPLC. To determine the composition of Dsp glycosaminoglycan (GAG) attachments, we digested Dsp with chondroitinase ABC and compared the chromotagraphic profiles of the released disaccharides to commercial standards. N-glycosylations were identified at Asn37, Asn77, Asn136, Asn155, Asn161, and Asn176. Dsp averages one sialic acid per N-glycosylation, which is always in the form of N-acetylneuraminic acid. O-glycosylations were tentatively assigned at Thr200, Thr216 and Thr

Porcine dentin sialoprotein glycosylation and glycosaminoglycan attachments

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Yamakoshi Fumiko

2011-02-01

Full Text Available Abstract Background Dentin sialophosphoprotein (Dspp is a multidomain, secreted protein that is critical for the formation of tooth dentin. Mutations in DSPP cause inherited dentin defects categorized as dentin dysplasia type II and dentinogenesis imperfecta type II and type III. Dentin sialoprotein (Dsp, the N-terminal domain of dentin sialophosphoprotein (Dspp, is a highly glycosylated proteoglycan, but little is known about the number, character, and attachment sites of its carbohydrate moieties. Results To identify its carbohydrate attachment sites we isolated Dsp from developing porcine molars and digested it with endoproteinase Glu-C or pronase, fractionated the digestion products, identified fractions containing glycosylated peptides using a phenol sulfuric acid assay, and characterized the glycopeptides by N-terminal sequencing, amino acid analyses, or LC/MSMS. To determine the average number of sialic acid attachments per N-glycosylation, we digested Dsp with glycopeptidase A, labeled the released N-glycosylations with 2-aminobenzoic acid, and quantified the moles of released glycosylations by comparison to labeled standards of known concentration. Sialic acid was released by sialidase digestion and quantified by measuring β-NADH reduction of pyruvic acid, which was generated stoichiometrically from sialic acid by aldolase. To determine its forms, sialic acid released by sialidase digestion was labeled with 1,2-diamino-4,5-methyleneoxybenzene (DMB and compared to a DMB-labeled sialic acid reference panel by RP-HPLC. To determine the composition of Dsp glycosaminoglycan (GAG attachments, we digested Dsp with chondroitinase ABC and compared the chromotagraphic profiles of the released disaccharides to commercial standards. N-glycosylations were identified at Asn37, Asn77, Asn136, Asn155, Asn161, and Asn176. Dsp averages one sialic acid per N-glycosylation, which is always in the form of N-acetylneuraminic acid. O-glycosylations were

[The influence of nettle and burdock extracts in combination with different diets on dyslipidemia in diabetes mellitus model].

Science.gov (United States)

Vengerovsky, A I; Yakimova, T V; Nasanova, O N

2015-01-01

The influence of low-fat diet, nettle (Urtica dioica) leafs and burdock (Arctium lappa) roots extracts on lipid metabolism and glycosylation reactions has been investigated in experimental diabetes mellitus. These extracts were applied in diets with both high and low fat content. The experiments were performed on 90 noninbred male albino rats (200–220 g) that were divided into 9 experimental groups. Diabetes mellitus was modeled with twice-repeated intraperitoneal streptozotocin (30 mg/kg) injections. The animals received food with increased fat content (proteins – 8%, fats – 30%, carbohydrates – 62% of total daily caloric content) during 4 weeks before streptozotocine injections and 8 weeks after its discontinuation. Simultaneously the rats were daily administered nettle leafs (100 mg/kg), burdock roots (25 mg/kg) extracts or metformin (100 mg/kg) into the stomach during 10 days. During the period of agents introduction half the animals continued to receive food with high fat content, the other half received low fat diet (proteins – 20%, fats – 8%, carbohydrates – 72% of the total daily caloric content). The forth (control) group received low fat food only without extracts or metformin administration. The levels of blood glucose, glycosylated hemoglobin, malonic dialdehyde, lipid and lipoprotein fractions content were measured. It has been shown that after streptozotocine injections and 30% fat diet consumption the blood glucose level increased by 5.3 fold compared to that of the intact animals, the content of atherogenic lipid fractions increased by 2–8.3 fold and the protein glycosylation reactions were intensified by 1.9–2.5 fold. In animals fed with 8% fat diet the blood glucose and malonic dialdehyde content decreased by 1.8–2.3 fold. In this experiment the levels of triglycerides, total cholesterol, cholesterol of nonhigh-density lipoproteins, low-density and very low-density lipoproteins, as well as the cholesterol and protein content of

Comparison of Hemoglobin A1c assay performance on two different commercial systems

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Jozo Ćorić

2015-04-01

Full Text Available Introduction: Glycated hemoglobin (HbA1c is formed by non-enzymatic binding of glucose to the free amino group of the N-terminal end of the ß-chain of hemoglobin A. HbA1c is representative of the mean blood glucose level over three months. The aim of the study was to evaluate the Hemoglobin A1c immunoturbidimetric assay performance on two different commercial systems.Methods: We evaluated the precision and trueness for determination of HbA1c in whole blood. Concentrations of total hemoglobin and HbA1c were evaluated on Dimension Xpand (Siemens and Cobas 501 (Roche analyzers. HbA1c was measured in a latex agglutination inhibition test. Commercial controls Liquichek Diabetes Control Level 1 and Liquichek Diabetes Control Level 2 (Bio Rad at two levels were used for quality control. Analytical validation of HbA1c included: within-run imprecision, between-day imprecision, inaccuracy and comparison determination on the human samples on 2 systems: Dimension Xpand and Cobas 501 analyzers. Results: Within-run imprecision on the commercially controls for Level 1 is 4.5% and Level 2 is 3.2% between-day imprecision on commercially controls is 6.1% Level 1 and 5.1% Level 2 for respectively inac- curacy on commercially controls for Level 1 is 1.8% and Level 2 is 4.8%. Method comparison on human samples shows the correlation coefficient of 0.99.Conclusion: The presented results of the analytical evaluation methods for the determination of HbA1c showed an acceptable accuracy and precision.

Cell culture media supplementation of infrequently used sugars for the targeted shifting of protein glycosylation profiles.

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Hossler, Patrick; Racicot, Christopher; Chumsae, Christopher; McDermott, Sean; Cochran, Keith

2017-03-01

Mammalian cells in culture rely on sources of carbohydrates to supply the energy requirements for proliferation. In addition, carbohydrates provide a large source of the carbon supply for supporting various other metabolic activities, including the intermediates involved in the protein glycosylation pathway. Glucose and galactose, in particular, are commonly used sugars in culture media for these purposes. However, there exists a very large repertoire of other sugars in nature, and many that have been chemically synthesized. These sugars are particularly interesting because they can be utilized by cells in culture in distinct ways. In the present work it has been found that many infrequently used sugars, and the corresponding cellular response towards them as substrates, led to differences in the protein N-glycosylation profile of a recombinant glycoprotein. The selective media supplementation of raffinose, trehalose, turanose, palatinose, melezitose, psicose, lactose, lactulose, and mannose were found to be capable of redirecting N-glycan oligosaccharide profiles. Despite this shifting of protein glycosylation, there were no other adverse changes in culture performance, including both cell growth and cellular productivity over a wide range of supplemented sugar concentrations. The approach presented highlights a potential means towards both the targeted shifting of protein glycosylation profiles and ensuring recombinant protein comparability, which up to this point in time has remained under-appreciated for these under-utilized compounds. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:511-522, 2017. © 2017 American Institute of Chemical Engineers.

Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

DEFF Research Database (Denmark)

Gils, Ann; Pedersen, Katrine Egelund; Skottrup, Peter

2003-01-01

The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosyla......The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous...... with the glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended...

Glycosylation: a hallmark of cancer?

Science.gov (United States)

Vajaria, Bhairavi N; Patel, Prabhudas S

2017-04-01

The hallmarks of cancer are characterized by functional capabilities that allow cancer cells to survive, proliferate and disseminate during the multistep tumorigenesis. Cancer being a cellular disease, changes in cellular glycoproteins play an important role in malignant transformation and cancer progression. The present review summarizes various studies that depicted correlation of glycosylation with tumor initiation, progression and metastasis, which are helpful in early diagnosis, disease monitoring and prognosis. The results are further strengthened by our reports, which depicted alterations in sialylation and fucosylation in different cancers. Alterations in glycosyltransferases are also involved in formation of various tumor antigens (e.g. Sialyl Lewis x) which serves as ligand for the cell adhesion molecule, selectin which is involved in adhesion of cancer cells to vascular endothelium and thus contributes to hematogenous metastasis. Increased glycosylation accompanied by alterations in glycosyltranferases, glycosidases, glycans and mucins (MUC)s are also involved in loss of E-cadherin, a key molecule implicated in metastatic dissemination of cells. The present review also summarizes the correlation of glycosylation with all the hallmarks of cancer. The enormous progress in the design of novel inhibitors of pathway intermediates of sialylation and fucosylation can prove wonders in combating the dreadful disease. The results provide the evidence that altered glycosylation is linked to tumor initiation, progression and metastasis. Hence, it can be considered as a new hallmark of cancer development and strategies to develop novel glycosylation targeted molecules should be strengthened.

Quality of life in Asians with type-2 diabetes mellitus: development and validation of ethnic and language specific questionnaires, a cross-sectional study in Malaysia.

OpenAIRE

Goh, Giap Kah

2017-01-01

Diabetes mellitus (DM) is a complex and chronic disease with multiple complications leading to increased mortality and poor quality of life. Current studies have shown that lowering glycosylated hemoglobin (HbA1c) confers protection against microvascular complications. However, evidence showed that with more intensive glucose control to achieve HbA1c of less than 6.5%, there is a significant increased risk of mortality and cardiovascular events. The current recommendation worldwide i...

Dietary Inflammatory Index and Cardiometabolic Risk Parameters in Overweight and Sedentary Subjects

OpenAIRE

Camargo-Ramos, Claudia Marcela; Correa-Bautista, Jorge Enrique; Correa-Rodríguez, María; Ramírez-Vélez, Robinson

2017-01-01

Nutrition has been established as a relevant factor in the development of cardiovascular disease (CVD). We aimed to investigate the relationship between the dietary inflammatory index (DII) and cardiometabolic risk parameters in a cohort of 90 overweight and sedentary adults from Bogotá, Colombia. A 24-h dietary record was used to calculate the DII. Body composition variables, flow-mediated dilation (FMD), pulse wave velocity (PWV), lipid profile, glucose, glycosylated hemoglobin (Hb1Ac), and...

The role of O-linked GlcNAc modification on the glucose response of ChREBP

Energy Technology Data Exchange (ETDEWEB)

Sakiyama, Haruhiko [Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Fujiwara, Noriko, E-mail: noriko-f@hyo-med.ac.jp [Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Noguchi, Takahiro; Eguchi, Hironobu; Yoshihara, Daisaku [Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Uyeda, Kosaku [Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, TX 75390-9038 (United States); Suzuki, Keiichiro [Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan)

2010-11-26

Research highlights: {yields} The O-linked GlcNAc modification is crucial for the glucose response. {yields} Mlx is required for nuclear localization and transcription activity of ChREBP. {yields} The presence of Mlx stabilizes ChREBP protein. -- Abstract: The carbohydrate response element-binding protein (ChREBP) functions as a transcription factor in mediating the glucose-activated gene expression of multiple liver enzymes, which are responsible for converting excess carbohydrate to storage fat. ChREBP is translocated into the nucleus in response to high glucose levels, and then up-regulates transcriptional activity. Although this glucose activation of ChREBP is generally observed only in liver cells, overexpression of wild type max-like protein X (Mlx), but not an inactive mutant Mlx, resulted in the exhibition of the ChREBP functions also in a human kidney cell line. Because high glucose conditions induce the glycosylation of cellular proteins, the effect of O-linked GlcNAc modification on ChREBP functions was examined. Treatment with an O-GlcNAcase inhibitor (PUGNAc), which increases the O-linked GlcNAc modification of cellular proteins, caused an increase in the glucose response of ChREBP. In contrast, treatment with a glutamine fructose amidotransferase inhibitor (DON), which decreases O-GlcNAcylation by inhibiting the hexosamine biosynthetic pathway, completely blocked the glucose response of ChREBP. These results suggest that the O-linked glycosylation of ChREBP itself or other proteins that regulate ChREBP is essential for the production of functional ChREBP.

Synergizing metabolic flux analysis and nucleotide sugar metabolism to understand the control of glycosylation of recombinant protein in CHO cells

LENUS (Irish Health Repository)

Burleigh, Susan C

2011-10-18

Abstract Background The glycosylation of recombinant proteins can be altered by a range of parameters including cellular metabolism, metabolic flux and the efficiency of the glycosylation process. We present an experimental set-up that allows determination of these key processes associated with the control of N-linked glycosylation of recombinant proteins. Results Chinese hamster ovary cells (CHO) were cultivated in shake flasks at 0 mM glutamine and displayed a reduced growth rate, glucose metabolism and a slower decrease in pH, when compared to other glutamine-supplemented cultures. The N-linked glycosylation of recombinant human chorionic gonadotrophin (HCG) was also altered under these conditions; the sialylation, fucosylation and antennarity decreased, while the proportion of neutral structures increased. A continuous culture set-up was subsequently used to understand the control of HCG glycosylation in the presence of varied glutamine concentrations; when glycolytic flux was reduced in the absence of glutamine, the glycosylation changes that were observed in shake flask culture were similarly detected. The intracellular content of UDP-GlcNAc was also reduced, which correlated with a decrease in sialylation and antennarity of the N-linked glycans attached to HCG. Conclusions The use of metabolic flux analysis illustrated a case of steady state multiplicity, where use of the same operating conditions at each steady state resulted in altered flux through glycolysis and the TCA cycle. This study clearly demonstrated that the control of glycoprotein microheterogeneity may be examined by use of a continuous culture system, metabolic flux analysis and assay of intracellular nucleotides. This system advances our knowledge of the relationship between metabolic flux and the glycosylation of biotherapeutics in CHO cells and will be of benefit to the bioprocessing industry.

Competition between folding and glycosylation in the endoplasmic reticulum

DEFF Research Database (Denmark)

Holst, B; Bruun, A W; Kielland-Brandt, Morten

1996-01-01

Using carboxypeptidase Y in Saccharomyces cerevisiae as a model system, the in vivo relationship between protein folding and N-glycosylation was studied. Seven new sites for N-glycosylation were introduced at positions buried in the folded protein structure. The level of glycosylation of such new...... acceptor sites. In some cases, all the newly synthesized mutant protein was modified at the novel site while in others no modification took place. In the most interesting category of mutants, the level of glycosylation was dependent on the conditions for folding. This shows that folding and glycosylation...

HbA1c levels in individuals heterozygous for hemoglobin variants.

Science.gov (United States)

Tavares, Ricardo Silva; Souza, Fábio Oliveira de; Francescantonio, Isabel Cristina Carvalho Medeiros; Soares, Weslley Carvalho; Mesquita, Mauro Meira

2017-04-01

To evaluate the levels of glycated hemoglobin (HbA1c) in patients heterozygous for hemoglobin variants and compare the results of this test with those of a control group. This was an experimental study based on the comparison of HbA1c tests in two different populations, with a test group represented by individuals heterozygous for hemoglobin variants (AS and AC) and a control group consisting of people with electrophoretic profile AA. The two populations were required to meet the following inclusion criteria: Normal levels of fasting glucose, hemoglobin, urea and triglycerides, bilirubin > 20 mg/dL and non-use of acetylsalicylic acid. 50 heterozygous subjects and 50 controls were evaluated between August 2013 and May 2014. The comparison of HbA1c levels between heterozygous individuals and control subjects was performed based on standard deviation, mean and G-Test. The study assessed a test group and a control group, both with 39 adults and 11 children. The mean among heterozygous adults for HbA1c was 5.0%, while the control group showed a rate of 5.74%. Heterozygous children presented mean HbA1c at 5.11%, while the controls were at 5.78%. G-Test yielded p=0.93 for children and p=0.89 for adults. Our study evaluated HbA1c using ion exchange chromatography resins, and the patients heterozygous for hemoglobin variants showed no significant difference from the control group.

Aerobic bacterial microbiota of the conjunctiva in diabetic patients with normal and altered glycated hemoglobin levels in two regions in Brazil

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Natalia Pimentel Moreno

2014-12-01

Full Text Available Purpose: To study the aerobic bacterial microbiota of the conjunctiva in diabetic patients with regard to the management of diabetes, assessed using glycated hemoglobin levels. Methods: A cross-sectional study was conducted using conjunctival smears of diabetic patients from both sexes and with different ages, residing in two different Brazilian cities (Sorocaba and Rio Branco. A control group of non-diabetic patients was also included. The diabetic patients were considered to have controlled diabetes when their glycated hemoglobin level was ≤7% and blood glucose level was ≤126 mg/dL. Patients with non-controlled diabetes were those with glycated hemoglobin levels >7% and blood glucose levels >126 mg/dL. The samples obtained were inoculated in Brain-Heart Infusion broth and in culture media for aerobic bacteria (blood and chocolate agars; bacterial growth was evaluated in a microbiology laboratory. Results: A total of 120 eyes of 120 patients were included in the present study. The percentage of cultures in which bacterial growth was observed was greater in diabetic patients, although the difference was not statistically significant (p=0.103. There was a greater trend toward bacterial growth in the conjunctiva of diabetic patients with altered fasting blood glucose. There was no difference in the frequency of bacterial growth on the conjunctiva between diabetic patients with normal or altered glycated hemoglobin levels. In Sorocaba, conjunctival bacterial growth was similar to that observed in Rio Branco. The microorganism most frequently detected in the present study was Staphylococcus epidermidis, followed by Staphylococcus aureus, Proteus mirabilis, and Escherichia coli. Conclusion: There was no difference between diabetic patients with normal or altered glycated hemoglobin levels. The microorganisms found were similar to those found in studies investigating the conjunctival bacterial flora of diabetic and non-diabetic patients.

Newly detected abnormal glucose regulation and long-term prognosis after acute myocardial infarction

DEFF Research Database (Denmark)

Pararajasingam, Gokulan; Høfsten, Dan Eik; Løgstrup, Brian Bridal

2016-01-01

BACKGROUND: An oral glucose tolerance test (OGTT) and/or glycosylated haemoglobin A1c (HbA1c) in patients with acute myocardial infarction (AMI) identify patients with increased mortality risk, but no comparison of the long-term prognostic values has yet been investigated. METHODS: This study...... to patients categorized as normal/impaired fasting glycaemia/impaired glucose tolerance by OGTT and HbA1c values. CONCLUSION: An OGTT is recommended in AMI patients without known DM...

Prevalence of Type 2 Diabetes and Impaired Glucose Regulation with Associated Cardiometabolic Risk Factors and Depression in an Urbanizing Rural Community in Bangladesh: A Population-Based Cross-Sectional Study

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Bishwajit Bhowmik

2012-12-01

Full Text Available BackgroundTo determine the prevalence of type 2 diabetes (T2DM and impaired glucose regulation (impaired fasting glucose [IFG] and impaired glucose tolerance [IGT] in an urbanizing rural population of Bangladesh and associated cardiometabolic risk indicators and depression.MethodsA total of 2,293 subjects aged ≥20 years in an urbanizing rural Bangladeshi community were investigated. Socio-demographic and anthropometric details, blood pressure, fasting plasma glucose (FPG, 2 hours after 75 g plasma glucose (2hPG, glycosylated hemoglobin, fasting serum insulin and lipid profiles were studied. Presence of depressive symptoms using Montogomery-Asberg Depression Rating Scale was also assessed.ResultsThe prevalence of IFG, IGT, IFG+IGT, and T2DM were 3.4%, 4.0%, 1.2%, and 7.9%, respectively. The prevalence of T2DM and impaired glucose regulation differed between males and females, but, both increased with age in both sexes. FPG and 2hPG had positive correlation. Employing logistic regression, it was found that increased age, waist to hip ratio, systolic blood pressure, total cholesterol, triglycerides, and depression were independent risk indicators for diabetes. Both insulin resistance and β-cell deficiency were significantly related for causation of diabetes. Among the study population, 26.2% had general obesity, 39.8% central obesity, 15.5% hypertension, 28.7% dyslipidemia, 17.6% family history of diabetes, and 15.3% had depression. Physical inactivity and smoking habits were significantly higher in male.ConclusionRising prevalence of diabetes and impaired glucose regulation in this urbanizing rural population exist as a significant but hidden public health problem. Depression and other cardiometabolic risk indicators including obesity, hypertension, and dyslipdemia were also prevalent in this population.

Spin Label Studies of the Hemoglobin-Membrane Interaction During Sickle Hemoglobin Polymerization

International Nuclear Information System (INIS)

Falcon Dieguez, Jose E.; Rodi, Pablo; Lores Guevara, Manuel A.; Gennaro, Ana Maria

2009-12-01

An enhanced hemoglobin-membrane association has been previously documented in Sickle Cell Anemia. However, it is not known how this interaction is modified during the hemoglobin S polymerization process. In this work, we use a model of reconstituted erythrocytes from ghost membranes whose cytoskeleton proteins had been previously labeled with the 4-maleimido Tempo spin label, and that were subsequently resealed with hemoglobin S or A solutions. Using EPR spectroscopy, we studied the time dependence of the spectral W/S parameter, indicative of the conformational state of cytoskeleton proteins (mainly spectrin) under spontaneous deoxygenation, with the aim of detecting the eventual effects due to hemoglobin S polymerization. The differences observed in the temporal behaviour of W/S in erythrocytes reconstituted with both hemoglobins were considered as experimental evidence of an increment in hemoglobin S-membrane interaction, as a result of the polymerization process of hemoglobin S under spontaneous deoxygenation. (author)

Snack patterns are associated with biomarkers of glucose metabolism in US men.

Science.gov (United States)

Shin, Dayeon; Song, SuJin; Krumhar, Kim; Song, Won O

2015-01-01

Few studies have made distinctions between dietary intake from meals and snacks in relating them to biomarkers. We aimed to examine if snack patterns are associated with biomarkers of glucose metabolism, specifically hemoglobin A1c and HOMA-IR in US adults. Using 24-h dietary recall data from National Health and Nutrition Examination Survey (NHANES) in 2007-2008, we derived snack patterns using factor analyses. Multivariate logistic regressions were performed to estimate adjusted odds ratios (AOR) for biomarkers of glucose metabolism by quintiles of snack pattern scores. Men in the highest quintile of dairy and sugary snack pattern had higher risk of having hemoglobin A1c ≥ 6.5% (AOR: 2.06; 95% CI: 1.20-3.51) and HOMA-IR > 3.0 (AOR: 1.73; 95% CI: 1.01-2.95) than did those in the lowest quintile. No significant association was found in women between snack patterns and biomarkers of glucose metabolism. Dairy and sugary snack patterns of US men had the greatest association with poor control of glucose metabolism.

Fasting blood glucose and haemoglobin concentrations of healthy ...

African Journals Online (AJOL)

Menstruation is associated with loss of blood monthly in women of reproductive age. In some women this physiological phenomenon is also associated with some complaints such as menstrual pain, vomiting, and tiredness. We investigated the fasting blood glucose concentration and hemoglobin concentration before and ...

Hemoglobin (image)

Science.gov (United States)

Hemoglobin is the most important component of red blood cells. It is composed of a protein called ... exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in the normal balance ...

N-glycosylation in sugarcane

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Maia Ivan G.

2001-01-01

Full Text Available The N-linked glycosylation of secretory and membrane proteins is the most complex posttranslational modification known to occur in eukaryotic cells. It has been shown to play critical roles in modulating protein function. Although this important biological process has been extensively studied in mammals, much less is known about this biosynthetic pathway in plants. The enzymes involved in plant N-glycan biosynthesis and processing are still not well defined and the mechanism of their genetic regulation is almost completely unknown. In this paper we describe our first attempt to understand the N-linked glycosylation mechanism in a plant species by using the data generated by the Sugarcane Expressed Sequence Tag (SUCEST project. The SUCEST database was mined for sugarcane gene products potentially involved in the N-glycosylation pathway. This approach has led to the identification and functional assignment of 90 expressed sequence tag (EST clusters sharing significant sequence similarity with the enzymes involved in N-glycan biosynthesis and processing. The ESTs identified were also analyzed to establish their relative abundance.

Distinct associations of HbA(1c) and the urinary excretion of pentosidine, an advanced glycosylation end-product, with markers of endothelial function in insulin-dependent diabetes mellitus

NARCIS (Netherlands)

Smulders, R.A.; Stehouwer, C.D.A.; Schalkwijk, C.G.; Donker, A.J.M.; Hinsbergh, V.W.M. van; TeKoppele, J.M.

1998-01-01

Dysfunction of the vascular endothelium is considered an early step in the development of diabetic angiopathy. Hyperglycaemia results in endothelial dysfunction, both through direct effects of glucose and through formation of advanced glycosylation end-products (AGEs). We hypothesized that the

Communication competence, self-care behaviors and glucose control in patients with type 2 diabetes.

Science.gov (United States)

Parchman, Michael L; Flannagan, Dorothy; Ferrer, Robert L; Matamoras, Mike

2009-10-01

To examine the relationship between physician communication competence and A1c control among Hispanics and non-Hispanics seen in primary care practices. Observational. Direct observation and audio-recording of patient-physician encounters by 155 Hispanic and non-Hispanic white patients seen by 40 physicians in 20 different primary care clinics. Audio-recordings were transcribed and coded to derive an overall communication competence score for the physician. An exit survey was administered to each patient to assess self-care activities and their medical record was abstracted for the most recent glycosylated hemoglobin (A1c) level. Higher levels of communication competence were associated with lower levels of A1c for Hispanics, but not non-Hispanic white patients. Although communication competence was associated with better self-reported diet behaviors, diet was not associated with A1c control. Across all patients, higher levels of communication competence were associated with improved A1c control after controlling for age, ethnicity and diet adherence. Physician's communication competence may be more important for promoting clinical success in disadvantaged patients. Acquisition of communication competence skills may be an important component in interventions to eliminate Hispanic disparities in glucose control. Published by Elsevier Ireland Ltd.

Titania nanotubes decorated with gold nanoparticles for electrochemiluminescent biosensing of glycosylated hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Zhao, Qun [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China); College of Chemistry and Chemical Engineering, Nantong University, Nantong, 226019 (China); Tang, Shan [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China); Fang, Chen [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China); Second Affiliated Hospital, Soochow University, Suzhou, 215004 (China); Tu, Yi-Feng, E-mail: tuyf@suda.edu.cn [Institute of Analytical Chemistry, Dushu Lake Campus, Soochow University, Industrial Park, Suzhou, 215123 (China)

2016-09-14

A glycated hemoglobin (HbA1c) biosensor with high performance has been constructed in this work. Here the fructosyl amino acid oxidase was immobilized onto a pre-functionalized indium tin oxide glass with titania nanotubes decorated with gold nanoparticles. The property of nanocomposite was characterized by transmission electromicroscopy, scanning electron microscopy, electrochemistry and spectroscopy. Under the optimum conditions, fructosyl valine was detected by this biosensor. It exhibited a linear detection range from 4.0 × 10{sup −9} M to 7.2 × 10{sup −7} M, and a limit of detection for 3.8 × 10{sup −9} M at the signal-to-noise ratio of 3. Thus the HbA1c level in whole blood samples of healthy individuals or diabetic patients were evaluated with designed biosensor after pre-treatment of hydrolysis. The results of our detection were closely consistent with that of the standard method. At the same time, our biosensor has some advantages including high sensitivity, disposable usage and low cost, which implies its great promising application in point-of-care testing of HbA1c. - Highlights: • The enhanced electrochemiluminescence of luminol by AuNPs/TiNTs. • An ECL biosensor for HbA1c assay with ultra-high sensitivity. • A promising disposable device for diabetic diagnosis and treatment even for POCT. • The excellent regression of detected results with gold-standard method.

Titania nanotubes decorated with gold nanoparticles for electrochemiluminescent biosensing of glycosylated hemoglobin

International Nuclear Information System (INIS)

Zhao, Qun; Tang, Shan; Fang, Chen; Tu, Yi-Feng

2016-01-01

A glycated hemoglobin (HbA1c) biosensor with high performance has been constructed in this work. Here the fructosyl amino acid oxidase was immobilized onto a pre-functionalized indium tin oxide glass with titania nanotubes decorated with gold nanoparticles. The property of nanocomposite was characterized by transmission electromicroscopy, scanning electron microscopy, electrochemistry and spectroscopy. Under the optimum conditions, fructosyl valine was detected by this biosensor. It exhibited a linear detection range from 4.0 × 10"−"9 M to 7.2 × 10"−"7 M, and a limit of detection for 3.8 × 10"−"9 M at the signal-to-noise ratio of 3. Thus the HbA1c level in whole blood samples of healthy individuals or diabetic patients were evaluated with designed biosensor after pre-treatment of hydrolysis. The results of our detection were closely consistent with that of the standard method. At the same time, our biosensor has some advantages including high sensitivity, disposable usage and low cost, which implies its great promising application in point-of-care testing of HbA1c. - Highlights: • The enhanced electrochemiluminescence of luminol by AuNPs/TiNTs. • An ECL biosensor for HbA1c assay with ultra-high sensitivity. • A promising disposable device for diabetic diagnosis and treatment even for POCT. • The excellent regression of detected results with gold-standard method.

Insulin detemir for the treatment of obese patients with type 2 diabetes

OpenAIRE

Hollander, Priscilla A

2012-01-01

Priscilla A Hollander1,21Baylor Endocrine Center, 2Baylor Medical Center, Dallas, Texas, USAAbstract: The risk for developing type 2 diabetes (T2DM) is greater among obese individuals. Following onset of the disease, patients with T2DM become more likely to be afflicted with diabetic micro- and macrovascular complications. Decreasing body weight has been shown to lower glycosylated hemoglobin and improve other metabolic parameters in patients with T2DM. Medications used to lower blood glucose...

Mediation of glycosylated and partially-deglycosylated glucose oxidase of Aspergillus niger by a ferrocene-derivatised detergent.

Science.gov (United States)

Fraser, D M; Zakeeruddin, S M; Grätzel, M

1992-01-30

A ferrocene-derivatised detergent, (11-ferrocenylundecyl) trimethylammonium bromide (FTMAB), when oxidised to the corresponding ferricinium ion, was found by electrochemical studies to be an effective electron acceptor for reduced glucose oxidase of Aspergillus niger (EC 1.13.4) and thus acts as a electron-transfer mediator between glucose oxidase and a working electrode held at a potential sufficiently positive to reoxidise reduced FTMAB. An increase in mediating activity was produced when FTMAB was present in concentrations above its critical micelle concentration. An 'enzyme electrode' was formed by adsorption of glucose oxidase and FTMAB surfactant on a graphite rod. The electrode functioned as an amperometric biosensor for glucose in phosphate-buffered saline solution. A mixed micelle of glucose oxidase and FTMAB, probably adsorbed on the electrode surface, appears to be advantageous for the amperometric determination of glucose. Additionally, glucose oxidase was treated with alpha-mannosidase. When this partially-deglycosylated glucose oxidase was incorporated in an enzyme electrode, a 100-fold increase in the second-order rate constant (k) for electron transfer between the enzyme and FTMAB was observed, together with increased current densities, with respect to the equivalent values for FTMAB and commercial glucose oxidase. The use of deglycosylated enzymes in biosensors is suggested.

Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test

Directory of Open Access Journals (Sweden)

Rohit Babbar

2018-03-01

Full Text Available IntroductionImpaired glucose tolerance (IGT is diagnosed by a standardized oral glucose tolerance test (OGTT. However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.MethodsGiven a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA, proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1 year.ResultsThe most accurate prediction of IGT was reached with the recursive partitioning method (accuracy = 0.78. For all classifiers, mean accuracy was 0.73 ± 0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.ConclusionMachine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a

Nutritional Therapies in Congenital Disorders of Glycosylation (CDG

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Peter Witters

2017-11-01

Full Text Available Congenital disorders of glycosylation (CDG are a group of more than 130 inborn errors of metabolism affecting N-linked, O-linked protein and lipid-linked glycosylation. The phenotype in CDG patients includes frequent liver involvement, especially the disorders belonging to the N-linked protein glycosylation group. There are only a few treatable CDG. Mannose-Phosphate Isomerase (MPI-CDG was the first treatable CDG by high dose mannose supplements. Recently, with the successful use of d-galactose in Phosphoglucomutase 1 (PGM1-CDG, other CDG types have been trialed on galactose and with an increasing number of potential nutritional therapies. Current mini review focuses on therapies in glycosylation disorders affecting liver function and dietary intervention in general in N-linked glycosylation disorders. We also emphasize now the importance of early screening for CDG in patients with mild hepatopathy but also in cholestasis.

Hemoglobin

Science.gov (United States)

1993-03-08

affinity, which is less at low levels of hemoglobin saturation, increases markedly as fractional saturation increases. Thus, high affinity for 02 at... diphosphoglycerate (2,3-DPG), and carbon dioxide (Co 2). Since they are linked to 02 binding, they are called oxygen-linked effectors. The oxygen...hemoglobin molecule because of the negative charge of the ions. 2,3- Diphosphoglycerate is a molecule formed during the breakdown of sugar in normal human

Effect of yogic exercise on superoxide dismutase levels in diabetics

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Mahapure Hemant

2008-01-01

Full Text Available Context: Reactive oxygen species are known to aggravate disease progression. To counteract their harmful effects, the body produces various antioxidant enzymes, viz , superoxide dismutase, glutathione reductase etc. Literature reviews revealed that exercises help to enhance antioxidant enzyme systems; hence, yogic exercises may be useful to combat various diseases. Aims: This study aims to record the efficacy of yoga on superoxide dismutase, glycosylated hemoglobin (Hb and fasting blood glucose levels in diabetics. Settings and Design: Forty diabetics aged 40-55 years were assigned to experimental (30 and control (10 groups. The experimental subjects underwent a Yoga program comprising of various Asanas (isometric type exercises and Pranayamas (breathing exercises along with regular anti-diabetic therapy whereas the control group received anti-diabetic therapy only. Methods and Material: Heparinized blood samples were used to determine erythrocyte superoxide dismutase (SOD activity and glycosylated Hb levels and fasting blood specimens collected in fluoride Vacutainers were used for assessing blood glucose. Statistical analysis used: Data were analyzed by using 2 x 2 x 3 Factorial ANOVA followed by Scheffe′s posthoc test. Results: The results revealed that Yogic exercise enhanced the levels of Superoxide dismutase and reduced glycosylated Hb and glucose levels in the experimental group as compared to the control group. Conclusion: The findings conclude that Yogic exercises have enhanced the antioxidant defence mechanism in diabetics by reducing oxidative stress.

A glucose-centric perspective of hyperglycemia.

Science.gov (United States)

Ramasarma, T; Rafi, M

2016-02-01

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (> 200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and

Accuracy of hemoglobin A1c imputation using fasting plasma glucose in diabetes research using electronic health records data

Directory of Open Access Journals (Sweden)

Stanley Xu

2014-05-01

Full Text Available In studies that use electronic health record data, imputation of important data elements such as Glycated hemoglobin (A1c has become common. However, few studies have systematically examined the validity of various imputation strategies for missing A1c values. We derived a complete dataset using an incident diabetes population that has no missing values in A1c, fasting and random plasma glucose (FPG and RPG, age, and gender. We then created missing A1c values under two assumptions: missing completely at random (MCAR and missing at random (MAR. We then imputed A1c values, compared the imputed values to the true A1c values, and used these data to assess the impact of A1c on initiation of antihyperglycemic therapy. Under MCAR, imputation of A1c based on FPG 1 estimated a continuous A1c within ± 1.88% of the true A1c 68.3% of the time; 2 estimated a categorical A1c within ± one category from the true A1c about 50% of the time. Including RPG in imputation slightly improved the precision but did not improve the accuracy. Under MAR, including gender and age in addition to FPG improved the accuracy of imputed continuous A1c but not categorical A1c. Moreover, imputation of up to 33% of missing A1c values did not change the accuracy and precision and did not alter the impact of A1c on initiation of antihyperglycemic therapy. When using A1c values as a predictor variable, a simple imputation algorithm based only on age, sex, and fasting plasma glucose gave acceptable results.

Endocrine pancreatic function changes after acute pancreatitis.

Science.gov (United States)

Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

2011-10-01

This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

The Effect of Resistance Training on Cardio-Metabolic Factors in Males with Type 2 Diabetes

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Ghalavand

2014-10-01

Full Text Available Background Diabetes is one of the most important metabolic diseases in the world and exercise is a common advice to manage diabetes and reduce its complications. Objectives The aim of this study was to investigate the effect of resistance training on blood glucose, blood pressure and resting heart rate in males with type 2 diabetes. Materials and Methods In this semi-experimental study, 20 males with type 2 diabetes with mean age of 46 ± 3.4 years old who met the inclusion criteria were selected. The participants were randomly assigned into resistance training (n = 10 and control (n = 10 groups. Resistance exercise training program was performed for eight weeks, three sessions per week. Cardiovascular and biochemical parameters were measured before and after the intervention. To analyze the measured parameters changes t-test was used at P ≤ 0.05 significance level. Results After eight weeks, a significant decrease in fasting blood sugar (P = 0.002, glycosylated hemoglobin (P = 0.025 and systolic blood pressure (P = 0.022 was observed in the resistance group. In addition, there was a significant difference in blood sugar (P = 0.003 and glycosylated hemoglobin (P = 0.031 between the two groups. Conclusions Findings of this study confirmed the positive influence of resistance training to control blood glucose and blood pressure in males with type 2 diabetes.

Glycosylation of the self-recognizing Escherichia coli Ag43 autotransporter protein

DEFF Research Database (Denmark)

Sherlock, O.; Dobrindt, U.; Jensen, J.B.

2006-01-01

a novel member to this exclusive group, namely, antigen 43 (Ag43), a self-recognizing autotransporter protein. By mass spectrometry Ag43 was demonstrated to be glycosylated by addition of heptose residues at several positions in the passenger domain. Glycosylation of Ag43 by the action of the Aah and Tib......C glycosyltransferases was observed in laboratory strains. Importantly, Ag43 was also found to be glycosylated in a wild-type strain, suggesting that Ag43-glycosylation may be a widespread phenomenon. Glycosylation of Ag43 does not seem to interfere with its self-associating properties. However, the glycosylated form...

Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

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de Jongh, Harmen H. J.; Robles, Carlos López; Nordlee, Julie A.; Lee, Poi-Wah; Baumert, Joseph L.; Hamilton, Robert G.; Taylor, Steve L.; Koppelman, Stef J.

2013-01-01

Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein's digestibility is not affected by such processing. PMID:23878817

Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

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Harmen H. J. de Jongh

2013-01-01

Full Text Available Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa, the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein’s digestibility is not affected by such processing.

Functional Analysis of Glycosylation of Zika Virus Envelope Protein

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Camila R. Fontes-Garfias

2017-10-01

Full Text Available Summary: Zika virus (ZIKV infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E protein is responsible for viral entry and represents a major determinant for viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts. : Zika virus (ZIKV causes devastating congenital abnormities and Guillain-Barré syndrome. Fontes-Garfias et al. showed that the glycosylation of ZIKV envelope protein plays an important role in infecting mosquito vectors and pathogenesis in mouse. Keywords: Zika virus, glycosylation, flavivirus entry, mosquito transmission, vaccine

Toward stable genetic engineering of human o-glycosylation in plants

DEFF Research Database (Denmark)

Yang, Zhang; Bennett, Eric Paul; Jørgensen, Bodil

2012-01-01

Glycosylation is the most abundant and complex posttranslational modification to be considered for recombinant production of therapeutic proteins. Mucin-type (N-acetylgalactosamine [GalNAc]-type) O-glycosylation is found in eumetazoan cells but absent in plants and yeast, making these cell types...... an obvious choice for de novo engineering of this O-glycosylation pathway. We previously showed that transient implementation of O-glycosylation capacity in plants requires introduction of the synthesis of the donor substrate UDP-GalNAc and one or more polypeptide GalNAc-transferases for incorporating Gal......NAc residues into proteins. Here, we have stably engineered O-glycosylation capacity in two plant cell systems, soil-grown Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum) Bright Yellow-2 suspension culture cells. Efficient GalNAc O-glycosylation of two stably coexpressed substrate O...

Cloning, expression and characterization of a mammalian Nudix hydrolase-like enzyme that cleaves the pyrophosphate bond of UDP-glucose.

OpenAIRE

Yagi, Toshihiro; Baroja-Fernández, Edurne; Yamamoto, Ryuji; Muñoz, Francisco José; Akazawa, Takashi; Hong, Kyoung Su; Pozueta-Romero, Javier

2003-01-01

A distinct UDP-glucose (UDPG) pyrophosphatase (UGPPase, EC 3.6.1.45) has been characterized using pig kidney ( Sus scrofa ). This enzyme hydrolyses UDPG, the precursor molecule of numerous glycosylation reactions in animals, to produce glucose 1-phosphate (G1P) and UMP. Sequence analyses of the purified enzyme revealed that, similar to the case of a nucleotide-sugar hydrolase controlling the intracellular levels of ADP-glucose linked to glycogen biosynthesis in Escherichia coli [Moreno-Bruna,...

诺和锐30联合茵陈蒿汤加减方治疗慢性乙型肝炎合并糖尿病的疗效分析

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LIU Hongxia

2014-04-01

Full Text Available ObjectiveTo investigate the treatment methods for chronic hepatitis B (CHB with diabetes. MethodsSixty-eight patients with CHB accompanied by diabetes who were hospitalized in the division of infectious diseases of our hospital from January 2008 to December 2012 were included in the study. These patients were divided into treatment group (n=41 and control group (n=27 based on treatment methods. In addition to conventional liver protection treatment, NovoRapid 30 was given to the control group, while NovoRapid 30 combined with modified Yinchenhao decoction were given to the treatment group. During treatment, liver function, blood glucose levels, and glycosylated hemoglobin levels were monitored periodically; liver function recovery time was analyzed statistically; the incidence of hypoglycemia for each patient and daily dose of insulin were recorded and analyzed statistically. Before-after comparison and between-group comparison of means were made by t test. ResultsAfter treatment, both groups showed a significant improvement in liver function (P＜0.01 and significant decreases in blood glucose and glycosylated hemoglobin levels (P＜0.01; the treatment group had a significantly lower glycosylated hemoglobin level than the control group (6.3%±0.6% vs 7.3%±0.5%, t=7.46, P＜0.01. Compared with the control group, the treatment group had a significantly shorter liver function recovery time (28.7±5.61 days vs 35.5±6.33 days, t=4.53, P＜0.01, a significantly lower incidence of hypoglycemia (0.8±0.3 times/patient vs 2.2±0.8 times/patient, t=8.78, P＜0.01, and a significantly lower daily dose of insulin (37.4±5.2 U vs 44.6±6.5 U, t=4.86, P＜0.01. ConclusionCombination therapy with NovoRapid and modified Yinchenhao decoction is an effective, safe, and economical approach to the treatment of CHB with diabetes

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses--A Case-Control Study.

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Gao, Ting; Jin, Kairui; Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. A total of 460 permanent residents of the Fengxian District, aged 40-60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18-28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism.

Correlation between Glycated Hemoglobin and Triglyceride Level in Type 2 Diabetes Mellitus.

Science.gov (United States)

Naqvi, Syeda; Naveed, Shabnam; Ali, Zeeshan; Ahmad, Syed Masroor; Asadullah Khan, Raad; Raj, Honey; Shariff, Shoaib; Rupareliya, Chintan; Zahra, Fatima; Khan, Saba

2017-06-13

Dyslipidemia is quite prevalent in non-insulin dependent diabetes mellitus. Maintaining tight glycemic along with lipid control plays an essential role in preventing micro- and macro-vascular complications associated with diabetes. The main purpose of the study was to highlight the relationship between glycosylated hemoglobin (HbA1c) and triglyceride levels. This may in turn help in predicting the triglyceride status of type 2 diabetics and therefore identifying patients at increased risk from cardiovascular events. Hypertriglyceridemia is one of the common risk factors for coronary artery disease in type 2 diabetes mellitus (DM). Careful monitoring of the blood glucose level can be used to predict lipid status and can prevent most of the complications associated with the disease. This is a cross-sectional study using data collected from the outpatient diabetic clinic of Jinnah Postgraduate Medical Centre (JPMC) Karachi, Pakistan. Patients of age 18 years and above were recruited from the clinic. A total of consenting 509 patients of type 2 diabetes mellitus were enrolled over a period of 11 months.  For statistical analysis, SPSS Statistics for Windows, Version 17.0 ( IBM Corp, Armonk, New York) was used and Chi-square and Pearson's correlation coefficient was used to find the association between triglyceride and HbA1c. The HbA1c was dichotomized into four groups on the basis of cut-off. Chi-square was used for association between HbA1c with various cut-off values and high triglyceride levels. Odds-ratio and its 95% confidence interval were calculated to estimate the level of risk between high triglyceride levels and HbA1c groups. The p-value triglyceride was evaluated in four different groups of HbA1c, with a cut-off seven, eight, nine and 10 respectively. With HbA1c cut-off value of 7%, 74% patients had high triglycerides and showed a significant association with high triglyceride levels at p index, lifestyle) and health status factors (blood pressure

Trans-species Engineering of Glycosylated Therapeutic Proteins

DEFF Research Database (Denmark)

Yang, Zhang

eukaryotes and even prokaryotes. Insect and yeast cells produce O-glycosylation incompatible with use in humans, however recently the yeast Pichia was engineered to perform the first step of human-like O-glycosylation. This review provides an overview of past and current engineering efforts of N...

Radioimmunochemical characterization of hemoglobins Lepore and Kenya: unique antigenic determinants located on hybrid hemoglobins

International Nuclear Information System (INIS)

Garver, F.A.; Altay, G.; Baker, M.M.; Gravely, M.; Huisman, T.H.J.

1978-01-01

Antisera were produced in rabbits to the three known types of Lepore hemoglobins, which contain hybrid delta-β non-α-chains, and to hemoglobin Kenya, which has a hybrid γ-β non-α-chain. By using a sensitive radioimmunoassay technique, the absorbed antisera were shown to contain an antibody population that was specific for the hybrid hemoglobin and did not cross-react with normal hemoglobins. However, with the absorbed Lepore-specific antisera, the three known types of Lepore hemoglobins were antigenically indistinguishable from each other, suggesting that antibodies are not produced to the primary structural differences which define the three non-α-chains of the Lepore hemoglobins. These studies demonstrate that the non-α-subunits of hemoglobins Lepore and Kenya possess unique antigenic determinant sites, evidently resulting from an altered polypeptide conformation

Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients

OpenAIRE

Huang, Rong; Han, Jing; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Shaohua

2017-01-01

Background and aims People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients. Results In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghre...

Similarities and Differences in the Glycosylation Mechanisms in Prokaryotes and Eukaryotes

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Anne Dell

2010-01-01

Full Text Available Recent years have witnessed a rapid growth in the number and diversity of prokaryotic proteins shown to carry N- and/or O-glycans, with protein glycosylation now considered as fundamental to the biology of these organisms as it is in eukaryotic systems. This article overviews the major glycosylation pathways that are known to exist in eukarya, bacteria and archaea. These are (i oligosaccharyltransferase (OST-mediated N-glycosylation which is abundant in eukarya and archaea, but is restricted to a limited range of bacteria; (ii stepwise cytoplasmic N-glycosylation that has so far only been confirmed in the bacterial domain; (iii OST-mediated O-glycosylation which appears to be characteristic of bacteria; and (iv stepwise O-glycosylation which is common in eukarya and bacteria. A key aim of the review is to integrate information from the three domains of life in order to highlight commonalities in glycosylation processes. We show how the OST-mediated N- and O-glycosylation pathways share cytoplasmic assembly of lipid-linked oligosaccharides, flipping across the ER/periplasmic/cytoplasmic membranes, and transferring “en bloc” to the protein acceptor. Moreover these hallmarks are mirrored in lipopolysaccharide biosynthesis. Like in eukaryotes, stepwise O-glycosylation occurs on diverse bacterial proteins including flagellins, adhesins, autotransporters and lipoproteins, with O-glycosylation chain extension often coupled with secretory mechanisms.

Sucrose synthase: A unique glycosyltransferase for biocatalytic glycosylation process development.

Science.gov (United States)

Schmölzer, Katharina; Gutmann, Alexander; Diricks, Margo; Desmet, Tom; Nidetzky, Bernd

2016-01-01

Sucrose synthase (SuSy, EC 2.4.1.13) is a glycosyltransferase (GT) long known from plants and more recently discovered in bacteria. The enzyme catalyzes the reversible transfer of a glucosyl moiety between fructose and a nucleoside diphosphate (NDP) (sucrose+NDP↔NDP-glucose+fructose). The equilibrium for sucrose conversion is pH dependent, and pH values between 5.5 and 7.5 promote NDP-glucose formation. The conversion of a bulk chemical to high-priced NDP-glucose in a one-step reaction provides the key aspect for industrial interest. NDP-sugars are important as such and as key intermediates for glycosylation reactions by highly selective Leloir GTs. SuSy has gained renewed interest as industrially attractive biocatalyst, due to substantial scientific progresses achieved in the last few years. These include biochemical characterization of bacterial SuSys, overproduction of recombinant SuSys, structural information useful for design of tailor-made catalysts, and development of one-pot SuSy-GT cascade reactions for production of several relevant glycosides. These advances could pave the way for the application of Leloir GTs to be used in cost-effective processes. This review provides a framework for application requirements, focusing on catalytic properties, heterologous enzyme production and reaction engineering. The potential of SuSy biocatalysis will be presented based on various biotechnological applications: NDP-sugar synthesis; sucrose analog synthesis; glycoside synthesis by SuSy-GT cascade reactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Glycosylation of the N-terminal potential N-glycosylation sites in the human α1,3-fucosyltransferase V and -VI (hFucTV and -VI)

DEFF Research Database (Denmark)

Christensen, Lise Lotte; Bross, Peter Gerd; Ørntoft, Torben Falck

2000-01-01

Human alpha1,3-fucosyltransferase V and -VI (hFucTV and -VI) each contain four potential N-glycosylation sites (hFucTV: Asn60, Asn105, Asn167 and Asn198 and hFucTVI: Asn46, Asn91, Asn153 and Asn184). Glycosylation of the two N-terminal potential N-glycosylation sites (hFucTV: Asn60, Asn105 and h......FucTVI: Asn46 and Asn91) have never been studied in detail. In the present study, we have analysed the glycosylation of these potential N-glycosylation sites. Initially, we compared the molecular mass of hFucTV and -VI expressed in COS-7 cells treated with tunicamycin with the mass of the proteins...... in untreated cells. The difference in molecular mass between the proteins in treated and untreated cells corresponded to the presence of at least three N-linked glycans. We then made a series of mutants, in which the asparagine residues in the N-terminal potential N-glycosylation sites were replaced...

Diversity and functions of protein glycosylation in insects.

Science.gov (United States)

Walski, Tomasz; De Schutter, Kristof; Van Damme, Els J M; Smagghe, Guy

2017-04-01

The majority of proteins is modified with carbohydrate structures. This modification, called glycosylation, was shown to be crucial for protein folding, stability and subcellular location, as well as protein-protein interactions, recognition and signaling. Protein glycosylation is involved in multiple physiological processes, including embryonic development, growth, circadian rhythms, cell attachment as well as maintenance of organ structure, immunity and fertility. Although the general principles of glycosylation are similar among eukaryotic organisms, insects synthesize a distinct repertoire of glycan structures compared to plants and vertebrates. Consequently, a number of unique insect glycans mediate functions specific to this class of invertebrates. For instance, the core α1,3-fucosylation of N-glycans is absent in vertebrates, while in insects this modification is crucial for the development of wings and the nervous system. At present, most of the data on insect glycobiology comes from research in Drosophila. Yet, progressively more information on the glycan structures and the importance of glycosylation in other insects like beetles, caterpillars, aphids and bees is becoming available. This review gives a summary of the current knowledge and recent progress related to glycan diversity and function(s) of protein glycosylation in insects. We focus on N- and O-glycosylation, their synthesis, physiological role(s), as well as the molecular and biochemical basis of these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Blood Glucose Levels in Diabetic Patients Following Corticosteroid Injections into the Subacromial Space of the Shoulder.

Science.gov (United States)

Aleem, Alexander W; Syed, Usman Ali M; Nicholson, Thema; Getz, Charles L; Namdari, Surena; Beredjiklian, Pedro K; Abboud, Joseph A

2017-09-01

Corticosteroid injections are used to treat a variety of orthopedic conditions with the goal of decreasing pain and inflammation. Administration of systemic or local corticosteroids risks temporarily increasing blood glucose levels, especially diabetic patients. The purpose of this study is to quantify the effects of corticosteroid injections on blood glucose levels in diabetic patients with shoulder pathology. Diabetic patients who regularly monitored their blood glucose levels and were indicated for a subacromial corticosteroid injection were included in this prospective investigation. The typical normal morning fasting glucose and most recent hemoglobin A1c level was recorded for each patient. After injection, patients were contacted daily to confirm their fasting morning glucose level for 10 days post-injection. Seventeen consecutive patients were enrolled. Patients with hemoglobin A1c of patients' glucose levels returned to near baseline levels around post-injection day 8, while poorly controlled patients levels remained elevated. Similarly, insulin-dependent diabetic patients had an average increase in fasting glucose level of 99 mg/dL versus 50 mg/dL in non-insulin-dependent diabetic patients ( P patients with well-controlled diabetes experience smaller elevations and faster return to baseline glucose levels than patients with poor control. Insulin dependent diabetics experienced similar findings as patients with poor control. Future studies are needed to evaluate dosing to optimize the risks of blood glucose elevation while maintaining therapeutic benefit.

Timing of hypertonic glucose and thermochemotherapy with 1-(4-amino-2-methylpyrimidine-5-yl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in the BT4An rat glioma: relation to intratumoral pH reduction and circulatory changes after glucose supply

International Nuclear Information System (INIS)

Schem, Baard-Christian; Roszinski, Stefan; Krossnes, Baard Kronen; Mella, Olav

1995-01-01

Purpose: Intraperitoneal hypertonic glucose has previously been shown to induce hyperglycemia, hemoconcentration, and to influence systemic and tumor circulation, and, thus, enhance the effect of thermochemotherapy with 1-(4-amino-2-methylpyrimidine-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). However, the optimal timing and the precise mechanisms responsible are not known. The effect of different time intervals between glucose load and thermochemotherapy with ACNU in the treatment of BT 4 An tumors, therefore, was investigated. Changes of serum glucose (Se-glucose), hemoglobin, systemic circulation parameters, tumor pH, and tumor temperature, induced by intraperitoneal glucose and/or hyperthermia, were measured to assess their effect on tumor growth. Methods and Materials: (a): Inbred BD IX rats with BT 4 An tumors on the hind leg were treated with ACNU 7 mg/kg intravenously just before waterbath hyperthermia, and intraperitoneal hypertonic glucose (6 g/kg) at different time intervals before (240-0 min) or immediately after thermochemotherapy. (b): Intratumoral pH and temperature were measured at different intervals after intraperitoneal glucose, and during hyperthermia with or without previous glucose. (c): Hemoglobin, hematocrit, and Se-glucose were measured at different times after intraperitoneal glucose. (d): Mean arterial pressure, pulse pressure, and heart rate were measured for 120 min after intraperitoneal glucose. Results: (a): The number of tumor controls and the growth delay was greatest with glucose 45 min before thermochemotherapy, and least with a time interval of 240 min. Glucose after thermochemotherapy delayed tumor growth. (b): After intraperitoneal glucose alone, intratumoral pH decreased gradually from 6.76 to 5.86 after 240 min. Hyperthermia 120 min after glucose induced a rapid further pH drop, while hyperthermia alone had no significant influence on pH. Intratumoral temperature was

Fish hemoglobins

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P.C. de Souza

2007-06-01

Full Text Available Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemical strategies to adapt to the changing environmental gas availability. Structurally, most fish hemoglobins are tetrameric; however, those from some species such as lamprey and hagfish dissociate, being monomeric when oxygenated and oligomeric when deoxygenated. Fish blood frequently possesses several hemoglobins; the primary origin of this finding lies in the polymorphism that occurs in the globin loci, an aspect that may occasionally confer advantages to its carriers or even be a harmless evolutionary remnant. On the other hand, the functional properties exhibit different behaviors, ranging from a total absence of responses to allosteric regulation to drastic ones, such as the Root effect.

A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index.

Science.gov (United States)

Kim, Ho Jin; Moon, Jun Sung; Park, Il Rae; Kim, Joong Hee; Yoon, Ji Sung; Won, Kyu Chang; Lee, Hyoung Woo

2017-09-01

Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance. This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was 'ln [FPG (mg/dL)×triglyceride (mg/dL)/2],' and the sCD36 index was 'ln [sCD36 (pg/mL)×FPG (mg/dL)/2].' One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; Pindex for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment. sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes. Copyright © 2017 Korean Endocrine Society

O-GlcNAc-specific antibody CTD110.6 cross-reacts with N-GlcNAc2-modified proteins induced under glucose deprivation.

Directory of Open Access Journals (Sweden)

Takahiro Isono

Full Text Available Modification of serine and threonine residues in proteins by O-linked β-N-acetylglucosamine (O-GlcNAc glycosylation is a feature of many cellular responses to the nutritional state and to stress. O-GlcNAc modification is reversibly regulated by O-linked β-N-acetylglucosamine transferase (OGT and β-D-N-acetylglucosaminase (O-GlcNAcase. O-GlcNAc modification of proteins is dependent on the concentration of uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc, which is a substrate of OGT and is synthesized via the hexosamine biosynthetic pathway. Immunoblot analysis using the O-GlcNAc-specific antibody CTD110.6 has indicated that glucose deprivation increases protein O-GlcNAcylation in some cancer cells. The mechanism of this paradoxical phenomenon has remained unclear. Here we show that the increased glycosylation induced by glucose deprivation and detected by CTD110.6 antibodies is actually modification by N-GlcNAc(2, rather than by O-GlcNAc. We found that this induced glycosylation was not regulated by OGT and O-GlcNAcase, unlike typical O-GlcNAcylation, and it was inhibited by treatment with tunicamycin, an N-glycosylation inhibitor. Proteomics analysis showed that proteins modified by this induced glycosylation were N-GlcNAc(2-modified glycoproteins. Furthermore, CTD110.6 antibodies reacted with N-GlcNAc(2-modified glycoproteins produced by a yeast strain with a ts-mutant of ALG1 that could not add a mannose residue to dolichol-PP-GlcNAc(2. Our results demonstrated that N-GlcNAc(2-modified glycoproteins were induced under glucose deprivation and that they cross-reacted with the O-GlcNAc-specific antibody CTD110.6. We therefore propose that the glycosylation status of proteins previously classified as O-GlcNAc-modified proteins according to their reactivity with CTD110.6 antibodies must be re-examined. We also suggest that the repression of mature N-linked glycoproteins due to increased levels of N-GlcNAc(2-modified proteins is a newly

Glycosylation in HIV-1 envelope glycoprotein and its biological implications

KAUST Repository

Ho, Yung Shwen

2013-08-01

Glycosylation of HIV-1 envelope proteins (Env gp120/gp41) plays a vital role in viral evasion from the host immune response, which occurs through the masking of key neutralization epitopes and the presentation of the Env glycosylation as \\'self\\' to the host immune system. Env glycosylation is generally conserved, yet its continual evolution plays an important role in modulating viral infectivity and Env immunogenicity. Thus, it is believed that Env glycosylation, which is a vital part of the HIV-1 architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may assist in effectively designing Env-based immunogens and in clearly understanding HIV vaccines. This review provides an in-depth perspective of various aspects of Env glycosylation in the context of HIV-1 pathogenesis. © 2013 Future Medicine Ltd.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in a stepwise fashion to detect undiagnosed diabetes mellitus.

Science.gov (United States)

Nakagami, Tomoko; Tominaga, Makoto; Nishimura, Rimei; Daimon, Makoto; Oizumi, Toshihide; Yoshiike, Nobuo; Tajima, Naoko

2007-09-01

Type 2 diabetes mellitus (DM) is a common and serious condition related with considerable morbidity. Screening for DM is one strategy for reducing this burden. In Japan National Diabetes Screening Program (JNDSP) guideline, the combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) in a stepwise fashion has been recommended to identify the group of people needing life-style counseling or medical care. However, the efficacy of this program has not been fully evaluated, as an oral glucose tolerance test (OGTT) is not mandatory in the guideline. The aim of this study was to assess the validity of the screening test scenario, in which an OGTT would be applied to people needing life-style counseling or medical care on this guideline: FPG 110-125 mg/dl and HbA1c over 5.5%. Subjects were 1,726 inhabitants without a previous history of DM in the Funagata study, which is a population-based survey conducted in Yamagata prefecture to clarify the risk factors, related conditions, and consequences of DM. DM was diagnosed according to the 1999 World Health Organization criteria. The prevalence of undiagnosed DM was 6.6%. The tested screening scenario gave a sensitivity of 55.3%, a specificity of 98.4%, a positive predictive value of 70.8%, and a negative predictive value of 96.9% for undiagnosed DM. In conclusion, the screening test scenario, in which an OGTT would be followed by the combined use of FPG and HbA1c in a stepwise fashion according to the JNDSP guideline, was not effective in identifying people with undiagnosed DM.

Functional Analysis of Glycosylation of Zika Virus Envelope Protein.

Science.gov (United States)

Fontes-Garfias, Camila R; Shan, Chao; Luo, Huanle; Muruato, Antonio E; Medeiros, Daniele B A; Mays, Elizabeth; Xie, Xuping; Zou, Jing; Roundy, Christopher M; Wakamiya, Maki; Rossi, Shannan L; Wang, Tian; Weaver, Scott C; Shi, Pei-Yong

2017-10-31

Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E) protein is responsible for viral entry and represents a major determinant for viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program.

Science.gov (United States)

Silva, Marcilene Rezende; Sendin, Shimene Mascarenhas; Araujo, Isabela Couto de Oliveira; Pimentel, Fernanda Silva; Viana, Marcos Borato

2013-01-01

To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. β(S) allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. THE FOLLOWING ALPHA CHAIN VARIANTS WERE FOUND: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

Detection of Sickle Cell Hemoglobin in Haiti by Genotyping and Hemoglobin Solubility Tests

Science.gov (United States)

Carter, Tamar E.; von Fricken, Michael; Romain, Jean R.; Memnon, Gladys; St. Victor, Yves; Schick, Laura; Okech, Bernard A.; Mulligan, Connie J.

2014-01-01

Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in suboptimal screening settings like Haiti. PMID:24957539

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses—A Case-Control Study

Science.gov (United States)

Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Purpose Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. Methods A total of 460 permanent residents of the Fengxian District, aged 40–60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18–28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Results Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Conclusions Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism. PMID:26247824

Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy

Science.gov (United States)

Nair, Anil V.; Hocher, Berthold; Verkaart, Sjoerd; van Zeeland, Femke; Pfab, Thiemo; Slowinski, Torsten; Chen, You-Peng; Schlingmann, Karl Peter; Schaller, André; Gallati, Sabina; Bindels, René J.; Konrad, Martin; Hoenderop, Joost G.

2012-01-01

Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 (V1393I, K1584E) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6(V1393I) and TRPM6(K1584E), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T1391) and TRPM6(S1583). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6(V1393I) and TRPM6(K1584E) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6(V1393I) and TRPM6(K1584E) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6. PMID:22733750

Importance of N-Glycosylation on CD147 for Its Biological Functions

Science.gov (United States)

Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

2014-01-01

Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation. PMID:24739808

Importance of N-Glycosylation on CD147 for Its Biological Functions

Directory of Open Access Journals (Sweden)

Yang Bai

2014-04-01

Full Text Available Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

Directory of Open Access Journals (Sweden)

Marcilene Rezende Silva

2013-01-01

Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes

Directory of Open Access Journals (Sweden)

Kim Y

2012-08-01

Full Text Available Yoojin Kim, Ambika R BabuDivision of Endocrinology, John Stroger Jr Hospital of Cook County and Rush University, Chicago, IL, USABackground: The kidney plays an important role in glucose metabolism, and has been considered a target for therapeutic intervention. The sodium-glucose cotransporter type 2 (SGLT2 mediates most of the glucose reabsorption from the proximal renal tubule. Inhibition of SGLT2 leads to glucosuria and provides a unique mechanism to lower elevated blood glucose levels in diabetes. The purpose of this review is to explore the physiology of SGLT2 and discuss several SGLT2 inhibitors which have clinical data in patients with type 2 diabetes.Methods: We performed a PubMed search using the terms "SGLT2" and "SGLT2 inhibitor" through April 10, 2012. Published articles, press releases, and abstracts presented at national and international meetings were considered.Results: SGLT2 inhibitors correct a novel pathophysiological defect, have an insulin-independent action, are efficacious with glycosylated hemoglobin reduction ranging from 0.5% to 1.5%, promote weight loss, have a low incidence of hypoglycemia, complement the action of other antidiabetic agents, and can be used at any stage of diabetes. They are generally well tolerated. However, due to side effects, such as repeated urinary tract and genital infections, increased hematocrit, and decreased blood pressure, appropriate patient selection for drug initiation and close monitoring after initiation will be important. Results of ongoing clinical studies of the effect of SGLT2 inhibitors on diabetic complications and cardiovascular safety are crucial to determine the risk-benefit ratio. A recent decision by the Committee for Medicinal Products for Human Use of the European Medicines Agency has recommended approval of dapagliflozin for the treatment of type 2 diabetes as an adjunct to diet and exercise, in combination with other glucose-lowering medicinal products, including

Links between CD147 Function, Glycosylation, and Caveolin-1

OpenAIRE

Tang, Wei; Chang, Sharon B.; Hemler, Martin E.

2004-01-01

Cell surface CD147 shows remarkable variations in size (31-65 kDa) because of heterogeneous N-glycosylation, with the most highly glycosylated forms functioning to induce matrix metalloproteinase (MMP) production. Here we show that all three CD147 N-glycosylation sites make similar contributions to both high and low glycoforms (HG- and LG-CD147). l-Phytohemagglutinin lectin binding and swainsonine inhibition experiments indicated that HG-CD147 contains N-acetylglucosaminyltransferase V-cataly...

The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients

DEFF Research Database (Denmark)

Balas, Bogdan; Baig, Muhammad R; Watson, Catherine

2007-01-01

AIMS/HYPOTHESIS: Vildagliptin is a selective dipeptidyl peptidase IV inhibitor that augments meal-stimulated levels of biologically active glucagon-like peptide-1. Chronic vildagliptin treatment decreases postprandial glucose levels and reduces hemoglobin A1c in type 2 diabetic patients. However......, little is known about the mechanism(s) by which vildagliptin promotes reduction in plasma glucose concentration. METHODS: Sixteen patients with type 2 diabetes (age, 48+/-3 yr; body mass index, 34.4+/-1.7 kg/m2; hemoglobin A1c, 9.0+/-0.3%) participated in a randomized, double-blind, placebo......-controlled trial. On separate days patients received 100 mg vildagliptin or placebo at 1730 h followed 30 min later by a meal tolerance test (MTT) performed with double tracer technique (3-(3)H-glucose iv and 1-(14)C-glucose orally). RESULTS: After vildagliptin, suppression of endogenous glucose production (EGP...

The effect of an inhaled corticosteroid on glucose control in type 2 diabetes.

LENUS (Irish Health Repository)

Faul, John L

2009-06-01

OBJECTIVE: To determine the effect of inhaled corticosteroid (ICS) therapy on glucose control in adults with type 2 diabetes mellitus and coexisting asthma or chronic obstructive pulmonary disease (COPD). DESIGN: A prospective randomized, double-blind, double-dummy placebo-controlled, crossover investigation of inhaled steroids and oral leukotriene blockers. SETTING: A United States Department of Veterans Affairs Health Care System outpatient setting. PARTICIPANTS: Adults with type 2 diabetes and asthma or COPD. METHODS: Subjects (n=12) were randomized to receive either inhaled fluticasone propionate (440 microg twice daily) and oral placebo, or inhaled placebo and oral montelukast (10 mg\\/day). After 6 weeks, subjects were switched to the opposite therapy for 6 weeks. The primary outcome measure was the change in the percentage of glycosylated hemoglobin (%HbA1c) at 6 weeks relative to the baseline value. RESULTS: Ten patients completed the study. The difference between the mean within-subject changes in %HbA1c associated with 6-week periods of fluticasone and the mean changes associated with montelukast therapy was small but statistically significant (mean difference=0.25; P<0.025). Neither fluticasone nor oral montelukast therapy for 6 weeks led to a significantly different mean % HbA1c compared with the relevant baseline (mean differences=0.11 and -0.14, respectively). CONCLUSION: The absence of a clinically significant within-subject difference in the changes in %HbA1c associated with fluticasone versus oral montelukast therapy, or between either therapy or baseline does not warrant recommending changes in therapy for asthma or diabetes in patients with these co-morbid conditions. However, we suggest that clinicians carefully monitor blood glucose control when diabetic patients initiate ICS, especially with higher dosages.

Hemoglobin Wayne Trait with Incidental Polycythemia.

Science.gov (United States)

Ambelil, Manju; Nguyen, Nghia; Dasgupta, Amitava; Risin, Semyon; Wahed, Amer

2017-01-01

Hemoglobinopathies, caused by mutations in the globin genes, are one of the most common inherited disorders. Many of the hemoglobin variants can be identified by hemoglobin analysis using conventional electrophoresis and high performance liquid chromatography; however hemoglobin DNA analysis may be necessary in other cases for confirmation. Here, we report a case of a rare alpha chain hemoglobin variant, hemoglobin Wayne, in a 47-year-old man who presented with secondary polycythemia. Capillary zone electrophoresis and high performance liquid chromatography revealed a significant amount of a hemoglobin variant, which was further confirmed by hemoglobin DNA sequencing as hemoglobin Wayne. Since the patient was not homozygous for hemoglobin Wayne, which is associated with secondary polycythemia, the laboratory diagnosis in this case was critical in ruling out hemoglobinopathy as the etiology of his polycythemia. © 2017 by the Association of Clinical Scientists, Inc.

N-linked glycosylation of the immunoglobulin variable region

NARCIS (Netherlands)

van de Bovenkamp, Fleur S.; Derksen, Ninotska I. L.; Ooijevaar-de Heer, Pleuni; van Schie, Karin A.; Kruithof, Simone; Berkowska, Magdalena A.; van der Schoot, C. Ellen; Ijspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E. M.; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S. Marieke; Vidarsson, Gestur; Rispens, Theo

2018-01-01

N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we

The Hemoglobin E Thalassemias

Science.gov (United States)

Fucharoen, Suthat; Weatherall, David J.

2012-01-01

Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of β thalassemia. Its interactions with different forms of α thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with β thalassemia, a condition called hemoglobin E β thalassemia, is by far the most common severe form of β thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe β-thalassemia disorders. PMID:22908199

[The role of protein glycosylation in immune system].

Science.gov (United States)

Ząbczyńska, Marta; Pocheć, Ewa

2015-01-01

Glycosylation is one of the most frequent post-translational modifications of proteins. The majority of cell surface and secreted proteins involved in immune response is glycosylated. The structural diversity of glycans depends on monosaccharide composition, type of glycosidic linkage and branching. These structural modifications determine a great variability of glycoproteins. The oligosaccharide components of proteins are regulated mostly by expression of glycosyltransferases and glycosidases and many environmental factors. Glycosylation influences the function of all immune cells. Glycans play a crucial role in intercellular contacts and leukocytes migration. These interactions are important in activation and proliferation of leukocytes and during immune response. The key immune proteins, such as TCR, MHC, TLR and antibodies are glycosylated. Sugars on the surface of pathogens and self-surface glycoproteins are recognized by special carbohydrate binding proteins called lectins. Changes of glycan structure are common in many pathological processes occurring in immune system, therefore they are used as molecular markers of different diseases.

Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.

Science.gov (United States)

Eklund, Erik A; Merbouh, Nabyl; Ichikawa, Mie; Nishikawa, Atsushi; Clima, Jessica M; Dorman, James A; Norberg, Thomas; Freeze, Hudson H

2005-11-01

Patients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients.

Effect of varying concentrations of orally ingested glucose on platelet ...

African Journals Online (AJOL)

The physiologic basis of bleeding is a function of normal platelets and coagulation factors. This study is aimed at ascertaining the effect of varying concentrations of orally ingested glucose on platelet count and hemoglobin concentration during menstruation. Forty menstruating students between the ages of 18 and 25 from ...

Phylogeny of Echinoderm Hemoglobins.

Directory of Open Access Journals (Sweden)

Ana B Christensen

Full Text Available Recent genomic information has revealed that neuroglobin and cytoglobin are the two principal lineages of vertebrate hemoglobins, with the latter encompassing the familiar myoglobin and α-globin/β-globin tetramer hemoglobin, and several minor groups. In contrast, very little is known about hemoglobins in echinoderms, a phylum of exclusively marine organisms closely related to vertebrates, beyond the presence of coelomic hemoglobins in sea cucumbers and brittle stars. We identified about 50 hemoglobins in sea urchin, starfish and sea cucumber genomes and transcriptomes, and used Bayesian inference to carry out a molecular phylogenetic analysis of their relationship to vertebrate sequences, specifically, to assess the hypothesis that the neuroglobin and cytoglobin lineages are also present in echinoderms.The genome of the sea urchin Strongylocentrotus purpuratus encodes several hemoglobins, including a unique chimeric 14-domain globin, 2 androglobin isoforms and a unique single androglobin domain protein. Other strongylocentrotid genomes appear to have similar repertoires of globin genes. We carried out molecular phylogenetic analyses of 52 hemoglobins identified in sea urchin, brittle star and sea cucumber genomes and transcriptomes, using different multiple sequence alignment methods coupled with Bayesian and maximum likelihood approaches. The results demonstrate that there are two major globin lineages in echinoderms, which are related to the vertebrate neuroglobin and cytoglobin lineages. Furthermore, the brittle star and sea cucumber coelomic hemoglobins appear to have evolved independently from the cytoglobin lineage, similar to the evolution of erythroid oxygen binding globins in cyclostomes and vertebrates.The presence of echinoderm globins related to the vertebrate neuroglobin and cytoglobin lineages suggests that the split between neuroglobins and cytoglobins occurred in the deuterostome ancestor shared by echinoderms and vertebrates.

Prion propagation in cells expressing PrP glycosylation mutants.

Science.gov (United States)

Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-04-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

Unusual glycosylation of proteins: Beyond the universal sequon and other amino acids.

Science.gov (United States)

Dutta, Devawati; Mandal, Chhabinath; Mandal, Chitra

2017-12-01

Glycosylation of proteins is the most common, multifaceted co- and post-translational modification responsible for many biological processes and cellular functions. Significant alterations and aberrations of these processes are related to various pathological conditions, and often turn out to be disease biomarkers. Conventional N-glycosylation occurs through the recognition of the consensus sequon, asparagine (Asn)-X-serine (Ser)/threonine (Thr), where X is any amino acid except for proline, with N-acetylglucosamine (GlcNAc) as the first glycosidic linkage. Usually, O-glycosylation adds a glycan to the hydroxyl group of Ser or Thr beginning with N-acetylgalactosamine (GalNAc). Protein glycosylation is further governed by additional diversifications in sequon and structure, which are yet to be fully explored. This review mainly focuses on the occurrence of N-glycosylation in non-consensus motifs, where Ser/Thr at the +2 position is substituted by other amino acids. Additionally, N-glycosylation is also observed in other amide/amine group-containing amino acids. Similarly, O-glycosylation occurs at hydroxyl group-containing amino acids other than serine/threonine. The neighbouring amino acids and local structural features around the potential glycosylation site also play a significant role in determining the extent of glycosylation. All of these phenomena that yield glycosylation at the atypical sites are reported in a variety of biological systems, including different pathological conditions. Therefore, the discovery of more novel sequence patterns for N- and O-glycosylation may help in understanding the functions of complex biological processes and cellular functions. Taken together, all these information provided in this review would be helpful for the biological readers. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical efficacy of entecavir in treatment of hepatogenous diabetes

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GOU Wei

2013-06-01

Full Text Available ObjectiveTo observe the clinical efficacy of entecavir in the treatment of hepatogenous diabetes (HD. MethodsA retrospective analysis was performed on the clinical data of 72 HD patients, who were divided into treatment group (n=36 and control group (n=36. Both groups were given diabetic diet and received liver-protecting treatment, symptomatic treatment, and supportive treatment. In addition, the treatment group received oral entecavir (0.5 mg once daily. The therapeutic effect was assessed after 52 weeks of treatment; the serum hepatitis B virus (HBV DNA level, liver function (alanine aminotransferase, aspartate aminotransferase, total bilirubin, and albumin, blood glucose, and glycosylated hemoglobin were measured before and after treatment. The two groups were compared by t test (for measurement data and chi-square test (for numeration data. ResultsAfter 52 weeks of treatment, 29 (80.56% of the patients in treatment group had virological response, versus 7 (19.44% of those in control group (χ2 = 18.00, P＜0.01; 26 (72.22% of the patients in treatment group had liver function recovery and controlled diabetes, versus 16 (44.44% of those in control group (χ2=5.774, P＜0.05. The treatment group showed significant improvements in liver function and blood glucose after treatment (P＜0.05; the treatment group had significantly lower glycosylated hemoglobin and fasting blood glucose than the control group (P＜0.01. ConclusionIn the treatment of HBV DNA-positive hepatitis B cirrhosis with HD, entecavir not only can effectively inhibit the replication of viral DNA and promote the recovery of liver function, but also can effectively control HD.

The role of glycosylation in breast cancer metastasis and cancer control

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Alexandra eKölbl

2015-10-01

Full Text Available AbstractGlycosylation and its correlation to the formation of remote metastasis in breast cancer had been an important scientific topic in the last 25 years. With the development of new analytical techniques new insights were gained on the mechanisms underlying metastasis formation and the role of aberrant glycosylation within. Mucin-1 and Galectin were recognized as key players in glycosylation. Interestingly, aberrant carbohydrate structures seem to support the development of brain metastasis in breast cancer patients, as changes in glycosylation structures facilitate an overcoming of blood-brain barrier. Changes in the gene expression of glycosyltransferases are the leading cause for a modification of carbohydrate chains, so that also altered gene expression plays a role for glycosylation. In consequence, glycosylation and changes within can be useful for cancer diagnosis, determination of tumour stage and prognosis, but can as well be targets for therapeutic strategies. Thus, further research on this topic would worth wile for cancer combating.

Fish hemoglobins

OpenAIRE

Souza,P.C. de; Bonilla-Rodriguez,G.O.

2007-01-01

Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta) and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemica...

Glucose kinetics in infants of diabetic mothers

International Nuclear Information System (INIS)

Cowett, R.M.; Susa, J.B.; Giletti, B.; Oh, W.; Schwartz, R.

1983-01-01

Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-[U-13C] glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in the infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia

Glycosylated hemoglobin testing in the National Social Life, Health, and Aging Project.

Science.gov (United States)

Gregg, Forest T; O'Doherty, Katie; Schumm, L Philip; McClintock, Martha K; Huang, Elbert S

2014-11-01

Longitudinal biomeasures of health are still new in nationally representative social science survey research. Data measuring blood sugar control provide opportunities for understanding the development of diabetes and its complications in older adults, but researchers must be aware that some of the differences across time can be due to variations in measurement procedures. This is a well-recognized issue whenever all samples cannot be assayed at the same time and we sought to present the analytic methods to quantify and adjust for the variation. We collected and analyzed HbA1C, glycated hemoglobin, a biomeasure of average blood sugar concentrations within the past few months. Improvements were made in the collection protocol for Wave 2, and assays were performed by a different lab. The HbA1C data obtained during Wave 1 and Wave 2 are consistent with the expected population distributions for differences by gender, age, race/ethnicity, and diabetes status. Age-adjusted mean HbA1C declined slightly from Wave 1 to Wave 2 by -0.19 (95% confidence interval [CI]: -0.27, -0.10), and the average longitudinal change was -0.12 (95% CI: -0.18, -0.06). Collection of HbA1C in Wave 2 permits researchers to examine the relationship between HbA1C and new health and social measures added in Wave 2, and to identify factors related to the change in HbA1C. Changes in collection protocol and labs between waves may have yielded small systematic differences that require analysts to carefully interpret absolute HbA1C values. We recommend analytic methods for cross wave differences in HbA1C and steps to ensure cross wave comparability in future studies. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Point of care hematocrit and hemoglobin in cardiac surgery: a review.

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Myers, Gerard J; Browne, Joe

2007-05-01

The use of point-of-care blood gas analyzers in cardiac surgery has been on the increase over the past decade. The availability of these analyzers in the operating room and post-operative intensive care units eliminates the time delays to transport samples to the main laboratory and reduces the amount of blood sampled to measure such parameters as electrolytes, blood gases, lactates, glucose and hemoglobin/hematocrit. Point-of-care analyzers also lead to faster and more reliable clinical decisions while the patient is still on the heart lung machine. Point-of-care devices were designed to provide safe, appropriate and consistent care of those patients in need of rapid acid/base balance and electrolyte management in the clinical setting. As a result, clinicians rely on their values to make decisions regarding ventilation, acid/base management, transfusion and glucose management. Therefore, accuracy and reliability are an absolute must for these bedside analyzers in both the cardiac operating room and the post-op intensive care units. Clinicians have a choice of two types of technology to measure hemoglobin/hematocrit during bypass, which subsequently determines their patient's level of hemodilution, as well as their transfusion threshold. All modern point-of-care blood gas analyzers measure hematocrit using a technology called conductivity, while other similar devices measure hemoglobin using a technology called co-oximetry. The two methods are analyzed and compared in this review. The literature indicates that using conductivity to measure hematocrit during and after cardiac surgery could produce inaccurate results when hematocrits are less than 30%, and, therefore, result in unnecessary homologous red cell transfusions in some patients. These inaccuracies are influenced by several factors that are common and unique to cardiopulmonary bypass, and will also be reviewed here. It appears that the only accurate, consistent and reliable method to determine hemodilution

Effect of chicory seed extract on glucose tolerance test (GTT and metabolic profile in early and late stage diabetic rats

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Ghamarian Abdolreza

2012-10-01

Full Text Available Abstract Background and purpose of the study The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT and blood biochemical indices of experimentally-induced hyperglycemic rats. Methods Late stage and early stage of Type 2 diabetes mellitus (T2DM were induced in rats by streptozotocin (STZ and a combination of STZ and niacinamide (NIA/STZ, respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days. Body weight and fasting blood sugar (FBS were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c and sera for alanine aminotransferase (ALT, aspartate aminotransferase (AST, nitric oxide (NO, triacylglycerol (TG, total cholesterol (TC, total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days. Results During 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p Conclusions Chicory appeared to have short-term (about 2 hours, as far as GTT is concerned and long-term (28 days, in this study effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.

A multi-pronged investigation into the effect of glucose starvation and culture duration on fed-batch CHO cell culture

DEFF Research Database (Denmark)

Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian

2015-01-01

to the interplay between the dilution effect associated with change in specific productivity of mAbs and the changed nucleotide sugar metabolism. Herein, we also show and discuss that increased cell culture duration negatively affect the maturation of glycans. In addition, comparative proteomics analysis of cells......In this study, omics-based analysis tools were used to explore the effect of glucose starvation and culture duration on monoclonal antibody (mAb) production in fed-batch CHO cell culture to gain better insight into how these parameters can be controlled to ensure optimal mAb productivity...... and quality. Titer and N-glycosylation of mAbs, as well as proteomic signature and metabolic status of the production cells in the culture were assessed. We found that the impact of glucose starvation on the titer and N-glycosylation of mAbs was dependent on the degree of starvation during early stationary...

Hypoglycemic, hepatoprotective and molecular docking studies of 5-[(4-chlorophenoxy methyl]-1, 3, 4-oxadiazole-2-thiol

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Naureen Shehzadi

2018-05-01

Full Text Available The present study aimed at the evaluation of anti-hyperglycemic and hepatoprotective potential of a new drug candidate, 5-[(4-chlorophenoxy methyl]-1,3,4-oxadiazole-2-thiol (OXCPM through in vitro and in vivo assays, respectively. The compound displayed excellent dose-dependent ɑ-amylase (28.0-92.0%, ɑ-glucosidase (40.3-93.1% and hemoglobin glycosylation (9.0%-54.9% inhibitory effects and promoted the uptake of glucose by the yeast cells (0.2 to 26.3%. The treatment of the isoniazid- and rifampicin- (p.o., 50 mg/kg of each intoxicated rats with OXCPM (100 mg/kg, p.o. resulted in restoring the normal serum levels of the non-enzymatic (total bilirubin, total protein and albumin and bringing about a remarkable decrease in the levels of enzymatic (alanine transaminases, aspartate transaminases and alkaline phosphatase biomarkers. The molecular docking studies indicated high binding affinity of the compound for hyperglycemia-related protein targets; fructose-1,6-bisphosphatase, beta2-adrenergic receptors and glucokinase. The results indicate that OXCPM may not only reduce hyperglycemia by enzyme inhibition but also the disease complications through protection of hemoglobin glycosylation and hepatic injury.

Brewer's Yeast Improves Glycemic Indices in Type 2 Diabetes Mellitus.

Science.gov (United States)

Hosseinzadeh, Payam; Javanbakht, Mohammad Hassan; Mostafavi, Seyed-Ali; Djalali, Mahmoud; Derakhshanian, Hoda; Hajianfar, Hossein; Bahonar, Ahmad; Djazayery, Abolghassem

2013-10-01

Brewer's yeast may have beneficial effects on insulin receptors because of itsglucose tolerance factor in diabetic patients. This study was conducted to investigate the effects of brewer's yeast supplementation on glycemic indices in patients with type 2 diabetes mellitus. In a randomized double-blind controlled clinical trial, 84 adults (21 men and 63 women) aged 46.3 ± 6.1 years old with type 2 diabetes mellitus were recruited and divided randomly into two groups: Supplement group receiving brewer's yeast (six 300mg tablets/day, total 1800 mg) and control group receiving placebo (six 300mg tablets/day) for 12 weeks. Body weight, height, body mass index, food consumption (based on 24h food record), fasting blood sugar (FBS), glycosylated hemoglobin, insulin sensitivity, and insulin resistance were measured before and after the intervention. Data analysis was performed using the Statistical Package for Social Sciences (version 18.0). The changes in FBS, glycosylated hemoglobin, and insulin sensitivity were significantly different between the two groups during the study (respectively P brewer›s yeast besides the usual treatment of diabetes can ameliorate blood glucose variables in type 2 diabetes mellitus.

Hemoglobin C, S-C, and E Diseases

Science.gov (United States)

... quickly than others, resulting in chronic anemia. Hemoglobin C disease Hemoglobin C disease occurs mostly in blacks. ... a common complication of hemoglobin C disease. Hemoglobin S-C disease Hemoglobin S-C disease occurs in people who ...

Selection of aptamers specific for glycated hemoglobin and total hemoglobin using on-chip SELEX.

Science.gov (United States)

Lin, Hsin-I; Wu, Ching-Chu; Yang, Ching-Hsuan; Chang, Ko-Wei; Lee, Gwo-Bin; Shiesh, Shu-Chu

2015-01-21

Blood glycated hemoglobin (HbA1c) levels reflecting average glucose concentrations over the past three months are fundamental for the diagnosis, monitoring, and risk assessment of diabetes. It has been hypothesized that aptamers, which are single-stranded DNAs or RNAs that demonstrate high affinity to a large variety of molecules ranging from small drugs, metabolites, or proteins, could be used for the measurement of HbA1c. Aptamers are selected through an in vitro process called systematic evolution of ligands by exponential enrichment (SELEX), and they can be chemically synthesized with high reproducibility at relatively low costs. This study therefore aimed to select HbA1c- and hemoglobin (Hb)-specific single-stranded DNA aptamers using an on-chip SELEX protocol. A microfluidic SELEX chip was developed to continuously and automatically carry out multiple rounds of SELEX to screen specific aptamers for HbA1c and Hb. HbA1c and Hb were first coated onto magnetic beads. Following several rounds of selection and enrichment with a randomized 40-mer DNA library, specific oligonucleotides were selected. The binding specificity and affinity were assessed by competitive and binding assays. Using the developed microfluidic system, the incubation and partitioning times were greatly decreased, and the entire process was shortened dramatically. Both HbA1c- and Hb-specific aptamers selected by the microfluidic system showed high specificity and affinity (dissociation constant, Kd = 7.6 ± 3.0 nM and 7.3 ± 2.2 nM for HbA1c and Hb, respectively). With further refinements in the assay, these aptamers may replace the conventional antibodies for in vitro diagnostics applications in the near future.

Surface glycosylation profiles of urine extracellular vesicles.

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Jared Q Gerlach

Full Text Available Urinary extracellular vesicles (uEVs are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications.

Hemoglobin H disease in the Al-Qatif region of Saudi Arabia

International Nuclear Information System (INIS)

Ankra-Badu, George A.; Al-Jama, A.; Al-Kadim, Y.

2001-01-01

The Al-Qatif region in the Eastern Province of Saudi Arabia has thehighest prevalence of alpha-thalassemia genes in the Kingdom. Hemoglobin H(Hb H) disease, however, has been rarely reported. We decided therefore toverify the rarity of disease and characterize the presenting features incases identified. All patients seen in Qatif Central Hospital betweenSeptember 1988 and November 1990 with low red cell indices were screened forHb H disease and those found positive had clinical data compiled from theirhospital records and analyzed. Thirty-nine cases of Hb H were diagnosed. Themean age of patients was 18 years. The mean hemoglobin was 13.5 g/dL forneonates and 7.6 g/dL for others. The mean Hb Bart's level was 27.5% inneonates and the mean Hb H level in others was 11.1%. In addition to low redcell indices, all patients had a high red cell distribution width (RDW) meanof 25.6%. The main clinical signs were jaundice and hepatosplenomegaly.Concurrent glucose-6-phosphate Dehydrogenase (G6PD) deficiency was seen in28.2% of patients. Hemoglobin H disease is not uncommon in the Al-Qatifregion of Saudi Arabia. The red cell indices may mimic iron deficiency, whichshould be excluded by the presence of jaundice and organomegaly. Thecondition often co-exists with G6PD deficiency. (author)

Positive Association of Vitamin E Supplementation with Hemoglobin Levels in Mildly Anemic Healthy Pakistani Adults.

Science.gov (United States)

Jilani, Tanveer; Azam, Iqbal; Moiz, Bushra; Mehboobali, Naseema; Perwaiz Iqbal, Mohammad

2015-01-01

Hemoglobin levels slightly below the lower limit of normal are common in adults in the general population in developing countries. A few human studies have suggested the use of antioxidant vitamins in the correction of mild anemia. The objective of the present study was to investigate the association of vitamin E supplementation in mildly anemic healthy adults with post-supplemental blood hemoglobin levels in the general population of Karachi, Pakistan. In a single-blinded and placebo-controlled randomized trial, 124 mildly anemic subjects from the General Practitioners' Clinics and personnel of the Aga Khan University were randomized into intervention (n = 82) and control (n = 42) group. In the intervention group, each subject was given vitamin E (400 mg) everyday for a period of three months, while control group subjects received a placebo. Eighty six subjects completed the trial. Fasting venous blood was collected at baseline and after three months of supplementation. Hemoglobin levels and serum/plasma concentrations of vitamin E, vitamin B12, folate, ferritin, serum transferrin receptor (sTfR), glucose, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, creatinine, total-antioxidant-status and erythropoietin were measured and analyzed using repeated measures ANOVA and multiple linear regression. The adjusted regression coefficients (β) and standard error [SE(β)] of the significant predictors of post-supplemental hemoglobin levels were serum concentration of vitamin E (0.983[0.095]), gender (- 0.656[0.244]), sTfR (- 0.06[0.02]) and baseline hemoglobin levels (0.768[0.077]). The study showed a positive association between vitamin E supplementation and enhanced hemoglobin levels in mildly anemic adults.

Method Development in the Regioselective Glycosylation of Unprotected Carbohydrates

DEFF Research Database (Denmark)

Niedbal, Dominika Alina

and the glycosylations were promoted by tetrabutylammonium bromide. The couplings were completely selective and gave rise to a number of 1,6-linked disaccharides with 1,2- cis-linked orientation. Project 2: Boron-mediated glycosylation of unprotected carbohydrates Boron-mediated regioselective Koenigs...

The Effects of 6 Isocaloric Meals Pattern on Blood Lipid Profile, Glucose, Hemoglobin A1c, Insulin and Malondialdehyde in Type 2 Diabetic Patients: A Randomized Clinical Trial

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Moosa Salehi

2014-09-01

Full Text Available Background: The present clinical trial study aims at investigating the effect of daily energy intake in 6 isocaloric meals in comparison with the current meal pattern (3 meals and 2 small snacks per day on type 2 diabetes risk markers in diabetes during 3-month period. Methods: Eighty four type 2 diabetes patients were randomly divided into 6 isocaloric meal diet or a balanced diet (3 meals and 2 snacks previous meal pattern. The planned reduced calorie diets for both groups were identical except for the meal pattern. Blood samples were analyzed before and after the investigation for fasting blood sugar (FBS, two-hour post-prandial glucose (2hPP, insulin, hemoglobin A1c (HbA1c, total cholesterol, triglyceride, HDL-C, LDL-C, and molondialdehyde (MDA concentrations. Results: HbA1c (P=0.00 and body mass index (BMI (P=0.04 values decreased significantly in the 6 isocaloric meal pattern compared with the controls. There were no significant differences in fasting serum glucose (P=0.09, insulin (P=0.65, total cholesterol (P=0.32, LDL-C (P=0.43, HDL-C (P=0.40 cholesterol, triglyceride (P=0.40, MDA (P=0.13 and 2hPP serum glucose (P=0.30 concentrations between the 6 isocaloric meal and tradition meal pattern. Conclusion: Six isocaloric meal pattern in comparison with the current meal pattern led to weight loss and improved glycemic control. Serum lipid profile and MDA did not change significantly. Trial Registration Number: IRCT201205179780N1

Distribution of N-glycosylation sequons in proteins: how apart are they?

DEFF Research Database (Denmark)

Rao, Shyama Prasad; Buus, Ole Thomsen; Wollenweber, Bernd

2011-01-01

of experimentally confirmed eukaryotic N-glycoproteins we analyzed the relative position and distribution of sequons. N-Glycosylation probability was found to be lower in the termini of protein sequences compared to the mid region. N-glycosylated sequons were found much farther from C terminus compared to the N......N-glycosylation is a common protein modification process, which affects a number of properties of proteins. Little is known about the distribution of N-glycosylation sequons, for example, the distance between glycosylated sites and their position in the protein primary sequence. Using a large set......-terminus of the protein sequence and this effect was more pronounced for NXS sequons. The distribution of sequons, modeled based on balls-in-boxes classical occupancy, showed a near-maximum probability. Considerable proportion of sequons was found within a distance of ten amino acids, indicating that the steric hindrance...

Effect of skim milk and dahi (yogurt) on blood glucose, insulin, and lipid profile in rats fed with high fructose diet.

Science.gov (United States)

Yadav, Hariom; Jain, Shalini; Sinha, P R

2006-01-01

In the present study, the effect of skim milk and the fermented milk product named dahi (yogurt) on plasma glucose, insulin, and lipid levels as well as on liver glycogen and lipid contents in rats fed with high fructose diet has been investigated. Rats were fed with high fructose diet (21%) supplemented with skim milk, dahi (10 g/day each), or no milk product (control group) for 6 weeks. After 6 weeks of high fructose diet administration, the plasma glucose became significantly higher in control animals (246 mg/dL), whereas it was lower in skim milk (178 mg/dL)- and dahi (143 mg/dL)-fed rats. The glucose tolerance became impaired at the third week of feeding of high fructose diet in control animals, whereas in skim milk- and dahi-fed animals achievement of glucose intolerance was delayed until the fourth and fifth week, respectively. Blood glycosylated hemoglobin and plasma insulin were significantly lower in skim milk (10% and 34%, respectively)- and dahi (17%, and 48%, respectively)-fed animals than those of the control group. Plasma total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and very-low-density lipoprotein-cholesterol and blood free fatty acids were significantly lower in skim milk (13%, 14%, 14%, 19%, and 14%, respectively)- and dahi (22%, 33%, 30%, 33%, and 29%, respectively)-fed animals as compared with control animals. Moreover, the total cholesterol, triglyceride, and glycogen contents in liver tissues were also lower in skim milk (55%, 50%, and 36%, respectively)- and dahi (64%, 27%, and 4%, respectively)-fed animals as compared with control animals. In contrast, high-density lipoprotein-cholesterol in plasma was higher in skim milk (14%)- and dahi (29%)-fed animals as compared with control animals. These results indicate that skim milk and its fermented milk product, dahi, delay the progression of fructose-induced diabetes and dyslipidemia in rats and that these may be useful as antidiabetic food supplements that can be

Interaction of thyroid hormone and hemoglobin: nature of the interaction and effect of hemoglobin on thyroid hormone radioimmunoassay

International Nuclear Information System (INIS)

Davis, P.J.; Yoshida, K.; Schoenl, M.

1980-01-01

Gel filtration of human erythrocyte (RBC) lysate incubated with labeled thyroxine (Tu) or triiodothyronine (Tt) revealed co-elution of a major iodothyronine-binding fraction (R-2) and hemoglobin. Solutions of purified human hemoglobin and Tt also showed co-elution of hormone and hemoglobin. Because hematin and protoporphyrin were shown to bind labeled Tt, the oxygen-binding site on hemoglobin was excluded as the site of iodothyronine-hemoglobin interaction. Analysis of hormone binding by heme and globin moieties showed Tt binding to be limited to the heme fraction. Addition of excess unlabeled Tt to hemoglobin or heme incubated with labeled Tt indicated 75% to 90% of hormone binding was poorly dissociable. These observations suggested that the presence of hemoglobin in RBC lysate or in serum could influence the measurement of Tu and Tt by specific radioimmunoassay (RIA). Subsequent studies of the addition to serum of human hemoglobin revealed a significant reduction in Tt and Tu detectable by RIA in the presence of this protein. The effect was influenced by the concentration of hemoglobin and by duration and temperature of incubations of hemoglobin and serum prior to RIA

Evaluation of insulin resistance in two kinds of South American camelids: llamas and alpacas.

Science.gov (United States)

Araya, A V; Atwater, I; Navia, M A; Jeffs, S

2000-10-01

Insulin resistance was evaluated in South American camelids, llamas and alpacas, by use of the minimal model test and the insulin tolerance test. Animals were catheterized for long-term studies and tamed to minimize stress during evaluation. Results indicated a low insulin sensitivity index (SI) = 0 to 0.97, median = 0.39 x 10(-4) min/uIU x ml, about a fifth the value in other mammals and humans. The KITT was between 1.43 and 3.19 %/min, also significantly lower than that reported for humans. Glycosylated hemoglobin concentration was 6%, and HbAlc concentration was 5.5%; red blood cell lifetime, as measured by use of the 51Cr method, was 120 days, similar to the value in humans. We concluded that llamas and alpacas have naturally higher blood glucose concentration than do humans and other mammals during the glucose tolerance test. Using the same mathematical tools to evaluate glucose metabolism as those used in people, South American camelids appear to be resistant to insulin. Thus, the South American camelid may be a useful new animal model for the study of sugar metabolism and various facets of diabetes mellitus, especially protection from the deleterious effects of glycosylation.

Glycemic changes after vitamin D supplementation in patients with type 1 diabetes mellitus and vitamin D deficiency

International Nuclear Information System (INIS)

Khalid S Aljabri; Somoa A Bokhari; Murtadha J. Khan

2010-01-01

A prospective, nonblinded and nonrandomized controlled trial was conducted to test the hypothesis that vitamin D supplementation would improve glycemic control in patients with type 1 diabetes mellitus who have vitamin D deficiency. Patients and 0 Eighty patients with type 1 diabetes mellitus who had 25-hydroxyvitamin D levels less than 50 nmol/L were assigned to receive 4000 IU of vitamin D3. Calcium supplements were provided to ensure a total calcium intake of 1200 mg/d. Glycosylated hemoglobin and 25-hydroxyvitamin D levels were measured at baseline and at 12 weeks.There was a significant difference in mean (SD) glycosylated hemoglobin level (%) between the groups that achieved 25-hydroxyvitamin D levels of 51 nmol/L at 12 weeks (P=.02). There was a significant difference in glycosylated hemoglobin change from baseline between the groups that achieved 25-hydroxyvitamin D levels of 51 nmol/L at 12 weeks (P=.04). There was a significant difference in 25-hydroxyvitamin D level between the groups that achieved glycosylated hemoglobin levels of 9.9 at 12 weeks (P=.001). Patients were more likely to achieve lower glycosylated hemoglobin levels at 12 weeks if they had higher 25-hydroxyvitamin D levels at 12 weeks (r=-0.4, P=.001).There was an observed effect of vitamin D supplementation on glycemic control in vitamin D-replete, type 1 diabetes mellitus patients. Further studies are needed to determine if these findings are applicable (Author).

The effectiveness of stress management training on blood glucose control in patients with type 2 diabetes.

Science.gov (United States)

Zamani-Alavijeh, Fereshteh; Araban, Marzieh; Koohestani, Hamid Reza; Karimy, Mahmood

2018-01-01

Type 2 diabetes is a chronic disease that is expanding at an alarming rate in the world. Research on individuals with type 2 diabetes showed that stressful life events cause problems in the effective management and control of diabetes. This study aimed at investigating the effect of a stress management intervention on blood glucose control in individuals with type 2 diabetes referred to Zarandeh clinic, Iran. In this experimental study, 230 individuals with type 2 diabetes (179 female and 51 male) were enrolled and assigned to experimental (n = 115) and control (n = 115) groups. A valid and reliable multi-part questionnaire including demographics, Perceived Stress Scale, Coping Inventory for Stressful Situations, Coping Self-Efficacy Scale, and multidimensional scale of perceived social support was used to for data collection. The experimental group received a training program, developed based on the social cognitive theory and with an emphasis on improving self-efficacy and perceived social support, during eight sessions of one and a half hours. Control group received only standard care. Data were analyzed using SPSS 15 applying the t test, paired t-tests, Pearson correlation coefficient, and Chi square analysis. The significance level was considered at 0.05. Before the intervention, the mean perceived stress scores of the experimental and control groups were 33.9 ± 4.6 and 35 ± 6.5, respectively, and no significant difference was observed (p > 0.05). However, after the intervention, the mean perceived stress score of the experimental group (26.7 ± 4.7) was significantly less than that of the control group (34.5 ± 7) (p = 0.001). Before the intervention, the mean scores of HbA1c in the experimental and control groups were 8.52 ± 1 and 8.42 ± 1.2, respectively, and there was no significant difference between the two groups. However, after the intervention, the results showed a significant decrease in glycosylated

Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

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Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

2011-01-01

Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

International Nuclear Information System (INIS)

Watanabe, Ayahisa; Nishijima, Ken-ichi; Zhao, Songji; Tamaki, Nagara; Kuge, Yuji; Tanaka, Yoshikazu; Itoh, Takeshi; Takemoto, Hiroshi

2012-01-01

Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes. Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of 123 I-GLP-1 or 123 I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using 125 I-GLP-1 or 125 I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured. In the noninvasive imaging studies, a relatively high accumulation level of 123 I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of 123 I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of 123 I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using 125 I-labeled peptides. The AUC of 125 I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1. This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals. (author)

Adverse effects during the oral glucose tolerance test in post-bariatric surgery patients

OpenAIRE

Andrade,Heliana Fernanda de Albuquerque; Pedrosa,William; Diniz,Maria de Fátima Haueisen Sander; Passos,Valéria Maria Azeredo

2016-01-01

ABSTRACT Objective The oral glucose tolerance test (OGTT) is used in the screening of gestational diabetes, in diagnosis of type 2 diabetes in conjunction with fasting blood glucose and glycated hemoglobin. The aim of this study was to examine the incidence and risk factors of adverse effects of OGTT in patients who underwent bariatric surgery, in addition to proposing standardization for ordering the OGTT in these patients. Subjects and methods This study assessed the incidence of adverse ...

Hemoglobin Test: MedlinePlus Lab Test Information

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... page: https://medlineplus.gov/labtests/hemoglobintest.html Hemoglobin Test To use the sharing features on this page, please enable JavaScript. What is a Hemoglobin Test? A hemoglobin test measures the levels of hemoglobin ...

Comparable Dietary Patterns Describe Dietary Behavior across Ethnic Groups in the Netherlands, but Different Elements in the Diet Are Associated with Glycated Hemoglobin and Fasting Glucose Concentrations.

Science.gov (United States)

Dekker, Louise H; van Dam, Rob M; Snijder, Marieke B; Peters, Ron J G; Dekker, Jacqueline M; de Vries, Jeanne H M; de Boer, Evelien J; Schulze, Matthias B; Stronks, Karien; Nicolaou, Mary

2015-08-01

Ethnic minority populations in Western societies suffer from a disproportionate burden of type 2 diabetes (T2D). Insight into the role of dietary patterns in T2D may assist public health nutrition efforts in addressing these health disparities. We explored the association between dietary patterns and biomarkers of T2D in 5 ethnic groups living in Amsterdam, Netherlands. A total of 3776 men and women aged 18-70 y of Dutch, South Asian Surinamese, African-Surinamese, Turkish, and Moroccan origin from the HELIUS (HEalthy LIfe in an Urban Setting) study were included. Diet was assessed by using a food-frequency questionnaire, and dietary patterns were derived separately per ethnic group. First, food group-based dietary patterns were derived by using principal components analysis and the association with glycated hemoglobin (HbA1c) and plasma fasting glucose was assessed by using multivariable linear regression. Second, biomarker-driven dietary patterns based on HbA1c and fasting glucose concentrations were derived by applying reduced rank regression. Two comparable food group-based dietary patterns were identified in each ethnic group: a "meat and snack" pattern and a "vegetable" pattern. The meat-and-snack pattern derived within the Dutch origin population was significantly associated with HbA1c (β = 0.09; 95% CI: 0.00, 0.19) and fasting glucose (β = 0.18; 95% CI: 0.09, 0.26) concentrations. A biomarker-derived pattern characterized by red and processed meat was observed among Dutch-origin participants; however, among ethnic minority groups, this pattern was characterized by other foods including ethnicity-specific foods (e.g., roti, couscous). Although similar food group dietary patterns were derived within 5 ethnic groups, the association of the meat-and-snack pattern with fasting glucose concentrations differed by ethnicity. Taken together with the finding of ethnic differences in biomarker-driven dietary patterns, our results imply that addressing T2D risk in

Clinical Implications of Glucose Variability: Chronic Complications of Diabetes

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Hye Seung Jung

2015-06-01

Full Text Available Glucose variability has been identified as a potential risk factor for diabetic complications; oxidative stress is widely regarded as the mechanism by which glycemic variability induces diabetic complications. However, there remains no generally accepted gold standard for assessing glucose variability. Representative indices for measuring intraday variability include calculation of the standard deviation along with the mean amplitude of glycemic excursions (MAGE. MAGE is used to measure major intraday excursions and is easily measured using continuous glucose monitoring systems. Despite a lack of randomized controlled trials, recent clinical data suggest that long-term glycemic variability, as determined by variability in hemoglobin A1c, may contribute to the development of microvascular complications. Intraday glycemic variability is also suggested to accelerate coronary artery disease in high-risk patients.

Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.

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Koga, Masafumi; Inada, Shinya; Shimizu, Sayoko; Hatazaki, Masahiro; Umayahara, Yutaka; Nishihara, Eijun

2015-01-01

Hb Himeji (β140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, Preaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in β chain of hemoglobin is suggested to be involved in aldimine formation reaction. © 2015 by the Association of Clinical Scientists, Inc.

Twenty-four-hour variations in blood glucose level in Japanese type 2 diabetes patients based on continuous glucose monitoring.

Science.gov (United States)

Hajime, Maiko; Okada, Yosuke; Mori, Hiroko; Otsuka, Takashi; Kawaguchi, Mayuko; Miyazaki, Megumi; Kuno, Fumi; Sugai, Kei; Sonoda, Satomi; Tanaka, Kenichi; Kurozumi, Akira; Narisawa, Manabu; Torimoto, Keiichi; Arao, Tadashi; Tanaka, Yoshiya

2018-01-01

High fluctuations in blood glucose are associated with various complications. The correlation between glycated hemoglobin (HbA1c) level and fluctuations in blood glucose level has not been studied in Japanese patients with type 2 diabetes. In the present study, blood glucose profile stratified by HbA1c level was evaluated by continuous glucose monitoring (CGM) in Japanese type 2 diabetes patients. Our retrospective study included 294 patients with type 2 diabetes who were divided by HbA1c level into five groups (≥6.0 to level and CGM data was analyzed. The primary end-point was the difference in blood glucose fluctuations among the HbA1c groups. The mean blood glucose level increased significantly with increasing HbA1c (P trend  levels of maximum blood glucose, minimum blood glucose, each preprandial blood glucose, each postprandial maximum blood glucose, range of increase in postprandial glucose from pre-meal to after breakfast, the area under the blood concentration-time curve >180 mg/dL and percentage of the area under the blood concentration-time curve >180 mg/dL were higher with higher HbA1c. Mean glucose level and pre-breakfast blood glucose level were significant and independent determinants of HbA1c. In Japanese patients treated for type 2 diabetes, the mean amplitude of glycemic excursions did not correlate with HbA1c, making it difficult to assess blood glucose fluctuations using HbA1c. Parameters other than HbA1c are required to evaluate fluctuations in blood glucose level in patients receiving treatment for type 2 diabetes. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

New diagnostic criteria for diabetes: is the change from glucose to HbA1c possible in all populations?

DEFF Research Database (Denmark)

Jørgensen, Marit Eika; Bjerregaard, Peter; Borch-Johnsen, Knut

2010-01-01

Recently, a change of the diagnostic tool for diabetes from an oral glucose tolerance test (OGTT) to hemoglobin A1c (HbA1c) has been suggested. The aim of the study was to assess whether ethnicity modified the association between glucose levels and HbA1c and to compare diabetes prevalence accordi...

New diagnostic criteria for diabetes: is the change from glucose to HbA1c possible in all populations?

DEFF Research Database (Denmark)

Jørgensen, Marit Eika; Bjerregaard, Peter; Borch-Johnsen, Knut

2010-01-01

Recently, a change of the diagnostic tool for diabetes from an oral glucose tolerance test (OGTT) to hemoglobin A1c (HbA1c) has been suggested. The aim of the study was to assess whether ethnicity modified the association between glucose levels and HbA1c and to compare diabetes prevalence according...

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

Science.gov (United States)

Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie; Delanghe, Joris

2015-01-01

Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N=66) and prostatitis patients (N=36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (Pprostatitis patients from HV (Pprostatitis patients compared to HV (Pprostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

A new hemoglobin gene from soybean: a role for hemoglobin in all plants

DEFF Research Database (Denmark)

Anderson, C R; Jensen, E O; LLewellyn, D J

1996-01-01

We have isolated a new hemoglobin gene from soybean. It is expressed in cotyledons, stems of seedlings, roots, young leaves, and in some cells in the nodules that are associated with the nitrogen-fixing Bradyrhizobium symbiont. This contrasts with the expression of the leghemoglobins, which...... are active only in the infected cells of the nodules. The deduced protein sequence of the new gene shows only 58% similarity to one of the soybean leghemoglobins, but 85-87% similarity to hemoglobins from the nonlegumes Parasponia, Casuarina, and barley. The pattern of expression and the gene sequence...... indicate that this new gene is a nonsymbiotic legume hemoglobin. The finding of this gene in legumes and similar genes in other species strengthens our previous suggestion that genomes of all plants contain hemoglobin genes. The specialized leghemoglobin gene family may have arisen from a preexisting...

The Emerging Importance of IgG Fab Glycosylation in Immunity.

Science.gov (United States)

van de Bovenkamp, Fleur S; Hafkenscheid, Lise; Rispens, Theo; Rombouts, Yoann

2016-02-15

Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ∼15-25% of serum IgG contains glycans within the variable domains. These so-called "Fab glycans" are primarily highly processed complex-type biantennary N-glycans linked to N-glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity. Copyright © 2016 by The American Association of Immunologists, Inc.

Non-invasive hemoglobin monitoring.

Science.gov (United States)

Joseph, Bellal; Haider, Ansab; Rhee, Peter

2016-09-01

Technology has transformed the practice of medicine and surgery in particular over the last several decades. This change in practice has allowed diagnostic and therapeutic tests to be performed less invasively. Hemoglobin monitoring remains one of the most commonly performed diagnostic tests in the United States. Recently, non-invasive hemoglobin monitoring technology has gained popularity. The aim of this article is to review the principles of how this technology works, pros and cons, and the implications of non-invasive hemoglobin technology particularly in trauma surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Deciphering a pathway of Halobacterium salinarum N-glycosylation

Science.gov (United States)

Kandiba, Lina; Eichler, Jerry

2015-01-01

Genomic analysis points to N-glycosylation as being a common posttranslational modification in Archaea. To date, however, pathways of archaeal N-glycosylation have only been described for few species. With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. As in Hfx. volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). Introduction of these Hbt. salinarum genes into Hfx. volcanii mutant strains deleted of the homologous sequence restored the lost activity. Moreover, transcription of the Hbt. salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. Based on the results obtained in this study, the first description of an N-glycosylation pathway in Hbt. salinarum is offered. PMID:25461760

Role of sodium glucose cotransporter-2 inhibitors in type I diabetes mellitus

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Ahmadieh H

2017-05-01

Full Text Available Hala Ahmadieh,1 Nisrine Ghazal,2 Sami T Azar3 1Faculty of Medicine, Clinical Sciences Department, Beirut Arab University, 2Department of Endocrinology and Metabolism, American University of Beirut, Beirut, Lebanon; 3Department of Internal Medicine, Division of Endocrinology, American University of Beirut, New York, NY, USA Abstract: The burden of diabetes mellitus (DM in general has been extensively increasing over the past few years. Selective sodium glucose cotransporter-2 (SGLT2 inhibitors were extensively studied in type 2 DM and found to have sustained urinary glucose loss, improvement of glycemic control, in addition to their proven metabolic effects on weight, blood pressure, and cardiovascular benefits. Type 1 DM (T1D patients clearly depend on insulin therapy, which till today fails to achieve the optimal glycemic control and metabolic targets that are needed to prevent risk of complications. New therapies are obviously needed as an adjunct to insulin therapy in order to try to achieve optimal control in T1D. Many oral diabetic medications have been tried in T1D patients as an adjunct to insulin treatment and have shown conflicting results. Adjunctive use of SGLT2 inhibitors in addition to insulin therapies in T1D was found to have the potential to improve glycemic control along with decrease in the insulin doses, as has been shown in certain animal and short-term human studies. Furthermore, larger well-randomized studies are needed to better evaluate their efficacy and safety in patients with T1D. Euglycemic diabetic ketoacidosis incidences were found to be increased among users of SGLT2 inhibitors, although the incidence remains very low. Recent beneficial effects of ketone body production and this shift in fuel energetics have been suggested based on the findings of protective cardiovascular benefits associated with one of the SGLT2 inhibitors. Keywords: glycemic control, glycosylated hemoglobin, euglucemic diabetic ketoacidosis

Blood Test: Hemoglobin A1C

Science.gov (United States)

... Why Are Hemoglobin A1c Tests Done? When a child has diabetes, hemoglobin A1c levels are followed to see how well medicines are working. If a child with diabetes has a high hemoglobin A1c level, it may ...

Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting

Directory of Open Access Journals (Sweden)

Idriss Ali

2011-04-01

Full Text Available Abstract Background In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. Method EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin. Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC was used to determine the within subject variability of measured hemoglobin. Results Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p Conclusion Hemoglobin determined by the HemoCue method is comparable to that determined by the other methods. The HemoCue photometer is therefore recommended for use as on-the-spot device for determining hemoglobin in resource poor setting.

Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

International Nuclear Information System (INIS)

Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh; O’Leary, Claire; Joshi, Lokesh; McMahon, Siobhán S.

2012-01-01

Highlights: ► Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. ► Neuronal glycosylation in injury and after ChABC treatment is unknown. ► In silico mining verified that glyco-related genes were differentially regulated after SCI. ► In vitro model system revealed abnormal sialylation in an injured environment. ► The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually α-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment with ChABC was successful in returning neuronal glycosylation to normal conditions at all timepoints for MAA, PNA and SNA-I staining

Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

Energy Technology Data Exchange (ETDEWEB)

Kilcoyne, Michelle; Sharma, Shashank [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McDevitt, Niamh; O' Leary, Claire [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland); Joshi, Lokesh [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McMahon, Siobhan S., E-mail: siobhan.mcmahon@nuigalway.ie [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland)

2012-04-13

Highlights: Black-Right-Pointing-Pointer Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. Black-Right-Pointing-Pointer Neuronal glycosylation in injury and after ChABC treatment is unknown. Black-Right-Pointing-Pointer In silico mining verified that glyco-related genes were differentially regulated after SCI. Black-Right-Pointing-Pointer In vitro model system revealed abnormal sialylation in an injured environment. Black-Right-Pointing-Pointer The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually {alpha}-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment

DISAL glycosyl donors for the synthesis of a linear hexasaccharide under mild conditions

DEFF Research Database (Denmark)

Petersen, Lars; Laursen, Jane B.; Larsen, K.

2003-01-01

The new class of glycosyl donors with a methyl 3,5-dinitrosalicylate (DISAL) anomeric leaving group has proved efficient for glycosylation under strictly neutral, mildly basic, or mildly acidic conditions. Here, we report the synthesis of novel DISAL disaccharide glycosyl donors prepared by easy...... nucleophilic aromatic substitution. These DISAL donors proved efficient in the synthesis of a starch-related hexasaccharide under very mild conditions. Glycosylations proceeded with alpha-selectivity and were compatible with Trt protecting groups....

1H-MRS Measured Ectopic Fat in Liver and Muscle in Danish Lean and Obese Children and Adolescents.

Science.gov (United States)

Fonvig, Cilius Esmann; Chabanova, Elizaveta; Andersson, Ehm Astrid; Ohrt, Johanne Dam; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

2015-01-01

This cross sectional study aims to investigate the associations between ectopic lipid accumulation in liver and skeletal muscle and biochemical measures, estimates of insulin resistance, anthropometry, and blood pressure in lean and overweight/obese children. Fasting plasma glucose, serum lipids, serum insulin, and expressions of insulin resistance, anthropometry, blood pressure, and magnetic resonance spectroscopy of liver and muscle fat were obtained in 327 Danish children and adolescents aged 8-18 years. In 287 overweight/obese children, the prevalences of hepatic and muscular steatosis were 31% and 68%, respectively, whereas the prevalences in 40 lean children were 3% and 10%, respectively. A multiple regression analysis adjusted for age, sex, body mass index z-score (BMI SDS), and pubertal development showed that the OR of exhibiting dyslipidemia was 4.2 (95%CI: [1.8; 10.2], p = 0.0009) when hepatic steatosis was present. Comparing the simultaneous presence of hepatic and muscular steatosis with no presence of steatosis, the OR of exhibiting dyslipidemia was 5.8 (95%CI: [2.0; 18.6], p = 0.002). No significant associations between muscle fat and dyslipidemia, impaired fasting glucose, or blood pressure were observed. Liver and muscle fat, adjusted for age, sex, BMI SDS, and pubertal development, associated to BMI SDS and glycosylated hemoglobin, while only liver fat associated to visceral and subcutaneous adipose tissue and intramyocellular lipid associated inversely to high density lipoprotein cholesterol. Hepatic steatosis is associated with dyslipidemia and liver and muscle fat depositions are linked to obesity-related metabolic dysfunctions, especially glycosylated hemoglobin, in children and adolescents, which suggest an increased cardiovascular disease risk.

Flagellar glycosylation in Clostridium botulinum.

Science.gov (United States)

Twine, Susan M; Paul, Catherine J; Vinogradov, Evgeny; McNally, David J; Brisson, Jean-Robert; Mullen, James A; McMullin, David R; Jarrell, Harold C; Austin, John W; Kelly, John F; Logan, Susan M

2008-09-01

Flagellins from Clostridium botulinum were shown to be post-translationally modified with novel glycan moieties by top-down MS analysis of purified flagellin protein from strains of various toxin serotypes. Detailed analyses of flagellin from two strains of C. botulinum demonstrated that the protein is modified by a novel glycan moiety of mass 417 Da in O-linkage. Bioinformatic analysis of available C. botulinum genomes identified a flagellar glycosylation island containing homologs of genes recently identified in Campylobacter coli that have been shown to be responsible for the biosynthesis of legionaminic acid derivatives. Structural characterization of the carbohydrate moiety was completed utilizing both MS and NMR spectroscopy, and it was shown to be a novel legionaminic acid derivative, 7-acetamido-5-(N-methyl-glutam-4-yl)-amino-3,5,7,9-tetradeoxy-D-glycero-alpha-D-galacto-nonulosonic acid, (alphaLeg5GluNMe7Ac). Electron transfer dissociation MS with and without collision-activated dissociation was utilized to map seven sites of O-linked glycosylation, eliminating the need for chemical derivatization of tryptic peptides prior to analysis. Marker ions for novel glycans, as well as a unique C-terminal flagellin peptide marker ion, were identified in a top-down analysis of the intact protein. These ions have the potential for use in for rapid detection and discrimination of C. botulinum cells, indicating botulinum neurotoxin contamination. This is the first report of glycosylation of Gram-positive flagellar proteins by the 'sialic acid-like' nonulosonate sugar, legionaminic acid.

Increased glucose dependence in resting, iron-deficient rats

International Nuclear Information System (INIS)

Brooks, G.A.; Henderson, S.A.; Dallman, P.R.

1987-01-01

Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 ± 0.2 compared with 13.8 ± 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6- 3 H]glucose and sodium L-[U- 14 C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly higher blood glucose and lactate concentrations than controls. The iron-deficient group had a significantly higher glucose turnover rate than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14 C into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover rates between deficient rats and controls was attributed to 14 C recycling. The results indicate a greater dependence on glucose metabolism in iron-deficient rats

Glycogenomics as a mass spectrometry-guided genome-mining method for microbial glycosylated molecules.

Science.gov (United States)

Kersten, Roland D; Ziemert, Nadine; Gonzalez, David J; Duggan, Brendan M; Nizet, Victor; Dorrestein, Pieter C; Moore, Bradley S

2013-11-19

Glycosyl groups are an essential mediator of molecular interactions in cells and on cellular surfaces. There are very few methods that directly relate sugar-containing molecules to their biosynthetic machineries. Here, we introduce glycogenomics as an experiment-guided genome-mining approach for fast characterization of glycosylated natural products (GNPs) and their biosynthetic pathways from genome-sequenced microbes by targeting glycosyl groups in microbial metabolomes. Microbial GNPs consist of aglycone and glycosyl structure groups in which the sugar unit(s) are often critical for the GNP's bioactivity, e.g., by promoting binding to a target biomolecule. GNPs are a structurally diverse class of molecules with important pharmaceutical and agrochemical applications. Herein, O- and N-glycosyl groups are characterized in their sugar monomers by tandem mass spectrometry (MS) and matched to corresponding glycosylation genes in secondary metabolic pathways by a MS-glycogenetic code. The associated aglycone biosynthetic genes of the GNP genotype then classify the natural product to further guide structure elucidation. We highlight the glycogenomic strategy by the characterization of several bioactive glycosylated molecules and their gene clusters, including the anticancer agent cinerubin B from Streptomyces sp. SPB74 and an antibiotic, arenimycin B, from Salinispora arenicola CNB-527.

Determination Of Ph Including Hemoglobin Correction

Science.gov (United States)

Maynard, John D.; Hendee, Shonn P.; Rohrscheib, Mark R.; Nunez, David; Alam, M. Kathleen; Franke, James E.; Kemeny, Gabor J.

2005-09-13

Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

Isotope effects in the non enzymic glycation of hemoglobin catalyzed by DPG

International Nuclear Information System (INIS)

Gil, Herminia; Uzcategui, Jorge

1993-01-01

The paradigmatic reaction of glucose with hemoglobin (Hb A o ) has been studied and is known to occur most rapidly at the N-terminal valine of the β-subunit. An initial, rapid imine formation is succeeded by slower Amadori rearrangement. Non enzymic glycation of Hb A o was studied in vitro in buffer Tris 10 mM in H 2 O and D 2 O, pH 7.3, pD 7.8 at 37 deg C at a fixed concentration of 2,3 diphosphoglycerate (DPG). The reaction exhibits identical rates in protium and deuterium oxides. When D-glucose-2-h is compared with D-glucose-2-d, the kinetic isotope effect for the DPG-dependent rate is 2.1 ± 0.3, while the DPG-independent rate constant shows no isotope effect (1.1 ± 0.1). The absence of a rate in isotopic water solvents shows that proton donation for solvent, lyons or DPG does not limit the rate. The substrate isotope effect of around 2 for the DPG kinetic term indicates that the proton abstraction step of the Amadori rearrangement by DPG is wholly or partially rate-limiting for this reaction. (author)

A Retrospective Mid- and Long-term Follow-up Study on the Changes in Hematologic Parameters in the Highly Exposed Residents of the Hebei Spirit Oil Spill in Taean, South Korea

Science.gov (United States)

Choi, Young-Hyun; Hong, Jee-Young; Lee, Moo-Sik

2017-01-01

Objectives This study aimed to analyze changes in hematologic parameters in the residents of the areas highly contaminated by the Hebei Spirit Oil Spill in 2007 and those who participated in the clean-up activities. Methods According to demographic characteristics, health status and behavior, and level of exposure to oil, we compared the hematologic results in 2009 and 2012 among 701 residents. The hematologic parameters were composed of white blood cell (WBC) count, and levels of hemoglobin, hematocrit (Hct), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine (Cr), total cholesterol (T-chol), high-density lipoprotein (HDL), and triglyceride (TG). Results Paired t-test revealed that the WBC count and levels of Hct, AST, ALT, glucose, and HbA1c significantly increased, whereas the BUN, Cr, HDL, and TG levels significantly decreased. Multiple linear regression modelling showed a relationship between the level of exposure to oil and temporal changes in Hct, glucose, HbA1c, and BUN levels. Conclusion Our results suggest a relationship between level of exposure to oil and changes in hematologic parameters over 3 years. Further studies should be conducted to determine the impact of oil spill on health such as the occurrence of diseases. PMID:29164048

Wushenziye Formula Improves Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus via PTP1B-IRS1-Akt-GLUT4 Signaling Pathway.

Science.gov (United States)

Tian, Chunyu; Chang, Hong; La, Xiaojin; Li, Ji-An

2017-01-01

Background. Wushenziye formula (WSZYF) is an effective traditional Chinese medicine in the treatment of type 2 diabetes mellitus (T2DM). Aim. This study aimed to identify the effects and underlying mechanisms of WSZYF on improving skeletal muscle insulin resistance in T2DM. Methods. An animal model of T2DM was induced by Goto-Kakizaki diabetes prone rats fed with high fat and sugar for 4 weeks. Insulin resistance model was induced in skeletal muscle cell. Results. In vivo , WSZYF improved general conditions and decreased significantly fasting blood glucose, glycosylated serum protein, glycosylated hemoglobin, insulin concentration, and insulin resistance index of T2DM rats. In vitro , WSZYF enhanced glucose consumption in insulin resistance model of skeletal muscle cell. Furthermore, WSZYF affected the expressions of molecules in regulating T2DM, including increasing the expressions of p-IRS1, p-Akt, and GLUT4, reducing PTP1B expression. Conclusion . These findings displayed the potential of WSZYF as a new drug candidate in the treatment of T2DM and the antidiabetic mechanism of WSZYF is probably mediated through modulating the PTP1B-IRS1-Akt-GLUT4 signaling pathway.

Wushenziye Formula Improves Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus via PTP1B-IRS1-Akt-GLUT4 Signaling Pathway

Directory of Open Access Journals (Sweden)

Chunyu Tian

2017-01-01

Full Text Available Background. Wushenziye formula (WSZYF is an effective traditional Chinese medicine in the treatment of type 2 diabetes mellitus (T2DM. Aim. This study aimed to identify the effects and underlying mechanisms of WSZYF on improving skeletal muscle insulin resistance in T2DM. Methods. An animal model of T2DM was induced by Goto-Kakizaki diabetes prone rats fed with high fat and sugar for 4 weeks. Insulin resistance model was induced in skeletal muscle cell. Results. In vivo, WSZYF improved general conditions and decreased significantly fasting blood glucose, glycosylated serum protein, glycosylated hemoglobin, insulin concentration, and insulin resistance index of T2DM rats. In vitro, WSZYF enhanced glucose consumption in insulin resistance model of skeletal muscle cell. Furthermore, WSZYF affected the expressions of molecules in regulating T2DM, including increasing the expressions of p-IRS1, p-Akt, and GLUT4, reducing PTP1B expression. Conclusion. These findings displayed the potential of WSZYF as a new drug candidate in the treatment of T2DM and the antidiabetic mechanism of WSZYF is probably mediated through modulating the PTP1B-IRS1-Akt-GLUT4 signaling pathway.

Hemoglobin estimation by the HemoCue® portable hemoglobin photometer in a resource poor setting.

Science.gov (United States)

Nkrumah, Bernard; Nguah, Samuel Blay; Sarpong, Nimako; Dekker, Denise; Idriss, Ali; May, Juergen; Adu-Sarkodie, Yaw

2011-04-21

In resource poor settings where automated hematology analyzers are not available, the Cyanmethemoglobin method is often used. This method though cheaper, takes more time. In blood donations, the semi-quantitative gravimetric copper sulfate method which is very easy and inexpensive may be used but does not provide an acceptable degree of accuracy. The HemoCue® hemoglobin photometer has been used for these purposes. This study was conducted to generate data to support or refute its use as a point-of-care device for hemoglobin estimation in mobile blood donations and critical care areas in health facilities. EDTA blood was collected from study participants drawn from five groups: pre-school children, school children, pregnant women, non-pregnant women and men. Blood collected was immediately processed to estimate the hemoglobin concentration using three different methods (HemoCue®, Sysmex KX21N and Cyanmethemoglobin). Agreement between the test methods was assessed by the method of Bland and Altman. The Intraclass correlation coefficient (ICC) was used to determine the within subject variability of measured hemoglobin. Of 398 subjects, 42% were males with the overall mean age being 19.4 years. The overall mean hemoglobin as estimated by each method was 10.4 g/dl for HemoCue, 10.3 g/dl for Sysmex KX21N and 10.3 g/dl for Cyanmethemoglobin. Pairwise analysis revealed that the hemoglobin determined by the HemoCue method was higher than that measured by the KX21N and Cyanmethemoglobin. Comparing the hemoglobin determined by the HemoCue to Cyanmethemoglobin, the concordance correlation coefficient was 0.995 (95% CI: 0.994-0.996, p < 0.001). The Bland and Altman's limit of agreement was -0.389 - 0.644 g/dl with the mean difference being 0.127 (95% CI: 0.102-0.153) and a non-significant difference in variability between the two measurements (p = 0.843). After adjusting to assess the effect of other possible confounders such as sex, age and category of person, there was no

Nonlinear photoacoustic spectroscopy of hemoglobin

Energy Technology Data Exchange (ETDEWEB)

Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V., E-mail: LHWANG@WUSTL.EDU [Optical Imaging Laboratory, Department of Biomedical Engineering, Washington University in St. Louis, One Brookings Drive, St. Louis, Missouri 63130 (United States)

2015-05-18

As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

Nonlinear photoacoustic spectroscopy of hemoglobin.

Science.gov (United States)

Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P; Xia, Jun; Wang, Lihong V

2015-05-18

As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

Nonlinear photoacoustic spectroscopy of hemoglobin

International Nuclear Information System (INIS)

Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V.

2015-01-01

As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography

The effect of glycosylation on cytotoxicity of Ibaraki virus nonstructural protein NS3

Science.gov (United States)

URATA, Maho; WATANABE, Rie; IWATA, Hiroyuki

2015-01-01

The cytotoxicity of Ibaraki virus nonstructural protein NS3 was confirmed, and the contribution of glycosylation to this activity was examined by using glycosylation mutants of NS3 generated by site-directed mutagenesis. The expression of NS3 resulted in leakage of lactate dehydrogenase to the culture supernatant, suggesting the cytotoxicity of this protein. The lack of glycosylation impaired the transport of NS3 to the plasma membrane and resulted in reduced cytotoxicity. Combined with the previous observation that NS3 glycosylation was specifically observed in mammalian cells (Urata et al., Virus Research 2014), it was suggested that the alteration of NS3 cytotoxicity through modulating glycosylation is one of the strategies to achieve host specific pathogenisity of Ibaraki virus between mammals and vector arthropods. PMID:26178820

Serum 25(OH)D and Type 2 Diabetes Association in a General Population

DEFF Research Database (Denmark)

Husemoen, Lise-Lotte; Thuesen, Betina H; Fenger, Mogens

2012-01-01

OBJECTIVEThis study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis.RESEARCH DESIGN AND METHODSA random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6......,405 men and women aged 30-65 years at baseline (1999-2001), with 4,296 participating in the follow-up examination 5 years later (2004-2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated...... hemoglobin (HbA(1c)) test. Secondary outcomes included continuous markers of glucose homeostasis.RESULTSThe risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84-0.97) in crude analyses. The association became statistically nonsignificant after...

N-Glycosylation of Carnosinase Influences Protein Secretion and Enzyme Activity Implications for Hyperglycemia

NARCIS (Netherlands)

Riedl, Eva; Koeppel, Hannes; Pfister, Frederick; Peters, Verena; Sauerhoefer, Sibylle; Sternik, Paula; Brinkkoetter, Paul; Zentgraf, Hanswalter; Navis, Gerjan; Henning, Robert H.; Van Den Born, Jacob; Bakker, Stephan J. L.; Janssen, Bart; van der Woude, Fokko J.; Yard, Benito A.

OBJECTIVE-The (CTG)(n) polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1

effect of extreme seasonal variations and environments on some stress hormones and clotting factors of type 2 diabetics

International Nuclear Information System (INIS)

Mohamed, A.I.

2006-01-01

the present study aimed to to investigate the effect of seasons (summer and winter) and environments (Cairo and Assiut) on some serum components including fasting and postprandial blood glucose, glycosylated hemoglobin cholesterol and triglycerides in type Il diabetic patients . measure also included prothrombin time, partial thromboplastin time, plasma fibrinogen, factor Vlll and plasminogen . the study also aimed to investigate the effect of season and environments on serum insulin, glucagon, cortisol and prolactin. twenty male diabetics and ten normal control have shared from each governorate during summer and winter. data from this study showed: 1- during summer, there was an increase in postprandial glucose of normal volunteers and in fasting and postprandial glucose in cairo diabetics. 2- normal assiut volunteers experienced increased FBG in summer while diabetics experienced lower postprandial glucose during summer. 3- during winter, cairo diabetics had significantly lower fasting and postprandial glucose than assiut diabetics.4- during summer, cairo diabetics had increased postprandial serum glucose in comparison to assiut. 5-the more the level of glucose the less the effect of seasons on blood glucose. 6- serum triglycerides were higher in cairo during summer, while serum cholesterol was higher in assiut in summer than in winter

Metabolic control in patients with type 2 diabetes mellitus in a public hospital in Peru: a cross-sectional study in a low-middle income country.

Science.gov (United States)

Huayanay-Espinoza, Irma Elizabeth; Guerra-Castañon, Felix; Lazo-Porras, María; Castaneda-Guarderas, Ana; Thomas, Nimmy Josephine; Garcia-Guarniz, Ana-Lucia; Valdivia-Bustamante, Augusto A; Málaga, Germán

2016-01-01

The objective of this study was to assess patients' achievement of ADA (American Diabetes Association) guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM) outpatient clinic in a low-middle income country (LMIC) setting. This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c), and lipid profile. Laboratory parameters and blood pressure were evaluated according to ADA recommendations. Of the 123 patients, 81 were women and the mean age was 61.8 years. Glycemic control was abnormal in 82 (68.33%) participants, and 45 (37.50%) were unable to control their blood pressure. Lipid profile was abnormal in 73 (60.83%) participants. Only nine (7.50%) participants fulfilled ADA recommendations for glycemic, blood pressure, and lipid control. Amongst individuals with type 2 diabetes, there was poor attainment of the ADA recommendations (HbA1c, blood pressure and LDL-cholesterol) for ambulatory T2DM patients. Interventions are urgently needed in order to prevent long-term diabetic complications.

Association between metabolic control and oral health in adolescents with type 1 diabetes mellitus.

Science.gov (United States)

Saes Busato, Ivana Maria; Bittencourt, Mônica Sommer; Machado, Maria Angela Naval; Grégio, Ana Maria Trindade; Azevedo-Alanis, Luciana Reis

2010-03-01

The aim of this study was to evaluate the association between metabolic control and oral health of adolescents with type 1 diabetes mellitus (DM1). A case-control epidemiologic study was performed on adolescents allocated between 2 groups: DM1 group composed of 51 with DM1, and control group composed of 51 without diabetes. In the DM1 group, metabolic control data were observed (glycosylated hemoglobin (GHb) and capillary glucose), whereby GHb 8.0% poor metabolic control (DM1-B). Oral mucosal abnormalites, Community Periodontal Index (CPI), and decayed, missing, and filled (DMF) index were documented. Salivary flow was evaluated by means of stimulated saliva collection (SSFR). Glycosylated hemoglobin values of 8.0% (DM1-B) in 34 (76%) of the subjects. The average DMF indexes were 1.5 (control) and 3.3 (DM1-group) (P < or = .05). The average CPIs were 0.2 (control), 1.4 (DM1-A), and 2.0 (DM1-B) (P < or = .05). Average SSFRs were 0.997 (DM1-A), 0.903 (DM1-B), and 1.224 (control) mL/min. Oral health of adolescents with DM1 was impaired regardless of metabolic control. Copyright 2010 Mosby, Inc. All rights reserved.

Cancer associated aberrant protein o-glycosylation can modify antigen processing and immune response

DEFF Research Database (Denmark)

Madsen, Caroline B; Petersen, Cecilie; Lavrsen, Kirstine

2012-01-01

Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing......, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo...

Hemoglobin Variants: Biochemical Properties and Clinical Correlates

Science.gov (United States)

Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

2013-01-01

Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

Rapid phenolic O-glycosylation of small molecules and complex unprotected peptides in aqueous solvent

Science.gov (United States)

Wadzinski, Tyler J.; Steinauer, Angela; Hie, Liana; Pelletier, Guillaume; Schepartz, Alanna; Miller, Scott J.

2018-06-01

Glycosylated natural products and synthetic glycopeptides represent a significant and growing source of biochemical probes and therapeutic agents. However, methods that enable the aqueous glycosylation of endogenous amino acid functionality in peptides without the use of protecting groups are scarce. Here, we report a transformation that facilitates the efficient aqueous O-glycosylation of phenolic functionality in a wide range of small molecules, unprotected tyrosine, and tyrosine residues embedded within a range of complex, fully unprotected peptides. The transformation, which uses glycosyl fluoride donors and is promoted by Ca(OH)2, proceeds rapidly at room temperature in water, with good yields and selective formation of unique anomeric products depending on the stereochemistry of the glycosyl donor. High functional group tolerance is observed, and the phenol glycosylation occurs selectively in the presence of virtually all side chains of the proteinogenic amino acids with the singular exception of Cys. This method offers a highly selective, efficient, and operationally simple approach for the protecting-group-free synthesis of O-aryl glycosides and Tyr-O-glycosylated peptides in water.

Changes in the pharmacokinetics of teicoplanin in patients with hyperglycaemic hypoalbuminaemia: Impact of albumin glycosylation on the binding of teicoplanin to albumin.

Science.gov (United States)

Enokiya, Tomoyuki; Muraki, Yuichi; Iwamoto, Takuya; Okuda, Masahiro

2015-08-01

There is large interindividual variability in serum teicoplanin (TEIC) concentrations after administration of a loading dose, and the factors that influence the pharmacokinetics of TEIC are disputed. The aim of this study was to clarify changes in the pharmacokinetics of TEIC that occur in patients with hyperglycaemia as well as the impact of albumin glycosylation on the pharmacokinetics of TEIC. This study consisted of retrospective and prospective investigations. The pharmacokinetic parameters of TEIC were retrospectively compared between patients receiving TEIC treatment. Ninety-four patients were divided into four groups according to their serum albumin and blood glucose concentrations [(i) hyperglycaemic hypoalbuminaemia (albuminalbumin≥3.0g/dL) (n=9); and (iv) non-hyperglycaemic normoalbuminaemia (n=40)]. In addition, the concentration of glycosylated albumin was prospectively determined in 28 patients. At 12h after administration of a loading dose, patients with hyperglycaemic hypoalbuminaemia displayed significantly lower serum TEIC concentrations (Palbumin was significantly correlated with the association constant (Ka) of TEIC for albumin (r=0.53, P=0.004) and the Vd (r=0.41, P=0.031). These results suggest that hyperglycaemic hypoalbuminaemia lowers the serum TEIC concentration, which is attributable to the decreased Ka and increased Vd of TEIC by albumin glycosylation. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

High affinity hemoglobin and Parkinson's disease.

Science.gov (United States)

Graham, Jeffrey; Hobson, Douglas; Ponnampalam, Arjuna

2014-12-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain. Oxidative damage in this region has been shown to play an important role in the pathogenesis of this disease. Human neurons have been discovered to contain hemoglobin, with an increased concentration seen in the neurons of the SN. High affinity hemoglobin is a clinical entity resulting from mutations that create a functional increase in the binding of hemoglobin to oxygen and an inability to efficiently unload it to tissues. This can result in a number of metabolic compensatory changes, including an elevation in circulating hemoglobin and an increase in the molecule 2,3-diphosphoglycerate (2,3-DPG). Population based studies have revealed that patients with PD have elevated hemoglobin as well as 2,3-DPG levels. Based on these observations, we hypothesize that the oxidative damage seen in PD is related to an underlying high affinity hemoglobin subtype. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Conformation analysis of the N-glycosylation site Asn-X-Thr/Ser in glycoproteins].

Science.gov (United States)

Avanov, A Ia; Lipkind, G M

1990-03-01

Theoretical conformational analysis of oligopeptides CH3CO-Asn-X-Thr-NHCH3 (X = Gly, Ala, Pro), modelling N-glycosylation site, and their glycosylated derivatives CH3CO-(GlcNAc beta 1-4GlcNAc beta 1) Asn-X-Thr-NHCH3 has been carried out. Active conformations of the site are found, corresponding to structural prerequisities of N-glycosylation: Asn residue's position in beta-turn and hydrogen bond formation between side chains of Asn and Thr/Ser residues. In this case the L conformation of the central residue X is most probable. Since Pro residue does not possess this conformation, sequences with X = Pro are not glycosylated. It is shown that glycosylation of the above-mentioned sites is accompanied by reorientation of the Asn residue's side chains.

Cancer cell spheroids are a better screen for the photodynamic efficiency of glycosylated photosensitizers.

Directory of Open Access Journals (Sweden)

Patrícia M R Pereira

Full Text Available Photodynamic Therapy (PDT relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To date, in vitro PDT efficacy is mostly screened using two-dimensional monolayer cultures. Compared to monolayer cultures, three-dimensional spheroid cultures have unique spatial distributions of nutrients, metabolites, oxygen and signalling molecules; therefore better mimic in vivo conditions. We obtained 0.05 mm3 spheroids with four different human tumor cell lines (HCT-116, MCF-7, UM-UC-3 and HeLa with appropriate sizes for screening PDT agents. We observed that detachment from monolayer culture and growth as tumor spheroids was accompanied by changes in glucose metabolism, endogenous ROS levels, galectin-1 and glucose transporter GLUT1 protein levels. We compared the phototoxic responses of a porphyrin conjugated with four glucose molecules (PorGlu4 in monolayer and spheroid cultures. The uptake and phototoxicity of PorGlu4 is highly dependent on the monolayer versus spheroid model used and on the different levels of GLUT1 protein expressed by these in vitro platforms. This study demonstrates that HCT-116, MCF-7, UM-UC-3 and HeLa spheroids afford a more rational platform for the screening of new glycosylated-photosensitizers compared to monolayer cultures of these cancer cells.

A computational framework for the automated construction of glycosylation reaction networks.

Science.gov (United States)

Liu, Gang; Neelamegham, Sriram

2014-01-01

Glycosylation is among the most common and complex post-translational modifications identified to date. It proceeds through the catalytic action of multiple enzyme families that include the glycosyltransferases that add monosaccharides to growing glycans, and glycosidases which remove sugar residues to trim glycans. The expression level and specificity of these enzymes, in part, regulate the glycan distribution or glycome of specific cell/tissue systems. Currently, there is no systematic method to describe the enzymes and cellular reaction networks that catalyze glycosylation. To address this limitation, we present a streamlined machine-readable definition for the glycosylating enzymes and additional methodologies to construct and analyze glycosylation reaction networks. In this computational framework, the enzyme class is systematically designed to store detailed specificity data such as enzymatic functional group, linkage and substrate specificity. The new classes and their associated functions enable both single-reaction inference and automated full network reconstruction, when given a list of reactants and/or products along with the enzymes present in the system. In addition, graph theory is used to support functions that map the connectivity between two or more species in a network, and that generate subset models to identify rate-limiting steps regulating glycan biosynthesis. Finally, this framework allows the synthesis of biochemical reaction networks using mass spectrometry (MS) data. The features described above are illustrated using three case studies that examine: i) O-linked glycan biosynthesis during the construction of functional selectin-ligands; ii) automated N-linked glycosylation pathway construction; and iii) the handling and analysis of glycomics based MS data. Overall, the new computational framework enables automated glycosylation network model construction and analysis by integrating knowledge of glycan structure and enzyme biochemistry. All

A computational framework for the automated construction of glycosylation reaction networks.

Directory of Open Access Journals (Sweden)

Gang Liu

Full Text Available Glycosylation is among the most common and complex post-translational modifications identified to date. It proceeds through the catalytic action of multiple enzyme families that include the glycosyltransferases that add monosaccharides to growing glycans, and glycosidases which remove sugar residues to trim glycans. The expression level and specificity of these enzymes, in part, regulate the glycan distribution or glycome of specific cell/tissue systems. Currently, there is no systematic method to describe the enzymes and cellular reaction networks that catalyze glycosylation. To address this limitation, we present a streamlined machine-readable definition for the glycosylating enzymes and additional methodologies to construct and analyze glycosylation reaction networks. In this computational framework, the enzyme class is systematically designed to store detailed specificity data such as enzymatic functional group, linkage and substrate specificity. The new classes and their associated functions enable both single-reaction inference and automated full network reconstruction, when given a list of reactants and/or products along with the enzymes present in the system. In addition, graph theory is used to support functions that map the connectivity between two or more species in a network, and that generate subset models to identify rate-limiting steps regulating glycan biosynthesis. Finally, this framework allows the synthesis of biochemical reaction networks using mass spectrometry (MS data. The features described above are illustrated using three case studies that examine: i O-linked glycan biosynthesis during the construction of functional selectin-ligands; ii automated N-linked glycosylation pathway construction; and iii the handling and analysis of glycomics based MS data. Overall, the new computational framework enables automated glycosylation network model construction and analysis by integrating knowledge of glycan structure and enzyme

Characteristic emission in glutaraldehyde polymerized hemoglobin

International Nuclear Information System (INIS)

Ma Li; Wang Xiaojun

2011-01-01

Hemoglobin with different modifications has been investigated using spectroscopic techniques. A new emission at around 371 nm has been observed under excitation of 305 nm from glutaraldehyde polymerized human hemoglobin. Intensity and peak position of the emission are dependent on both oxidation state and ligand environment and the emission has been identified from the hemoglobin oligomer.

Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans.

Science.gov (United States)

List, James F; Whaley, Jean M

2011-03-01

Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.

Is type 2 diabetes really resolved after laparoscopic sleeve gastrectomy? Glucose variability studied by continuous glucose monitoring.

Science.gov (United States)

Capoccia, D; Coccia, F; Guida, A; Rizzello, M; De Angelis, F; Silecchia, G; Leonetti, F

2015-01-01

The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (<140 mg/dL) at 120 minutes OGTT. These interesting data could help clinicians to better individualize patients in which diabetes is not resolved and who could need more attention in order to prevent chronic complications of diabetes.

Role of prediabetes in stroke

Science.gov (United States)

Mijajlović, Milija D; Aleksić, Vuk M; Šternić, Nadežda M; Mirković, Mihailo M; Bornstein, Natan M

2017-01-01

Stroke is one of the leading causes of death and probably the greatest cause of adult disability worldwide. Diabetes mellitus (DM) is a state of accelerated aging of blood vessels. Patients with diabetes have increased risk of stroke. Hyperglycemia represents a risk factor for poor outcome following stroke, and probably is just a marker of poor outcome rather than a cause. Lowering of blood glucose levels has not been shown to improve prognosis. Also, prevention of stroke risk among patients with DM is not improved with therapy for reduction of glucose levels. On the other hand, prediabetes, a metabolic state between normal glucose metabolism and diabetes, is a risk factor for the development of DM type 2 and subsequently for stroke. Several methods are known to identify prediabetes patients, including fasting plasma glucose levels, 2-hour post load glucose levels, and glycosylated hemoglobin levels. In this text, we tried to summarize known data about diagnosis, epidemiology, risk factors, pathophysiology, and prevention of prediabetes in relation to DM and stroke. PMID:28203079

Continuous glucose monitoring for patients with diabetes: an evidence-based analysis.

Science.gov (United States)

2011-01-01

sensor is required. The device is equipped with alarms which warn the patient of impending hypo-or hyperglycemia. Two types of CGM are available: Systems that is stored in a monitor and can be downloaded later.Real time systems that continuously provide the actual glucose concentration on a display. What is the effectiveness and cost-effectiveness of CGM combined with SMBG compared with SMBG alone in the management of diabetes? A literature search was performed on September 15, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2002 until September 15, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. English languageRandomized controlled trials (N>30 patients)Adults or pediatric patients with insulin dependent diabetes (type 1 or 2 or gestational)Studies comparing CGM plus SMBG versus SMBG alone Case studiesStudies that did not compare CGM plus SMBG versus SMBG aloneStudies that did not report statistical analysis of outcomes or data was unextractable Change in glycosylated hemoglobin (HbA1c)Frequency or duration of hypo-or hyperglycemic episodes or euglycemiaAdverse effects Moderate quality evidence that CGM + SMBG: is not more effective than self monitoring of blood glucose (SMBG) alone in the reduction of HbA1c using insulin infusion pumps for Type 1 diabetes.is not more effective than SMBG

Cell Surface Glycosylation Is Required for Efficient Mating of Haloferax volcanii

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Yarden Shalev

2017-07-01

Full Text Available Halophilic archaea use a fusion-based mating system for lateral gene transfer across cells, yet the molecular mechanisms involved remain unknown. Previous work implied that cell fusion involves cell–cell recognition since fusion occurs more efficiently between cells from the same species. Long believed to be restricted only to Eukarya, it is now known that cells of all three domains of life perform N-glycosylation, the covalent attachment of glycans to select target asparagine residues in proteins, and that this post-translational modification is common for archaeal cell surface proteins. Here, we show that differences in glycosylation of the Haloferax volcanii surface-layer glycoprotein, brought about either by changing medium salinity or by knocking out key glycosylation genes, reduced mating success. Thus, different glycosylation patterns are likely to underlie mating preference in halophilic archaea, contributing to speciation processes.

Radio-ligand immunoassay for human hemoglobin variants

International Nuclear Information System (INIS)

Javid, J.; Pettis, P.K.; Miller, J.E.

1981-01-01

A quantitative method is described for the individual assay of human hemoglobin variants occurring singly or in mixture. The hemoglobin to be assayed is bound to specific antibody; the immune complex is attached to protein A-containing S. aureus and removed from the mixture. The hemoglobin thus isolated is quantified by its ability to bind radiolabeled haptoglobin. The technique is accurate and distinguishes among the 4 hemoglobins tested, namely Hb A, S, C and F. It has the advantage over conventional radioimmunoassay that a single probe, radiolabeled haptoglobin, is needed for the specific assay of any hemoglobin. (Auth.)

Oxygen Measurements in Liposome Encapsulated Hemoglobin

Science.gov (United States)

Phiri, Joshua Benjamin

Liposome encapsulated hemoglobins (LEH's) are of current interest as blood substitutes. An analytical methodology for rapid non-invasive measurements of oxygen in artificial oxygen carriers is examined. High resolution optical absorption spectra are calculated by means of a one dimensional diffusion approximation. The encapsulated hemoglobin is prepared from fresh defibrinated bovine blood. Liposomes are prepared from hydrogenated soy phosphatidylcholine (HSPC), cholesterol and dicetylphosphate using a bath sonication method. An integrating sphere spectrophotometer is employed for diffuse optics measurements. Data is collected using an automated data acquisition system employing lock-in -amplifiers. The concentrations of hemoglobin derivatives are evaluated from the corresponding extinction coefficients using a numerical technique of singular value decomposition, and verification of the results is done using Monte Carlo simulations. In situ measurements are required for the determination of hemoglobin derivatives because most encapsulation methods invariably lead to the formation of methemoglobin, a nonfunctional form of hemoglobin. The methods employed in this work lead to high resolution absorption spectra of oxyhemoglobin and other derivatives in red blood cells and liposome encapsulated hemoglobin (LEH). The analysis using singular value decomposition method offers a quantitative means of calculating the fractions of oxyhemoglobin and other hemoglobin derivatives in LEH samples. The analytical methods developed in this work will become even more useful when production of LEH as a blood substitute is scaled up to large volumes.

A Novel Strategy for Characterization of Glycosylated Proteins Separated by Gel Electrophoresis

DEFF Research Database (Denmark)

Larsen, Martin; Skottrup, Peter; Enghild, Jan Johannes

Protein glycosylation can be vital for changing the function or physiochemical properties of a protein. Abnormal glycosylation can lead to protein malfunction, resulting in severe diseases. Therefore, it is important to develop techniques for characterization of such modifications in proteins...... graphite powder micro-columns in combination with mass spectrometry. The method is faster and more sensitive than previous approaches and would be ideal for proteomics studies and verification of correct glycosylation of recombinant glycoproteins....

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

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Seyed Ali Mousavi

2015-01-01

Full Text Available Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L baseline hemoglobin were compared with those with lower (<138 g/L baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations.

Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes

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Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

2015-01-01

Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

HEK293T cell lines defective for O-linked glycosylation.

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James M Termini

Full Text Available Here we describe derivatives of the HEK293T cell line that are defective in their ability to generate mucin-type O-linked glycosylation. Using CRISPR/Cas9 and a single-cell GFP-sorting procedure, the UDP-galactose-4-epimerase (GALE, galactokinase 1 (GALK1, and galactokinase 2 (GALK2 genes were knocked out individually and in combinations with greater than 90% of recovered clones having the desired mutations. Although HEK293T cells are tetraploid, we found this approach to be an efficient method to target and disrupt all 4 copies of the target gene. Deficient glycosylation in the GALE knockout cell line could be rescued by the addition of galactose and N-acetylgalactosamine (GalNAc to the cell culture media. However, when key enzymes of the galactose/GalNAc salvage pathways were disrupted in tandem (GALE+GALK1 or GALE+GALK2, O-glycosylation was eliminated and could not be rescued by the addition of either galactose plus GalNAc or UDP-galactose plus UDP-GalNAc. GALK1 and GALK2 are key enzymes of the galactose/GalNAc salvage pathways. Mass spectrometry was performed on whole cell lysate of the knockout cell lines to verify the glycosylation phenotype. As expected, the GALE knockout was almost completely devoid of all O-glycosylation, with minimal glycosylation as a result of functional salvage pathways. However, the GALE+GALK1 and GALE+GALK2 knockout lines were devoid of all O-glycans. Mass spectrometry analysis revealed that the disruption of GALE, GALK1, and GALE+GALK2 had little effect on the N-glycome. But when GALE was knocked out in tandem with GALK1, N-glycans were exclusively of the high mannose type. Due to the well-characterized nature of these five knockout cell lines, they will likely prove useful for a wide variety of applications.

Glycated Hemoglobin Levels in Patients with Decompensated Cirrhosis

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Jeffrey Nadelson

2016-01-01

Full Text Available Introduction. Aim of this study is to determine if HbA1c levels are a reliable predictor of glycemic control in patients with decompensated cirrhosis. Methods. 200 unique patients referred for liver transplantation at University of Tennessee/Methodist University Transplant Institute with a HbA1c result were included. Three glucose levels prior to the “measured” A1c (MA1c were input into an HbA1c calculator from the American Diabetes Association website to determine the “calculated” A1c (CA1c. The differences between MA1c and CA1c levels were computed. Patients were divided into three groups: group A, difference of 1.5. Results. 97 (49% patients had hemoglobin A1c of less than 5%. Discordance between calculated and measured HbA1c of >0.5% was seen in 47% (n=94. Higher level of discordance of greater than >1.5 was in 12% of patients (n=24. Hemoglobin was an independent predictor for higher discordance (odds ratio 0.77 95%, CI 0.60–0.99, and p value 0.04. HbA1c was an independent predictor of occurrence of HCC (OR 2.69 955, CI 1.38–5.43, and p value 0.008. Conclusion. HbA1c is not a reliable predictor of glycemic control in patients with decompensated cirrhosis, especially in those with severe anemia.

Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.

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Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry

2015-05-01

Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.

A review of variant hemoglobins interfering with hemoglobin A1c measurement.

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Little, Randie R; Roberts, William L

2009-05-01

Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

Model-based analysis of N-glycosylation in Chinese hamster ovary cells

DEFF Research Database (Denmark)

Krambeck, Frederick J.; Bennun, Sandra V; Andersen, Mikael Rørdam

2017-01-01

The Chinese hamster ovary (CHO) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. The similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower...

Oxytocin analogues with O-glycosylated serine and threonine in position 4

Czech Academy of Sciences Publication Activity Database

Marcinkowska, A.; Borovičková, Lenka; Slaninová, Jiřina; Grzonka, Z.

2007-01-01

Roč. 81, č. 7 (2007), s. 1335-1344 ISSN 0137- 5083 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z90210515 Keywords : oxytocin * glycosylated serin * glycosylated threonin * position 4 Subject RIV: CE - Biochemistry Impact factor: 0.483, year: 2007

Micropinocytic ingestion of glycosylated albumin by isolated microvessels: possible role in pathogenesis of diabetic microangiopathy.

OpenAIRE

Williams, S K; Devenny, J J; Bitensky, M W

1981-01-01

Microvessels isolated from rat epididymal fat exhibit differential vesicular ingestion rates for unmodified and non-enzymatically glycosylated rat albumin. While unmodified rat albumin is excluded from ingestion by endothelial micropinocytic vesicles, glycosylated albumin is avidly taken up by endocytosis. Interaction of albumin and glycosylated albumin with endothelium was studied with a double-label fluorescence assay of micropinocytosis. When glycosylated albumin was present at a concentra...

Demographic details, clinical features, and nutritional characteristics of young adults with Type 1 diabetes mellitus - A South Indian tertiary center experience.

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Joseph, Mini; Shyamasunder, Asha H; Gupta, Riddhi D; Anand, Vijayalakshmi; Thomas, Nihal

2016-01-01

Type 1 diabetes mellitus (T1DM) accounts for 5-10% of all diagnosed diabetes and the highest incidence is found in India. The main objectives were to study the demographic, clinical, and nutritional characteristics of young adults with T1DM and its effect glycosylated hemoglobin levels. This cross-sectional study was conducted among young adults with T1DM (18-45 years of age) in a tertiary hospital in South India. Data were obtained from updated medical records. The dietary data were assessed from food diaries and 24 h recall method. Anthropometry was determined. The analysis revealed that socio-economic variables did not affect the glycosylated hemoglobin levels. The mean glycosylated hemoglobin value was 8.81 ± 2.38%. Nearly, half the patients were malnourished. The overall dietary intake was inadequate. The multivariate regression model, adjusted for confounding factors such as gender, age, and body mass index, revealed that only duration of diabetes and protein intake were significant predictors of glycosylated hemoglobin status ( P diabetes management. However, there is an urgent need to educate our patients on nutrition therapy. T1DM patients need specialized advice to ensure appropriately balanced nutrition that has a significant impact on their long-term glycemic control.

N-glycosylated catalytic unit meets O-glycosylated propeptide: complex protein architecture in a fungal hexosaminidase

Czech Academy of Sciences Publication Activity Database

Plíhal, Ondřej; Sklenář, Jan; Kmoníčková, J.; Man, Petr; Pompach, Petr; Havlíček, Vladimír; Křen, Vladimír; Bezouška, Karel

2004-01-01

Roč. 32, č. 5 (2004), s. 764-765 ISSN 0300-5127 R&D Projects: GA ČR GA203/04/1045 Institutional research plan: CEZ:AV0Z5020903 Keywords : asperillus oryzoe * glycosyl hydrolase * preproprotein Subject RIV: EE - Microbiology, Virology Impact factor: 2.267, year: 2004

Characterization of hemoglobin-benzo[a]pyrene adducts

International Nuclear Information System (INIS)

Haugen, D.A.; Myers, S.R.

1987-01-01

Cultures of Syrian hamster embryo (SHE) cells were supplemented with human Hb (0.2 mM heme) and [ 3 H]BP (1 μM). After a 24-h incubation, the medium was removed and subjected to cation-exchange liquid chromatography (CM-Sepharose) to resolve hemoglobins from serum proteins in the medium. The BP-treated Hb was subjected to analysis in each of three column chromatographic systems established for isolation and characterization of human hemoglobin and its genetic and post-translationally modified variants. Results demonstrate that hemoglobin-carcinogen adducts can be resolved from native hemoglobin by established conventional and high-performance liquid chromatographic procedures, suggesting the basis for development of general approaches for isolating and characterizing hemoglobin-carcinogen adducts. The results also suggest the basis for a model system in which adducts between carcinogens and human hemoglobin are formed in cultures of mammalian cells or tissues

In-depth mapping of the mouse brain N-glycoproteome reveals widespread N-glycosylation of diverse brain proteins.

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Fang, Pan; Wang, Xin-Jian; Xue, Yu; Liu, Ming-Qi; Zeng, Wen-Feng; Zhang, Yang; Zhang, Lei; Gao, Xing; Yan, Guo-Quan; Yao, Jun; Shen, Hua-Li; Yang, Peng-Yuan

2016-06-21

N-glycosylation is one of the most prominent and abundant posttranslational modifications of proteins. It is estimated that over 50% of mammalian proteins undergo glycosylation. However, the analysis of N-glycoproteins has been limited by the available analytical technology. In this study, we comprehensively mapped the N-glycosylation sites in the mouse brain proteome by combining complementary methods, which included seven protease treatments, four enrichment techniques and two fractionation strategies. Altogether, 13492 N-glycopeptides containing 8386 N-glycosylation sites on 3982 proteins were identified. After evaluating the performance of the above methods, we proposed a simple and efficient workflow for large-scale N-glycosylation site mapping. The optimized workflow yielded 80% of the initially identified N-glycosylation sites with considerably less effort. Analysis of the identified N-glycoproteins revealed that many of the mouse brain proteins are N-glycosylated, including those proteins in critical pathways for nervous system development and neurological disease. Additionally, several important biomarkers of various diseases were found to be N-glycosylated. These data confirm that N-glycosylation is important in both physiological and pathological processes in the brain, and provide useful details about numerous N-glycosylation sites in brain proteins.

Isotope effects in the non enzymic glycation of hemoglobin catalyzed by DPG

Energy Technology Data Exchange (ETDEWEB)

Gil, Herminia; Uzcategui, Jorge [Universidad de Los Andes, Merida (Venezuela). Dept. de Quimica

1993-12-31

The paradigmatic reaction of glucose with hemoglobin (Hb A{sub o}) has been studied and is known to occur most rapidly at the N-terminal valine of the {beta}-subunit. An initial, rapid imine formation is succeeded by slower Amadori rearrangement. Non enzymic glycation of Hb A{sub o} was studied in vitro in buffer Tris 10 mM in H{sub 2} O and D{sub 2} O, pH 7.3, pD 7.8 at 37 deg C at a fixed concentration of 2,3 diphosphoglycerate (DPG). The reaction exhibits identical rates in protium and deuterium oxides. When D-glucose-2-h is compared with D-glucose-2-d, the kinetic isotope effect for the DPG-dependent rate is 2.1 {+-} 0.3, while the DPG-independent rate constant shows no isotope effect (1.1 {+-} 0.1). The absence of a rate in isotopic water solvents shows that proton donation for solvent, lyons or DPG does not limit the rate. The substrate isotope effect of around 2 for the DPG kinetic term indicates that the proton abstraction step of the Amadori rearrangement by DPG is wholly or partially rate-limiting for this reaction. (author) 23 refs., 4 figs.

Fab glycosylation of immunoglobulin G does not associate with improvement of rheumatoid arthritis during pregnancy.

Science.gov (United States)

Bondt, Albert; Wuhrer, Manfred; Kuijper, T Martijn; Hazes, Johanna M W; Dolhain, Radboud J E M

2016-11-25

Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation. IgGs were captured from RA and control sera obtained before (RA only), during and after pregnancy, followed by Fc and Fab separation, glycan release, and mass spectrometric detection. In parallel, glycans from intact IgG were analysed. The data was used to calculate glycosylation traits, and to estimate the level of Fab glycosylation. The overall level of Fab glycosylation was increased in RA patients compared to controls, while no differences in Fab glycosylation patterns were found. For the Fc and intact IgG (Total) previously observed differences in galactosylation and bisection were confirmed. Furthermore, increased galactosylation of Fc and Total were associated with lower disease activity and autoantibody positivity. In addition, the change in Fc galactosylation associated with the change in disease activity during pregnancy and after delivery, while this was not the case for Fab. In contrast to changes in Fc glycosylation, changes in Fab glycosylation are not associated with improvement of RA during pregnancy and arthritis flare after delivery.

Therapeutic effects of entecavir and adefovir dipivoxil in hepatitis B cirrhosis patients with hepatogenous diabetes: a comparative analysis

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LI Na

2016-06-01

Full Text Available ObjectiveTo investigate the therapeutic effect of entecavir or adefovir dipivoxil as the antiviral therapy for hepatitis B cirrhosis patients with hepatogenous diabetes. MethodsA total of 80 hepatitis B cirrhosis patients with hepatogenous diabetes who visited Qingdao Hospital of Infectious Diseases were enrolled, and according to the antiviral drug they chose, they were divided into group A and group B, with 40 patients in each group. The patients in group A were treated with oral administration of entecavir 0.5 mg qd, and those in group B were treated with oral administration of adefovir dipivoxil 10 mg qd. The antiviral therapy lasted for 48 weeks. The patients in both groups were given diabetic diets and insulin to control blood glucose, as well as liver-protecting and transaminase-lowering treatments. The changes in biochemical parameters, viral response, diabetes control, and the improvement in liver stiffness after treatment were observed in both groups. The t-test was used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. ResultsThe viral response showed a significant difference between group A (85%, 34/40 and group B (65%, 26/40 (χ2=4.27, P＜0.05. Compared with group B, group A showed significant improvements in biochemical parameters (P＜0.05. After 48 weeks of treatment, group A had significantly lower levels of blood glucose and glycosylated hemoglobin than group B (blood glucose: 7.53±1.13 mmol/L vs 8.34±1.12 mmol/L, t=3.220, P＜0.05; glycosylated hemoglobin: 7.23%±0.64% vs 7.79%±084%, t=3.354; P＜0.05. After the treatment, liver stiffness showed a significant difference between group A and group B (16.86±5.67 kPa vs 19.47±5.32 kPa, t=2.123, P＜0.05. ConclusionCompared with adefovir dipivoxil, entecavir can improve glycogen metabolism and blood glucose regulation through improving liver function and promoting hepatocyte repair, and

Analysis of expression and glycosylation of avian metapneumovirus attachment glycoprotein from recombinant baculoviruses.

Science.gov (United States)

Luo, Lizhong; Nishi, Krista; MacLeod, Erin; Sabara, Marta I; Li, Yan

2010-11-01

Recently, we reported the expression and glycosylation of avian metapneumovirus attachment glycoprotein (AMPV/C G protein) in eukaryotic cell lines by a transient-expression method. In the present study, we investigated the biosynthesis and O-linked glycosylation of the AMPV/C G protein in a baculovirus expression system. The results showed that the insect cell-produced G protein migrated more rapidly in SDS-PAGE as compared to LLC-MK2 cell-derived G proteins owing to glycosylation differences. The fully processed, mature form of G protein migrated between 78 and 86 kDa, which is smaller than the 110 kDa mature form of G expressed in LLC-MK2 cells. In addition, several immature G gene products migrating at 40-48 and 60-70 kDa were also detected by SDS-PAGE and represented glycosylated intermediates. The addition of the antibiotic tunicamycin, which blocks early steps of glycosylation, to insect cell culture resulted in the disappearance of two glycosylated forms of the G protein and identified a 38 kDa unglycosylated precursor. The maturation of the G protein was completely blocked by monensin, suggesting that the O-linked glycosylation of G initiated in the trans-Golgi compartment. The presence of O-linked sugars on the mature protein was further confirmed by lectin Arachis hypogaea binding assay. Furthermore, antigenic features of the G protein expressed in insect cells were evaluated by ELISA. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

MR Imaging-derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities.

Science.gov (United States)

Avni, Reut; Golani, Ofra; Akselrod-Ballin, Ayelet; Cohen, Yonni; Biton, Inbal; Garbow, Joel R; Neeman, Michal

2016-07-01

Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging

N-Glycosylation optimization of recombinant antibodies in CHO cell through process and metabolic engineering

DEFF Research Database (Denmark)

Fan, Yuzhou

, analysis, control and optimization of N-glycosylation were thoroughly reviewed. In particular, how to control and optimize N-glycosylation in CHO cells was exclusively studied. The main focus of this PhD project is to find effective approaches of modulating N-glycosylation of CHO-derived recombinant...... galactose as feed additives, changing process parameters such as seeding density and cultivation duration are all demonstrated to be effective. The causal explanation of their impact on glycosylation can be various, including product, metabolism, proteome and physiology-associated mechanism. In the middle...... part of the thesis, both literature reviews and experimental applications were provided to demonstrate how to use omics data and implement systems biology to understand biological activities, especially N-glycosylation in CHO cells. In the last part of the thesis, the second strategy that apply genetic...

Effect of chicory seed extract on glucose tolerance test (GTT and metabolic profile in early and late stage diabetic rats

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Ali Ahadi

2012-10-01

Full Text Available Background and purpose of the study The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT and blood biochemical indices of experimentally-induced hyperglycemic rats.MethodsLate stage and early stage of Type 2 diabetes mellitus (T2DM were induced in rats by streptozotocin (STZ and a combination of STZ and niacinamide (NIA/STZ, respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days. Body weight and fasting blood sugar (FBS were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c and sera for alanine aminotransferase (ALT, aspartate aminotransferase (AST, nitric oxide (NO, triacylglycerol (TG, total cholesterol (TC, total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days.ResultsDuring 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p < 0.05. Unlike late-stage diabetes, fasting serum insulin concentrations were higher and GTT pattern approximated to normal in chicory-treated earlystage diabetic rats.ConclusionsChicory appeared to have short-term (about 2 hours, as far as GTT is concerned and longterm (28 days, in this study effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications.

Fulminant type 1 diabetes mellitus: a case report

Science.gov (United States)

Yunir, E.; Nenfiati

2018-03-01

Type 1 diabetes mellitus is a metabolic disease caused by insulin deficiency that results from destruction of β-cells in the pancreas. Based on American Diabetes Association, there are two types of type 1 diabetes mellitus: type 1A (autoimmune) and 1B (idiopathic). In this case, we are presenting a new archetype of type 1 diabetes named fulminant type 1 diabetes mellitus. This disease results from quick destruction of β-cells byanautoimmune mechanism. The manifestation of this disease consists of unspecific flu-like symptoms, abdominal symptoms, to specific hyperglycemia symptoms such as fatigue, malaise, change in mental status that are attributable to high blood glucose and ketosis. Laboratory examination reveals high blood glucose, normal glycosylated hemoglobin, ketosis or ketoacidosis, potassium depletion and elevation of liver function tests. Treatment consists of intravenous infusion followed by insulin injection for blood glucose control, followed by treatment of metabolic derangements such as acid-base and electrolyte disorder.

Enzymatic glycosylation of multivalent scaffolds

Czech Academy of Sciences Publication Activity Database

Bojarová, Pavla; Rosencrantz, R. R.; Elling, L.; Křen, Vladimír

2013-01-01

Roč. 42, č. 11 (2013), s. 4774-4797 ISSN 0306-0012 R&D Projects: GA MŠk(CZ) LD13042; GA ČR GAP207/10/0321 Institutional support: RVO:61388971 Keywords : N-ACETYLGLUCOSAMINYLTRANSFERASE-III * MUCIN TANDEM REPEAT * NEIGHBORING RESIDUE GLYCOSYLATION Subject RIV: CC - Organic Chemistry Impact factor: 30.425, year: 2013

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

Energy Technology Data Exchange (ETDEWEB)

Popp, R A; Stratton, L P; Hawley, D K; Effron, K [Oak Ridge National Lab., TN (USA)

1979-01-15

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F/sub 1/ offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of ..cap alpha..-chains normally found in all SEC mice. The deficient ..cap alpha..-chain synthesis caused these mice to exhibit an ..cap alpha..-thalassemia similar to human ..cap alpha..-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with ..cap alpha..-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining ..beta..-chain structure) produced twice as much SEC as 101 ..beta..-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC ..beta..-chain gene.

Hemoglobin of mice with radiation-induced mutations at the hemoglobin loci

International Nuclear Information System (INIS)

Popp, R.A.; Stratton, L.P.; Hawley, D.K.; Effron, K.

1979-01-01

Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F 1 offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of α-chains normally found in all SEC mice. The deficient α-chain synthesis caused these mice to exhibit an α-thalassemia similar to human α-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with α-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining β-chain structure) produced twice as much SEC as 101 β-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's in its unirradiated 101 mother and loss of chromosome 7 from the gamete of its irradiated SEC father did not express the SEC β-chain gene. (author)

Effect of Multiple Mutations in the Hemoglobin- and Hemoglobin-Haptoglobin-Binding Proteins, HgpA, HgpB, and HgpC, of Haemophilus influenzae Type b

OpenAIRE

Morton, Daniel J.; Whitby, Paul W.; Jin, Hongfan; Ren, Zhen; Stull, Terrence L.

1999-01-01

Haemophilus influenzae requires heme for growth and can utilize hemoglobin and hemoglobin-haptoglobin as heme sources. We previously identified two hemoglobin- and hemoglobin-haptoglobin-binding proteins, HgpA and HgpB, in H. influenzae HI689. Insertional mutation of hgpA and hgpB, either singly or together, did not abrogate the ability to utilize or bind either hemoglobin or the hemoglobin-haptoglobin complex. A hemoglobin affinity purification method was used to isolate a protein of approxi...

Importance of glycosylation on function of a potassium channel in neuroblastoma cells.

Directory of Open Access Journals (Sweden)

M K Hall

Full Text Available The Kv3.1 glycoprotein, a voltage-gated potassium channel, is expressed throughout the central nervous system. The role of N-glycans attached to the Kv3.1 glycoprotein on conducting and non-conducting functions of the Kv3.1 channel are quite limiting. Glycosylated (wild type, partially glycosylated (N220Q and N229Q, and unglycosylated (N220Q/N229Q Kv3.1 proteins were expressed and characterized in a cultured neuronal-derived cell model, B35 neuroblastoma cells. Western blots, whole cell current recordings, and wound healing assays were employed to provide evidence that the conducting and non-conducting properties of the Kv3.1 channel were modified by N-glycans of the Kv3.1 glycoprotein. Electrophoretic migration of the various Kv3.1 proteins treated with PNGase F and neuraminidase verified that the glycosylation sites were occupied and that the N-glycans could be sialylated, respectively. The unglycosylated channel favored a different whole cell current pattern than the glycoform. Further the outward ionic currents of the unglycosylated channel had slower activation and deactivation rates than those of the glycosylated Kv3.1 channel. These kinetic parameters of the partially glycosylated Kv3.1 channels were also slowed. B35 cells expressing glycosylated Kv3.1 protein migrated faster than those expressing partially glycosylated and much faster than those expressing the unglycosylated Kv3.1 protein. These results have demonstrated that N-glycans of the Kv3.1 glycoprotein enhance outward ionic current kinetics, and neuronal migration. It is speculated that physiological changes which lead to a reduction in N-glycan attachment to proteins will alter the functions of the Kv3.1 channel.

Biological role of site-specific O-glycosylation in cell adhesion activity and phosphorylation of osteopontin.

Science.gov (United States)

Oyama, Midori; Kariya, Yoshinobu; Kariya, Yukiko; Matsumoto, Kana; Kanno, Mayumi; Yamaguchi, Yoshiki; Hashimoto, Yasuhiro

2018-05-09

Osteopontin (OPN) is an extracellular glycosylated phosphoprotein that promotes cell adhesion by interacting with several integrin receptors. We previously reported that an OPN mutant lacking five O-glycosylation sites (Thr 134 /Thr 138 /Thr 143 /Thr 147 /Thr 152 ) in the threonine/proline-rich region increased cell adhesion activity and phosphorylation compared with the wild type. However, the role of O-glycosylation in cell adhesion activity and phosphorylation of OPN remains to be clarified. Here, we show that site-specific O-glycosylation in the threonine/proline-rich region of OPN affects its cell adhesion activity and phosphorylation independently and/or synergistically. Using site-directed mutagenesis, we found that OPN mutants with substitution sets of Thr 134 /Thr 138 or Thr 143 /Thr 147 /Thr 152 had decreased and increased cell adhesion activity, respectively. In contrast, the introduction of a single mutation into the O-glycosylation sites had no effect on OPN cell adhesion activity. An adhesion assay using function-blocking antibodies against αvβ3 and β1 integrins, as well as αvβ3 integrin-overexpressing A549 cells, revealed that site-specific O-glycosylation affected the association of OPN with the two integrins. Phosphorylation analyses using phos-tag and LC-MS/MS indicated that phosphorylation levels and sites were influenced by the O-glycosylation status, although the number of O-glycosylation sites was not correlated with the phosphorylation level in OPN. Furthermore, a correlation analysis between phosphorylation level and cell adhesion activity in OPN mutants with the site-specific O-glycosylation showed that they were not always correlated. These results provide conclusive evidence of a novel regulatory mechanism of cell adhesion activity and phosphorylation of OPN by site-specific O-glycosylation. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Moessbauer study of hemoglobin of diabetes

International Nuclear Information System (INIS)

Li Aiguo; Ni Xinbo; Cai Yingwen; Zhang Guilin; Zhang Hongde; Ge Yongxin

2000-01-01

The hemoglobins from normal adults (Gly-Hb 5%), people infected with diabetes (Gly-Hb 10%) and serious diabetics (Gly-Hb 15%) were investigated by Moessbauer spectroscopy at liquid nitrogen temperature. All the experimental spectra of hemoglobin are composed of three doublets corresponding to oxy-hemoglobin (Oxy-Hb), deoxy-hemoglobin (Deoxy-Hb) and low-spin hemo-chrome (Ls-Hemo) respectively. It is found that Oxy-Hb is decreasing but Deoxy-hb increasing for diabetes. Experimental results also indicate that the line-width of Moessbauer spectra of Oxy-Hb for diabetics is narrower than that for normal adults, showing that while Fe on Oxy-Hb exists in pile-up of some similar states for normal adults, but it becomes in single state for serious diabetes

Two-photon excited fluorescence emission from hemoglobin

Science.gov (United States)

Sun, Qiqi; Zeng, Yan; Zhang, Wei; Zheng, Wei; Luo, Yi; Qu, Jianan Y.

2015-03-01

Hemoglobin, one of the most important proteins in blood, is responsible for oxygen transportation in almost all vertebrates. Recently, we discovered two-photon excited hemoglobin fluorescence and achieved label-free microvascular imaging based on the hemoglobin fluorescence. However, the mechanism of its fluorescence emission still remains unknown. In this work, we studied the two-photon excited fluorescence properties of the hemoglobin subunits, heme/hemin (iron (II)/(III) protoporphyrin IX) and globin. We first studied the properties of heme and the similar spectral and temporal characteristics of heme and hemoglobin fluorescence provide strong evidence that heme is the fluorophore in hemoglobin. Then we studied the fluorescence properties of hemin, globin and methemoglobin, and found that the hemin may have the main effect on the methemoglobin fluorescence and that globin has tryptophan fluorescence like other proteins. Finally, since heme is a centrosymmetric molecule, that the Soret band fluorescence of heme and hemoglobin was not observed in the single photon process in the previous study may be due to the parity selection rule. The discovery of heme two-photon excited fluorescence may open a new window for heme biology research, since heme as a cofactor of hemoprotein has many functions, including chemical catalysis, electron transfer and diatomic gases transportation.

Convergent evolution of hemoglobin switching in jawed and jawless vertebrates.

Science.gov (United States)

Rohlfing, Kim; Stuhlmann, Friederike; Docker, Margaret F; Burmester, Thorsten

2016-02-01

During development, humans and other jawed vertebrates (Gnathostomata) express distinct hemoglobin genes, resulting in different hemoglobin tetramers. Embryonic and fetal hemoglobin have higher oxygen affinities than the adult hemoglobin, sustaining the oxygen demand of the developing organism. Little is known about the expression of hemoglobins during development of jawless vertebrates (Agnatha). We identified three hemoglobin switches in the life cycle of the sea lamprey. Three hemoglobin genes are specifically expressed in the embryo, four genes in the filter feeding larva (ammocoete), and nine genes correspond to the adult hemoglobin chains. During the development from the parasitic to the reproductive adult, the composition of hemoglobin changes again, with a massive increase of chain aHb1. A single hemoglobin chain is expressed constitutively in all stages. We further showed the differential expression of other globin genes: Myoglobin 1 is most highly expressed in the reproductive adult, myoglobin 2 expression peaks in the larva. Globin X1 is restricted to the embryo; globin X2 was only found in the reproductive adult. Cytoglobin is expressed at low levels throughout the life cycle. Because the hemoglobins of jawed and jawless vertebrates evolved independently from a common globin ancestor, hemoglobin switching must also have evolved convergently in these taxa. Notably, the ontogeny of sea lamprey hemoglobins essentially recapitulates their phylogeny, with the embryonic hemoglobins emerging first, followed by the evolution of larval and adult hemoglobins.

Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: focus on insulin glulisine

Directory of Open Access Journals (Sweden)

Heather Ulrich

2007-07-01

lispro or RHI in type 1 or 2 DM and it has been shown to be as safe and effective when used in a continuous subcutaneous insulin infusion (CSII. In summary, insulin glulisine is a safe, effective, and well tolerated rapid-acting insulin analogue across all BMIs and a worthy option for prandial glucose control in type 1 or 2 DM.Keywords: glycemic control, glycosylated hemoglobin A1c (HbA1c, rapid-acting insulin analogues, type 1 diabetes mellitus, type 2 diabetes mellitus, insulin glulisine, body mass index (BMI

Bone marrow derived stem cell therapy for type 2 diabetes mellitus.

Science.gov (United States)

Wehbe, Tarek; Chahine, Nassim Abi; Sissi, Salam; Abou-Joaude, Isabelle; Chalhoub, Louis

2016-01-01

In this study, 6 patients with type 2 diabetes (T2D) underwent autologous bone marrow mononuclear stem cell (BM-MNSC) infusion into the celiac and superior mesenteric arteries without pretreatment with any myeloablative or immune-suppressive therapy. Five of 6 (83%) showed normalization of their fasting glucose and the glycosylated hemoglobin (HbA1C) with significant reduction of their medication requirements. The HbA1C dropped on average 2.2 points. The three patients with diabetic complications showed improvement or stabilization and most patients reported improved energy and stamina. The durations of response varied between 6 months and 2 years. No patients had any significant adverse effects.

Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions.

Science.gov (United States)

Park, Yongho; Harper, Kaid C; Kuhl, Nadine; Kwan, Eugene E; Liu, Richard Y; Jacobsen, Eric N

2017-01-13

Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction. Copyright © 2017, American Association for the Advancement of Science.

Plasma Volume Expansion Resulting from Intravenous Glucose Tolerance Test

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Robert G. Hahn

2011-01-01

Full Text Available Objective. To quantify the degree of plasma volume expansion that occurs during an intravenous glucose tolerance test (IVGTT. Methods. Twenty healthy volunteers (mean age, 28 years underwent IVGTTs in which 0.3 g/kg of glucose 30% was injected as a bolus over 1 min. Twelve blood samples were collected over 75 min. The plasma glucose and blood hemoglobin concentrations were used to calculate the volume distribution (Vd and the clearance (CL of both the exogenous glucose and the injected fluid volume. Results. The IVGTT caused a virtually instant plasma volume expansion of 10%. The half-life of the glucose averaged 15 min and the plasma volume expansion 16 min. Correction of the fluid kinetic model for osmotic effects after injection reduced CL for the infused volume by 85%, which illustrates the strength of osmosis in allocating fluid back to the intracellular fluid space. Simulations indicated that plasma volume expansion can be reduced to 60% by increasing the injection time from 1 to 5 min and reducing the glucose load from 0.3 to 0.2 g/kg. Conclusion. A regular IVGTT induced an acute plasma volume expansion that peaked at 10% despite the fact that only 50–80 mL of fluid were administered.

O-GLYCOBASE version 4.0: a revised database of O-glycosylated proteins

DEFF Research Database (Denmark)

Gupta, Ramneek; Birch, Hanne; Rapacki, Krzysztof

1999-01-01

O-GLYCBASE is a database of glycoproteins with O-linked glycosylation sites. Entries with at least one experimentally verified O-glycosylation site have been complied from protein sequence databases and literature. Each entry contains information about the glycan involved, the species, sequence, ...

SEM visualization of glycosylated surface molecules using lectin-coated microspheres

Science.gov (United States)

Duke, J.; Janer, L.; Campbell, M.

1985-01-01

There are several techniques currently used to localize glycosylated surface molecules by scanning electron microscopy (Grinnell, 1980; Molday, 1976; Linthicum and Sell, 1975; Nicolson, 1974; Lo Buglio, et al, 1972). A simple and rapid method, using a modification of Grinnell's technique is reported here. Essentially, microspheres coated with Concavalin A are used to bind to glycosylated regions of the palatal shelf epithelium and are visualized in the scanning electron microscope (SEM).

Glycosylation of KSHV Encoded vGPCR Functions in Its Signaling and Tumorigenicity

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Hui Wu

2015-03-01

Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV is a tumor virus and the etiologic agent of Kaposi’s Sarcoma (KS. KSHV G protein-coupled receptor (vGPCR is an oncogene that is implicated in malignancies associated with KHSV infection. In this study, we show that vGPCR undergoes extensive N-linked glycosylation within the extracellular domains, specifically asparagines 18, 22, 31 and 202. An immunofluorescence assay demonstrates that N-linked glycosylation are necessary for vGPCR trafficking to the cellular membrane. Employing vGPCR mutants whose glycosylation sites were ablated, we show that these vGPCR mutants failed to activate downstream signaling in cultured cells and were severely impaired to induce tumor formation in the xenograph nude mouse model. These findings support the conclusion that glycosylation is critical for vGPCR tumorigenesis and imply that chemokine regulation at the plasma membrane is crucial for vGPCR mediated signaling.

O-GLYCBASE: a revised database of O-glycosylated proteins

DEFF Research Database (Denmark)

Hansen, Jan; Lund, Ole; Nielsen, Jens O.

1996-01-01

O-GLYCBASE is a comprehensive database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the SWISS-PROT and PIR databases as well as directly from recently published reports. Nineteen percent of the entries extracted from the databases n...... of mucin type O-glycosylation sites in mammalian glycoproteins exclusively from the primary sequence is made available by E-mail or WWW. The O-GLYCBASE database is also available electronically through our WWW server or by anonymous FTP....

Impact determination of strength and resistance training on Glycoside hemoglobin and blood sugar on patients with type II diabetes”

OpenAIRE

Bahman Hasanvand; Kobra Karami; Abdollah Khodadi; Mehdi Valipour

2011-01-01

Background : This study determined the impact of strength and resistance training on hemoglobin Glycoside and glucose in type II diabetic patients in Khorramabad in 2009. Materials and Methods: This quasi-experimental study was carried out on 30 men with type 2 diabetes referred to laboratories in Khorramabad, selected by screening and interview and purposeful sampling . After the subjects completed questionnaires of medical records and written consent, they were randomly divided into th...

O-GLYCBASE version 3.0: a revised database of O-glycosylated proteins

DEFF Research Database (Denmark)

Hansen, Jan; Lund, Ole; Nilsson, Jette

1998-01-01

O-GLYCBASE is a revised database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the literature, and from the sequence databases. Entries include informations about species, sequence, glycosylation sites and glycan type and is fully cr...

Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency

DEFF Research Database (Denmark)

Van Scherpenzeel, Monique; Timal, Sharita; Rymen, Daisy

2014-01-01

Congenital disorders of glycosylation comprise a group of genetic defects with a high frequency of intellectual disability, caused by deficient glycosylation of proteins and lipids. The molecular basis of the majority of the congenital disorders of glycosylation type I subtypes, localized...... in the cytosol and endoplasmic reticulum, has been solved. However, elucidation of causative genes for defective Golgi glycosylation (congenital disorders of glycosylation type II) remains challenging because of a lack of sufficiently specific diagnostic serum methods. In a single patient with intellectual...... disability, whole-exome sequencing revealed MAN1B1 as congenital disorder of glycosylation type II candidate gene. A novel mass spectrometry method was applied for high-resolution glycoprofiling of intact plasma transferrin. A highly characteristic glycosylation signature was observed with hybrid type N...

Carbohydrates on Proteins: Site-Specific Glycosylation Analysis by Mass Spectrometry

Science.gov (United States)

Zhu, Zhikai; Desaire, Heather

2015-07-01

Glycosylation on proteins adds complexity and versatility to these biologically vital macromolecules. To unveil the structure-function relationship of glycoproteins, glycopeptide-centric analysis using mass spectrometry (MS) has become a method of choice because the glycan is preserved on the glycosylation site and site-specific glycosylation profiles of proteins can be readily determined. However, glycopeptide analysis is still challenging given that glycopeptides are usually low in abundance and relatively difficult to detect and the resulting data require expertise to analyze. Viewing the urgent need to address these challenges, emerging methods and techniques are being developed with the goal of analyzing glycopeptides in a sensitive, comprehensive, and high-throughput manner. In this review, we discuss recent advances in glycoprotein and glycopeptide analysis, with topics covering sample preparation, analytical separation, MS and tandem MS techniques, as well as data interpretation and automation.

Osteoblasts extracellular matrix induces vessel like structures through glycosylated collagen I

Energy Technology Data Exchange (ETDEWEB)

Palmieri, D. [Genetics, DIBIO, University of Genova, Corso Europa 26, 16132 Genova (Italy); Valli, M.; Viglio, S. [Department of Biochemistry, University of Pavia (Italy); Ferrari, N. [Istituto Nazionale per la ricerca sul Cancro, Genova (Italy); Ledda, B.; Volta, C. [Genetics, DIBIO, University of Genova, Corso Europa 26, 16132 Genova (Italy); Manduca, P., E-mail: man-via@unige.it [Genetics, DIBIO, University of Genova, Corso Europa 26, 16132 Genova (Italy)

2010-03-10

Extracellular matrix (ECM) plays a fundamental role in angiogenesis affecting endothelial cells proliferation, migration and differentiation. Vessels-like network formation in vitro is a reliable test to study the inductive effects of ECM on angiogenesis. Here we utilized matrix deposed by osteoblasts as substrate where the molecular and structural complexity of the endogenous ECM is preserved, to test if it induces vessel-like network formation by endothelial cells in vitro. ECM is more similar to the physiological substrate in vivo than other substrates previously utilized for these studies in vitro. Osteogenic ECM, prepared in vitro from mature osteoblasts at the phase of maximal deposition and glycosylation of collagen I, induces EAhy926, HUVEC, and HDMEC endothelial cells to form vessels-like structures and promotes the activation of metalloproteinase-2 (MMP-2); the functionality of the p-38/MAPK signaling pathway is required. Osteogenic ECM also induces a transient increase of CXCL12 and a decrease of the receptor CXCR4. The induction of vessel-like networks is dependent from proper glycosylation of collagens and does not occur on osteogenic ECMs if deglycosylated by -galactosidase or on less glycosylated ECMs derived from preosteoblasts and normal fibroblasts, while is sustained on ECM from osteogenesis imperfecta fibroblasts only when their mutation is associated with over-glycosylation of collagen type I. These data support that post-translational glycosylation has a role in the induction in endothelial cells in vitro of molecules conductive to self-organization in vessels-like structures.

Osteoblasts extracellular matrix induces vessel like structures through glycosylated collagen I

International Nuclear Information System (INIS)

Palmieri, D.; Valli, M.; Viglio, S.; Ferrari, N.; Ledda, B.; Volta, C.; Manduca, P.

2010-01-01

Extracellular matrix (ECM) plays a fundamental role in angiogenesis affecting endothelial cells proliferation, migration and differentiation. Vessels-like network formation in vitro is a reliable test to study the inductive effects of ECM on angiogenesis. Here we utilized matrix deposed by osteoblasts as substrate where the molecular and structural complexity of the endogenous ECM is preserved, to test if it induces vessel-like network formation by endothelial cells in vitro. ECM is more similar to the physiological substrate in vivo than other substrates previously utilized for these studies in vitro. Osteogenic ECM, prepared in vitro from mature osteoblasts at the phase of maximal deposition and glycosylation of collagen I, induces EAhy926, HUVEC, and HDMEC endothelial cells to form vessels-like structures and promotes the activation of metalloproteinase-2 (MMP-2); the functionality of the p-38/MAPK signaling pathway is required. Osteogenic ECM also induces a transient increase of CXCL12 and a decrease of the receptor CXCR4. The induction of vessel-like networks is dependent from proper glycosylation of collagens and does not occur on osteogenic ECMs if deglycosylated by -galactosidase or on less glycosylated ECMs derived from preosteoblasts and normal fibroblasts, while is sustained on ECM from osteogenesis imperfecta fibroblasts only when their mutation is associated with over-glycosylation of collagen type I. These data support that post-translational glycosylation has a role in the induction in endothelial cells in vitro of molecules conductive to self-organization in vessels-like structures.

Small angle X-ray scattering on concentrated hemoglobin solutions

International Nuclear Information System (INIS)

Zinke, M.; Damaschun, G.; Mueller, J.J.; Ruckpaul, K.

1978-01-01

The small-angle X-ray scattering technique was used to determine the intermolecular structure and interaction potentials in oxi-and deoxi-hemoglobin solutions. The pair correlation function obtained by the ZERNICKE-PRINS equation characterizes the intermolecular structure of the hemoglobin molecules. The intermolecular structure is concentration dependent. The hemoglobin molecules have a 'short range order structure' with a range of about 4 molecule diameters at 324 g/l. The potential functions of the hemoglobin-hemoglobin interaction have been determined on the basis of fluid theories. Except for the deoxi-hemoglobin solution having the concentration 370 g/l, the pair interaction consists in a short repulsion and a weak short-range attraction against kT. The potential minimum is between 1.2 - 1.5 nm above the greatest hemoglobin diameter. (author)

Spectroscopic study of gamma irradiated bovine hemoglobin

International Nuclear Information System (INIS)

Maghraby, Ahmed Mohamed; Ali, Maha Anwar

2007-01-01

In the present study, the effects of ionizing radiation of Cs-137 and Co-60 from 4.95 to 743.14 Gy and from 40 Gy to 300 kGy, respectively, on some bovine hemoglobin characteristics were studied. Such an effect was evaluated using electron paramagnetic resonance (EPR) spectroscopy, and infra-red (IR) spectroscopy. Bovine hemoglobin EPR spectra were recorded and analyzed before and after irradiation and changes were explained in detail. IR spectra of unirradiated and irradiated Bovine hemoglobin were recorded and analyzed also. It was found that ionizing radiation may lead to the increase of free radicals production, the decrease in α-helices contents, which reflects the degradation of hemoglobin molecular structure, or at least its incomplete performance. Results also show that the combined application of EPR and FTIR spectroscopy is a powerful tool for determining structural modification of bovine hemoglobin samples exposed to gamma irradiation

Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural prey Veng, Cambodia.

Science.gov (United States)

Karakochuk, Crystal D; Whitfield, Kyly C; Barr, Susan I; Lamers, Yvonne; Devlin, Angela M; Vercauteren, Suzanne M; Kroeun, Hou; Talukder, Aminuzzaman; McLean, Judy; Green, Timothy J

2015-01-01

Anemia is common in Cambodian women. Potential causes include micronutrient deficiencies, genetic hemoglobin disorders, inflammation, and disease. We aimed to investigate factors associated with anemia (low hemoglobin concentration) in rural Cambodian women (18-45 y) and to investigate the relations between hemoglobin disorders and other iron biomarkers. Blood samples were obtained from 450 women. A complete blood count was conducted, and serum and plasma were analyzed for ferritin, soluble transferrin receptor (sTfR), folate, vitamin B-12, retinol binding protein (RBP), C-reactive protein (CRP), and α1 acid glycoprotein (AGP). Hemoglobin electrophoresis and multiplex polymerase chain reaction were used to determine the prevalence and type of genetic hemoglobin disorders. Overall, 54% of women had a genetic hemoglobin disorder, which included 25 different genotypes (most commonly, hemoglobin E variants and α(3.7)-thalassemia). Of the 420 nonpregnant women, 29.5% had anemia (hemoglobin 8.3 mg/L), hemoglobin disorders, respectively. There was no biochemical evidence of vitamin A deficiency (RBP 5 mg/L) and 26% (AGP >1 g/L) of nonpregnant women, respectively. By using an adjusted linear regression model, the strongest predictors of hemoglobin concentration were hemoglobin E homozygous disorder and pregnancy status. Other predictors were 2 other heterozygous traits (hemoglobin E and Constant Spring), parity, RBP, log ferritin, and vitamin B-12. Multiple biomarkers for anemia and iron deficiency were significantly influenced by the presence of hemoglobin disorders, hence reducing their diagnostic sensitivity. Further investigation of the unexpectedly low prevalence of IDA in Cambodian women is warranted. © 2015 American Society for Nutrition.

Metabolic control in patients with type 2 diabetes mellitus in a public hospital in Peru: a cross-sectional study in a low-middle income country

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Irma Elizabeth Huayanay-Espinoza

2016-10-01

Full Text Available Objective The objective of this study was to assess patients’ achievement of ADA (American Diabetes Association guideline recommendations for glycosylated hemoglobin, lipid profile, and blood pressure in a type 2 diabetes mellitus (T2DM outpatient clinic in a low-middle income country (LMIC setting. Methods This is a descriptive cross-sectional study with 123 ambulatory T2DM patients who are being treated at a public hospital in Lima, Peru. Data was gathered via standardized interviews, clinical surveys, and anthropomorphic measurements for each patient. Blood samples were drawn in fasting state for measures of glucose, glycosylated hemoglobin (HbA1c, and lipid profile. Laboratory parameters and blood pressure were evaluated according to ADA recommendations. Results Of the 123 patients, 81 were women and the mean age was 61.8 years. Glycemic control was abnormal in 82 (68.33% participants, and 45 (37.50% were unable to control their blood pressure. Lipid profile was abnormal in 73 (60.83% participants. Only nine (7.50% participants fulfilled ADA recommendations for glycemic, blood pressure, and lipid control. Conclusions Amongst individuals with type 2 diabetes, there was poor attainment of the ADA recommendations (HbA1c, blood pressure and LDL-cholesterol for ambulatory T2DM patients. Interventions are urgently needed in order to prevent long-term diabetic complications.

Glucose-tolerant β-glucosidase retrieved from the metagenome

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Taku eUchiyama

2015-06-01

Full Text Available β-glucosidases (BGLs hydrolyze cellooligosaccharides to glucose and play a crucial role in the enzymatic saccharification of cellulosic biomass. Despite their significance for the production of glucose, most identified BGLs are commonly inhibited by low (~mM concentrations of glucose. Therefore, BGLs that are insensitive to glucose inhibition have great biotechnological merit. We applied a metagenomic approach to screen for such rare glucose-tolerant BGLs. A metagenomic library was created in Escherichia coli (approximately 10,000 colonies and grown on LB agar plates containing 5-bromo-4-chloro-3-indolyl-β-D-glucoside, yielding 828 positive (blue colonies. These were then arrayed in 96-well plates, grown in LB, and secondarily screened for activity in the presence of 10% (w/v glucose. Seven glucose-tolerant clones were identified, each of which contained a single bgl gene. The genes were classified into two groups, differing by two nucleotides. The deduced amino acid sequences of these genes were identical (452 aa and found to belong to the glycosyl hydrolase family 1. The recombinant protein (Ks5A7 was overproduced in E. coli as a C-terminal 6 × His-tagged protein and purified to apparent homogeneity. The molecular mass of the purified Ks5A7 was determined to be 54 kDa by SDS-PAGE, and 160 kDa by gel filtration analysis. The enzyme was optimally active at 45°C and pH 5.0–6.5 and retained full or 1.5–2-fold enhanced activity in the presence of 0.1–0.5 M glucose. It had a low KM (78 µM with p-nitrophenyl β-D-glucoside; 0.36 mM with cellobiose and high Vmax (91 µmol min-1 mg-1 with p-nitrophenyl β-D-glucoside; 155 µmol min-1 mg-1 with cellobiose among known glucose-tolerant BGLs and was free from substrate (0.1 M cellobiose inhibition. The efficient use of Ks5A7 in conjunction with Trichoderma reesei cellulases in enzymatic saccharification of alkaline-treated rice straw was demonstrated by increased production of glucose.

Involvement of Aberrant Glycosylation in Thyroid Cancer

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Eiji Miyoshi

2010-01-01

Full Text Available Glycosylation is one of the most common posttranslational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharides structures are associated with many physiological and pathological events, including cell growth, migration and differentiation, and tumor invasion. Therefore, functional glycomics, which is a comprehensive study of the structures and functions of glycans, is attracting the increasing attention of scientists in various fields of life science. In cases of thyroid cancer, the biological characters and prognosis are completely different in each type of histopathology, and their oligosaccharide structures as well as the expression of glycosyltransferases are also different. In this review, we summarized our previous papers on oligosaccharides and thyroid cancers and discussed a possible function of oligosaccharides in the carcinogenesis in thyroid cancer.

Phenotypic variations in osmotic lysis of Sahel goat erythrocytes in non-ionic glucose media.

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Igbokwe, Nanacha Afifi; Igbokwe, Ikechukwu Onyebuchi

2016-03-01

Erythrocyte osmotic lysis in deionised glucose media is regulated by glucose influx, cation efflux, and changes in cell volume after water diffusion. Transmembrane fluxes may be affected by varied expression of glucose transporter protein and susceptibility of membrane proteins to glucose-induced glycosylation and oxidation in various physiologic states. Variations in haemolysis of Sahel goat erythrocytes after incubation in hyposmotic non-ionic glucose media, associated with sex, age, late pregnancy, and lactation, were investigated. The osmotic fragility curve in glucose media was sigmoidal with erythrocytes from goats in late pregnancy (PRE) or lactation (LAC) or from kid (KGT) or middle-aged (MGT) goats. Non-sigmoidal phenotype occurred in yearlings (YGT) and old (OGT) goats. The composite fragility phenotype for males and non-pregnant dry (NPD) females was non-sigmoidal. Erythrocytes with non-sigmoidal curves were more stable than those with sigmoidal curves because of inflectional shift of the curve to the left. Erythrocytes tended to be more fragile with male than female sex, KGT and MGT than YGT and OGT, and LAC and PRE than NPD. Thus, sex, age, pregnancy, and lactation affected the haemolytic pattern of goat erythrocytes in glucose media. The physiologic state of the goat affected the in vitro interaction of glucose with erythrocytes, causing variations in osmotic stability with variants of fragility phenotype. Variations in the effect of high extracellular glucose concentrations on the functions of membrane-associated glucose transporter, aquaporins, and the cation cotransporter were presumed to be relevant in regulating the physical properties of goat erythrocytes under osmotic stress.

Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

NARCIS (Netherlands)

Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood

NARCIS (Netherlands)

Maas, BHA; Buursma, A; Ernst, RAJ; Maas, AHJ; Zijlstra, WG

1998-01-01

We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O(2)Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that

Multidimensional fractionation is a requirement for quantitation of Golgi-resident glycosylation enzymes from cultured human cells.

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Lin, Chi-Hung; Chik, Jenny H L; Packer, Nicolle H; Molloy, Mark P

2015-02-06

Glycosylation results from the concerted action of glycosylation enzymes in the secretory pathway. In general, gene expression serves as the primary control mechanism, but post-translational fine-tuning of glycosylation enzyme functions is often necessary for efficient synthesis of specific glycan epitopes. While the field of glycomics has rapidly advanced, there lacks routine proteomic methods to measure expression of specific glycosylation enzymes needed to fill the gap between mRNA expression and the glycomic profile in a "reverse genomics" workflow. Toward developing this workflow we enriched Golgi membranes from two human colon cancer cell lines by sucrose density centrifugation and further mass-based fractionation by SDS-PAGE. We then applied mass spectrometry to demonstrate a doubling in the number of Golgi resident proteins identified, compared to the unenriched, low speed centrifuged supernatant of lysed cells. A total of 35 Golgi-resident glycosylation enzymes, of which 23 were glycosyltransferases, were identified making this the largest protein database so far of Golgi resident glycosylation enzymes experimentally identified in cultured human cells. We developed targeted mass spectrometry assays for specific quantitation of many of these glycosylation enzymes. Our results show that alterations in abundance of glycosylation enzymes at the protein level were generally consistent with the resultant glycomic profiles, but not necessarily with the corresponding glycosyltransferase mRNA expression as exemplified by the case of O-glycan core 1 T synthase.

N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting

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Erawan Borkham-Kamphorst

2018-04-01

Full Text Available Lipocalin 2 (LCN2 is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota. Human LCN2 contains one N-glycosylation site conserved in other species. It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion. We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3. Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles. Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding. In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.

Glucosamine derived DISAL donors for stereoselective glycosylations under neutral conditions

DEFF Research Database (Denmark)

Grathe, S.; Thygesen, M.B.; Larsen, K.

2005-01-01

DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report the synthe......DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report...... the synthesis of new glucosamine DISAL donors, carrying N-TCP, -Troc, or -TFAc protecting groups, and their use in beta-(1,2-trans) selective glycosylations, primarily in NMP in the absence of any added Lewis acids, or in CH3NO2 with LiClO4. Finally, precise microwave heating proved effective in promoting...

A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

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Tripathy, Devjit; Cobb, Jeff E; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C; Banerji, MaryAnn; Bray, George A; Buchanan, Thomas A; Clement, Stephen C; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Ratner, Robert E; Stentz, Frankie B; Reaven, Peter D; Musi, Nicolas; Ferrannini, Ele; DeFronzo, Ralph A

2015-05-01

The objective was to test the clinical utility of Quantose M(Q) to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose M(Q) is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13-0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose M(Q) increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min(-1)·kgwbm(-1)) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose M(Q) correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose M(Q) outperformed both Matsuda and fasting insulin in predicting incident diabetes. In IGT subjects, Quantose M(Q) parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose M(Q) may serve as a useful clinical test to identify and monitor therapy in insulin-resistant patients.

Improving interMediAte Risk management. MARK study

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Garcia-Gil Maria

2011-10-01

Full Text Available Abstract Background Cardiovascular risk functions fail to identify more than 50% of patients who develop cardiovascular disease. This is especially evident in the intermediate-risk patients in which clinical management becomes difficult. Our purpose is to analyze if ankle-brachial index (ABI, measures of arterial stiffness, postprandial glucose, glycosylated hemoglobin, self-measured blood pressure and presence of comorbidity are independently associated to incidence of vascular events and whether they can improve the predictive capacity of current risk equations in the intermediate-risk population. Methods/Design This project involves 3 groups belonging to REDIAPP (RETICS RD06/0018 from 3 Spanish regions. We will recruit a multicenter cohort of 2688 patients at intermediate risk (coronary risk between 5 and 15% or vascular death risk between 3-5% over 10 years and no history of atherosclerotic disease, selected at random. We will record socio-demographic data, information on diet, physical activity, comorbidity and intermittent claudication. We will measure ABI, pulse wave velocity and cardio ankle vascular index at rest and after a light intensity exercise. Blood pressure and anthropometric data will be also recorded. We will also quantify lipids, glucose and glycosylated hemoglobin in a fasting blood sample and postprandial capillary glucose. Eighteen months after the recruitment, patients will be followed up to determine the incidence of vascular events (later follow-ups are planned at 5 and 10 years. We will analyze whether the new proposed risk factors contribute to improve the risk functions based on classic risk factors. Discussion Primary prevention of cardiovascular diseases is a priority in public health policy of developed and developing countries. The fundamental strategy consists in identifying people in a high risk situation in which preventive measures are effective and efficient. Improvement of these predictions in our country

Study on the effects of Jinqi hypoglycemic table on serum P-sel, TNF-α and HbAlc levels in patients with type two diabetes mellitus

International Nuclear Information System (INIS)

Qi Falian; Xu Jun; Wang Bin; Chen Yingjian; Yin Qiuxia; Ke Bingshen

2007-01-01

Objective: To study the effects of Huang Qi and Huang Lian on serum P-selectin, tumor necrosis factor-α (TNF-α), glucose and glycosylated hemoglobin (HbAlc) levels in patients with type two diabetes mellitus (DM). Methods: Sixty DM2 patients were divided randomly into 2 equal numbered groups: one group were treated with routine hypoglycemic medicine, in other group, Jinqi hypoglycemic tablets were added besides western medicine. Fasting blood glucose, two hour postprandial glucose, HbAlc, P-SLT and TNF-α levels were measured detected before and after three months' treatment. Results: There were no significant differences between the plasma glucose, HbAlc, P-SLT and TNF-α levels (P>0.05) in the JinQi group and western medicine group before treatment. Fasting plasma glucose and postprandial glucose were decreased after treatment in both groups. HbAlc, P-SLT and TNF-α levels were significantly decreased after treatment (P<0.05, P<0.01, P<0.01) in JinQi group. Conclusion: On the basis of treatment with western medicine, additional Huang Lian and Huang Qi could further decrease HbAlc, P-SLT and TNF-α levels, stabilize blood glucose and provide better therapeutic results in patients with type 2 diabetes mellitus. (authors)

Diversity in protein glycosylation among insect species.

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Gianni Vandenborre

Full Text Available BACKGROUND: A very common protein modification in multicellular organisms is protein glycosylation or the addition of carbohydrate structures to the peptide backbone. Although the Class of the Insecta is the largest animal taxon on Earth, almost all information concerning glycosylation in insects is derived from studies with only one species, namely the fruit fly Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the differences in glycoproteomes between insects belonging to several economically important insect orders were studied. Using GNA (Galanthus nivalis agglutinin affinity chromatography, different sets of glycoproteins with mannosyl-containing glycan structures were purified from the flour beetle (Tribolium castaneum, the silkworm (Bombyx mori, the honeybee (Apis mellifera, the fruit fly (D. melanogaster and the pea aphid (Acyrthosiphon pisum. To identify and characterize the purified glycoproteins, LC-MS/MS analysis was performed. For all insect species, it was demonstrated that glycoproteins were related to a broad range of biological processes and molecular functions. Moreover, the majority of glycoproteins retained on the GNA column were unique to one particular insect species and only a few glycoproteins were present in the five different glycoprotein sets. Furthermore, these data support the hypothesis that insect glycoproteins can be decorated with mannosylated O-glycans. CONCLUSIONS/SIGNIFICANCE: The results presented here demonstrate that oligomannose N-glycosylation events are highly specific depending on the insect species. In addition, we also demonstrated that protein O-mannosylation in insect species may occur more frequently than currently believed.

Postoperative hemoglobin level in patients with femoral neck fracture.

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Nagra, Navraj S; Van Popta, Dmitri; Whiteside, Sigrid; Holt, Edward M

2016-01-01

The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture. Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored. There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative Day 5 Hb levels (pmeasurement, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p=0.046). The decrease in hemoglobin in the first 24-hour postoperative period (D0 to Day 1) is an underestimation of the ultimate lowest value in hemoglobin found at Day 2. Relying on the Day 1 hemoglobin level could be detrimental to patient care. We propose a method of predicting patients likely to be transfused and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring.

Transcription factor Nrf1 is topologically repartitioned across membranes to enable target gene transactivation through its acidic glucose-responsive domains.

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Zhang, Yiguo; Ren, Yonggang; Li, Shaojun; Hayes, John D

2014-01-01

The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap'n'collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Thus after Nrf1 is anchored within ER membranes, its acidic transactivation domains (TADs), including the Asn/Ser/Thr-rich (NST) glycodomain situated between acidic domain 1 (AD1) and AD2, are transiently translocated into the lumen of the ER, where NST is glycosylated in the presence of glucose to yield an inactive 120-kDa Nrf1 glycoprotein. Subsequently, portions of the TADs partially repartition across membranes into the cyto/nucleoplasmic compartments, whereupon an active 95-kDa form of Nrf1 accumulates, a process that is more obvious in glucose-deprived cells and may involve deglycosylation. The repartitioning of Nrf1 out of membranes is monitored within this protein by its acidic-hydrophobic amphipathic glucose-responsive domains, particularly the Neh5L subdomain within AD1. Therefore, the membrane-topological organization of Nrf1 dictates its post-translational modifications (i.e. glycosylation, the putative deglycosylation and selective proteolysis), which together control its ability to transactivate target genes.

Benfotiamine is similar to thiamine in correcting endothelial cell defects induced by high glucose.

Science.gov (United States)

Pomero, F; Molinar Min, A; La Selva, M; Allione, A; Molinatti, G M; Porta, M

2001-01-01

We investigated the hypothesis that benfotiamine, a lipophilic derivative of thiamine, affects replication delay and generation of advanced glycosylation end-products (AGE) in human umbilical vein endothelial cells cultured in the presence of high glucose. Cells were grown in physiological (5.6 mM) and high (28.0 mM) concentrations of D-glucose, with and without 150 microM thiamine or benfotiamine. Cell proliferation was measured by mitochondrial dehydrogenase activity. AGE generation after 20 days was assessed fluorimetrically. Cell replication was impaired by high glucose (72.3%+/-5.1% of that in physiological glucose, p=0.001). This was corrected by the addition of either thiamine (80.6%+/-2.4%, p=0.005) or benfotiamine (87.5%+/-8.9%, p=0.006), although it not was completely normalized (p=0.001 and p=0.008, respectively) to that in physiological glucose. Increased AGE production in high glucose (159.7%+/-38.9% of fluorescence in physiological glucose, p=0.003) was reduced by thiamine (113.2%+/-16.3%, p=0.008 vs. high glucose alone) or benfotiamine (135.6%+/-49.8%, p=0.03 vs. high glucose alone) to levels similar to those observed in physiological glucose. Benfotiamine, a derivative of thiamine with better bioavailability, corrects defective replication and increased AGE generation in endothelial cells cultured in high glucose, to a similar extent as thiamine. These effects may result from normalization of accelerated glycolysis and the consequent decrease in metabolites that are extremely active in generating nonenzymatic protein glycation. The potential role of thiamine administration in the prevention or treatment of vascular complications of diabetes deserves further investigation.

Garlic intake lowers fasting blood glucose: meta-analysis of randomized controlled trials.

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Hou, Li-qiong; Liu, Yun-hui; Zhang, Yi-yi

2015-01-01

Garlic is a common spicy flavouring agent also used for certain therapeutic purposes. Garlic's effects on blood glucose have been the subject of many clinical and animal studies, however, studies reporting hypoglycemic effects of garlic in humans are conflicting. A comprehensive literature search was conducted to identify relevant trials of garlic or garlic extracts on markers of glycemic control [fasting blood glucose (FBG), postprandial glucose (PPG), glycosylated haemoglobin (HbA1c)]. A meta-analysis of the effect of garlic intake on human was done to assess garlic's effectiveness in lowering glucose levels. Two reviewers extracted data from each of the identified studies. Seven eligible randomized controlled trials with 513 subjects were identified. Pooled analyses showed that garlic intake results in a statistically significant lowering in FBG [SMD=-1.67; 95% CI (-2.80, -0.55), p=0.004]. Our pooled analyses did not include PPG control and HbA1c outcomes. Because only 1 study included in the meta-analysis reported PPG variables and only 2 studies reported HbA1c variables. In conclusion, the current meta-analysis showed that the administration of garlic resulted in a significant reduction in FBG concentrations. More trials are needed to investigate the effectiveness of garlic on HbA1c and PPG.

Endoplasmic reticulum stress and N-glycosylation modulate expression of WFS1 protein

International Nuclear Information System (INIS)

Yamaguchi, Suguru; Ishihara, Hisamitsu; Tamura, Akira; Yamada, Takahiro; Takahashi, Rui; Takei, Daisuke; Katagiri, Hideki; Oka, Yoshitomo

2004-01-01

Mutations of the WFS1 gene are responsible for two hereditary diseases, Wolfram syndrome and low frequency sensorineural hearing loss. The WFS1 protein is a glycoprotein located in the endoplasmic reticulum (ER) membrane but its function is poorly understood. Herein we show WFS1 mRNA and protein levels in pancreatic islets to be increased with ER-stress inducers, thapsigargin and dithiothreitol. Another ER-stress inducer, the N-glycosylation inhibitor tunicamycin, also raised WFS1 mRNA but not protein levels. Site-directed mutagenesis showed both Asn-663 and Asn-748 to be N-glycosylated in mouse WFS1 protein. The glycosylation-defective WFS1 protein, in which Asn-663 and Asn-748 had been substituted with aspartate, exhibited an increased protein turnover rate. Consistent with this, the WFS1 protein was more rapidly degraded in the presence of tunicamycin. These data indicate that ER-stress and N-glycosylation play important roles in WFS1 expression and stability, and also suggest regulatory roles for this protein in ER-stress induced cell death

Hemoglobin levels in normal Filipino pregnant women.

Science.gov (United States)

Kuizon, M D; Natera, M G; Ancheta, L P; Platon, T P; Reyes, G D; Macapinlac, M P

1981-09-01

The hemoglobin concentrations during pregnancy in Filipinos belonging to the upper income group, who were prescribed 105 mg elemental iron daily, and who had acceptable levels of transferrin saturation, were examined in an attempt to define normal levels. The hemoglobin concentrations for each trimester followed a Gaussian distribution. The hemoglobin values equal to the mean minus one standard deviation were 11.4 gm/dl for the first trimester and 10.4 gm/dl for the second and third trimesters. Using these values as the lower limits of normal, in one group of pregnant women the prevalence of anemia during the last two trimesters was found lower than that obtained when WHO levels for normal were used. Groups of women with hemoglobin of 10.4 to 10.9 gm/dl (classified anemic by WHO criteria but normal in the present study) and those with 11.0 gm/dl and above could not be distinguished on the basis of their serum ferritin levels nor on the degree of decrease in their hemoglobin concentration during pregnancy. Many subjects in both groups, however, had serum ferritin levels less than 12 ng/ml which indicate poor iron stores. It might be desirable in future studies to determine the hemoglobin cut-off point that will delineate subjects who are both non-anemic and adequate in iron stores using serum ferritin levels as criterion for the latter.

IN VITRO STUDY ON INHIBITION OF GLYCOSYLATION OF ...

African Journals Online (AJOL)

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complications of diabetes mellitus (Makita et al., 1991). Apart from protein ... enzymes; inhibition of regulatory molecule binding; crosslinking of glycosylated .... further investigation specific bio active compound responsible for such activities.

Treatment with metformin and a dipeptidyl peptidase-4 inhibitor elevates apelin levels in patients with type 2 diabetes mellitus

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Fan YJ

2015-08-01

Full Text Available Yujuan Fan,* Yu Zhang,* Xuesong Li,* Hui Zheng, Yuping Song, Ning Zhang, Chunfang Shen, Xiaofang Fan, Fengdong Ren, Jiayi Shen, Guoguang Ren, Jialin Yang Department of Endocrinology, Central Hospital of Minhang District, Minhang Hospital affiliated to Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: The objective of this study was to assess the effects of metformin monotherapy or combined treatment with a dipeptidyl peptidase-4 inhibitor (vildagliptin on apelin levels in patients with type 2 diabetes mellitus. Methods: Twenty-five patients with poor glycemic control (glycosylated hemoglobin >6.5% [48 mmol/mol] taking 1,000 mg of metformin daily and 25 healthy controls matched for age and body mass index were enrolled in this study. Anthropometric parameters, glycemic and lipid profile, insulin resistance (homeostasis model assessment of insulin resistance index, and apelin levels were measured at baseline and at 12-week and 24-week visits. Results: At baseline, apelin levels were higher in the T2DM patients than in the controls (1.93±1.81 ng/mL versus 6.09±4.90 ng/mL; P<0.05. After 12 weeks, when vildagliptin was added, fasting blood glucose and glycosylated hemoglobin decreased, and apelin levels increased further (from 6.09±4.90 ng/mL to 24.23±12.59 ng/mL; P<0.05. Follow-up at 24 weeks showed no further improvement in the glycemic profile and no further increase in apelin levels. Conclusion: Both metformin and vildagliptin favorably changed glycemic indices and apelin levels. For patients inadequately controlled on a low dose of metformin, addition of vildagliptin may be helpful. Keywords: glucagon-like peptides, glucose-dependent insulinotropic polypeptide, antidiabetic drug, adipocytokine

Presence of metabolic syndrome in football linemen.

Science.gov (United States)

Buell, Jackie L; Calland, Doug; Hanks, Fiona; Johnston, Bruce; Pester, Benjamin; Sweeney, Robert; Thorne, Robert

2008-01-01

Metabolic syndrome is a clustering of symptoms associated with abdominal obesity that demonstrates a high risk for cardiovascular disease and type II diabetes mellitus. To evaluate football linemen in National Collegiate Athletic Association Divisions I, II, and III schools for the presence of metabolic syndrome according to the American Heart Association/National Heart, Lung, and Blood Institute criteria as well as to document other related biomarkers. Cross-sectional descriptive study. Three university locations on the first full day of football camp in early morning. Of 76 football linemen, 70 were able to provide blood samples. Height, mass, blood pressure, upper-body skinfolds, and waist circumference were measured at various stations. Two small venous samples of blood were collected and analyzed in a hospital laboratory for fasting insulin, glucose, high-density lipoprotein, total cholesterol, triglycerides, C-reactive protein, and glycosylated hemoglobin. The last station was a verbal family history for cardiovascular disease and diabetes; also, athletes filled out a nutrition attitudes questionnaire. Of the 70 athletes, 34 were identified as having metabolic syndrome according to measures of blood pressure, waist circumference, fasting glucose, high-density lipoprotein, and triglycerides. The mean total cholesterol-to-high-density lipoprotein cholesterol ratio for the group was 4.95, with 32 participants displaying values higher than 5.0. Twelve volunteers had total cholesterol levels greater than 200 mmol/L, 15 had high levels of C-reactive protein, and 9 had slightly elevated levels of glycosylated hemoglobin. Although athletes might be assumed to be protected from risks of cardiovascular disease, we found a high incidence of metabolic syndrome and other associated adverse biomarkers for heart disease in collegiate football linemen. Early screening, awareness, and intervention may have favorable effects on the overall health outcomes of football linemen.

Clinical Use of Continuous Glucose Monitoring in Adults with Type 1 Diabetes.

Science.gov (United States)

Slattery, David; Choudhary, Pratik

2017-05-01

With the emphasis on intensive management of type 1 diabetes, data from studies support frequent monitoring of glucose levels to improve glycemic control and reduce glucose variability, which can be related to an increase in macro and microvascular complications. However, few perform capillary blood glucose that frequently. There are currently two available alternatives that this review will discuss, continuous glucose monitoring (CGM) and flash glucose monitoring. CGM has become an important diagnostic and therapeutic option in optimizing diabetes management. CGM systems are now more accurate, smaller, and easier to use compared to original models. Randomized controlled trials (RCTs) have demonstrated that CGM can improve Hemoglobin A1c (HbA1C) and reduce glucose variability in both continuous subcutaneous insulin infusion and multiple daily injection users. When used in an automated "insulin-suspend" system, reduced frequency of hypoglycemia and shorter time spent in hypoglycemic range have been demonstrated. Despite the potential benefits CGM has to offer in clinical practice, concerns exist on the accuracy of these devices and patient compliance with therapy, which may prevent the true clinical benefit of CGM being achieved, as observed in RCTs. Flash glucose monitoring systems FreeStyle ® Libre™ (Abbott Diabetes Care, Alameda, CA) are as accurate as many CGM systems available and have the added benefit of being factory calibrated. Studies have shown that flash glucose monitoring systems are very well tolerated by patients and effectively reduce glucose variability, increasing time in range.

Relation of microalbuminuria to glycosylated hemoglobin and ...

African Journals Online (AJOL)

Background: Nephropathy is one of the complications of type 2 diabetes ... Materials and Methods: Study was conducted at Medical College, Kolkata. ... Results: Urinary microalbumin, HbA1c levels were significantly higher in the cases.

Relation of microalbuminuria to glycosylated hemoglobin and ...

African Journals Online (AJOL)

2012-04-22

Apr 22, 2012 ... between HbA1c and microalbuminuria with the duration of diabetes is not clear. ... the detection of increased urinary microalbumin levels at the initial stage can avert, ..... haemoglobin and Lipid Profile in Diabetic Retinopathy.

Hair cortisol concentration and glycated hemoglobin in African American adults.

Science.gov (United States)

Lehrer, H Matthew; Dubois, Susan K; Maslowsky, Julie; Laudenslager, Mark L; Steinhardt, Mary A

2016-10-01

African Americans have higher diabetes prevalence compared to Whites. They also have elevated cortisol levels - indicating possible HPA axis dysregulation - which may raise blood glucose as part of the biological response to physiological and psychosocial stress. Little is known about chronic cortisol levels in African Americans, and even less about the role of chronically elevated cortisol in type 2 diabetes development in this racial group. We used analysis of cortisol in hair to examine associations of long-term (∼3months) cortisol levels with glycated hemoglobin (HbA1c) in a group of African American adults. In exploratory analyses, we also studied the relationship of hair dehydroepiandrosterone (DHEA) with HbA1c. Participants were 61 community-dwelling African American adults (85% female; mean age 54.30 years). The first 3cm of scalp-near hair were analyzed for cortisol and DHEA concentration using enzyme-linked immunoassay analysis. Glycated hemoglobin was assessed, and regression analyses predicting HbA1c from hair cortisol and DHEA were performed in the full sample and in a subsample of participants (n=20) meeting the National Institute of Diabetes and Digestive Kidney Disease (NIDDK) criteria for type 2 diabetes (HbA1c≥6.5%). In the full sample, HbA1c increased with hair cortisol level (β=0.22, p=0.04, f(2)=0.10), independent of age, sex, chronic health conditions, diabetes medication use, exercise, and depressive symptoms. In the subsample of participants with an HbA1c≥6.5%, hair cortisol was also positively related to HbA1c (β=0.45, p=0.04, f(2)=0.32), independent of diabetes medication use. Glycated hemoglobin was unrelated to hair DHEA in both the full sample and HbA1c≥6.5% subsample. Long-term HPA axis dysregulation in the form of elevated hair cortisol is associated with elevated HbA1c in African American adults. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

International Nuclear Information System (INIS)

Jones, Meredith B.; Tomiya, Noboru; Betenbaugh, Michael J.; Krag, Sharon S.

2010-01-01

Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man 5 GlcNAc 2 -P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man 9 GlcNAc 2 -P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc 3 Man 9 GlcNAc 2 -P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man 5 GlcNAc 2 -PP-Dol through Glc 1 Man 9 GlcNAc 2 -PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc 3 Man 9 GlcNAc 2 -P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

Energy Technology Data Exchange (ETDEWEB)

Jones, Meredith B., E-mail: mbauman7@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Tomiya, Noboru, E-mail: ntomiya1@jhu.edu [Department of Biology, Johns Hopkins University, 3400 North Charles Street, Mudd Hall 104A, Baltimore, MD 21218 (United States); Betenbaugh, Michael J., E-mail: beten@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Krag, Sharon S., E-mail: skrag@jhsph.edu [Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205 (United States)

2010-04-23

Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man{sub 5}GlcNAc{sub 2}-P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man{sub 9}GlcNAc{sub 2}-P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man{sub 5}GlcNAc{sub 2}-PP-Dol through Glc{sub 1}Man{sub 9}GlcNAc{sub 2}-PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

Genome-scale metabolic model of Pichia pastoris with native and humanized glycosylation of recombinant proteins.

Science.gov (United States)

Irani, Zahra Azimzadeh; Kerkhoven, Eduard J; Shojaosadati, Seyed Abbas; Nielsen, Jens

2016-05-01

Pichia pastoris is used for commercial production of human therapeutic proteins, and genome-scale models of P. pastoris metabolism have been generated in the past to study the metabolism and associated protein production by this yeast. A major challenge with clinical usage of recombinant proteins produced by P. pastoris is the difference in N-glycosylation of proteins produced by humans and this yeast. However, through metabolic engineering, a P. pastoris strain capable of producing humanized N-glycosylated proteins was constructed. The current genome-scale models of P. pastoris do not address native nor humanized N-glycosylation, and we therefore developed ihGlycopastoris, an extension to the iLC915 model with both native and humanized N-glycosylation for recombinant protein production, but also an estimation of N-glycosylation of P. pastoris native proteins. This new model gives a better prediction of protein yield, demonstrates the effect of the different types of N-glycosylation of protein yield, and can be used to predict potential targets for strain improvement. The model represents a step towards a more complete description of protein production in P. pastoris, which is required for using these models to understand and optimize protein production processes. © 2015 Wiley Periodicals, Inc.

Congenital disorders of glycosylation: The Saudi experience.

Science.gov (United States)

Alsubhi, Sarah; Alhashem, Amal; Faqeih, Eissa; Alfadhel, Majid; Alfaifi, Abdullah; Altuwaijri, Waleed; Alsahli, Saud; Aldhalaan, Hesham; Alkuraya, Fowzan S; Hundallah, Khalid; Mahmoud, Adel; Alasmari, Ali; Mutairi, Fuad Al; Abduraouf, Hanem; AlRasheed, Layan; Alshahwan, Saad; Tabarki, Brahim

2017-10-01

We retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients, 11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients. © 2017 Wiley Periodicals, Inc.

Optimal Synthetic Glycosylation of a Therapeutic Antibody.

Science.gov (United States)

Parsons, Thomas B; Struwe, Weston B; Gault, Joseph; Yamamoto, Keisuke; Taylor, Thomas A; Raj, Ritu; Wals, Kim; Mohammed, Shabaz; Robinson, Carol V; Benesch, Justin L P; Davis, Benjamin G

2016-02-12

Glycosylation patterns in antibodies critically determine biological and physical properties but their precise control is a significant challenge in biology and biotechnology. We describe herein the optimization of an endoglycosidase-catalyzed glycosylation of the best-selling biotherapeutic Herceptin, an anti-HER2 antibody. Precise MS analysis of the intact four-chain Ab heteromultimer reveals nonspecific, non-enzymatic reactions (glycation), which are not detected under standard denaturing conditions. This competing reaction, which has hitherto been underestimated as a source of side products, can now be minimized. Optimization allowed access to the purest natural form of Herceptin to date (≥90 %). Moreover, through the use of a small library of sugars containing non-natural functional groups, Ab variants containing defined numbers of selectively addressable chemical tags (reaction handles at Sia C1) in specific positions (for attachment of cargo molecules or "glycorandomization") were readily generated.

Dengue Virus Glycosylation: What Do We Know?

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Sally S. L. Yap

2017-07-01

Full Text Available In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E and non-structural protein 1 (NS1 are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.

Lixisenatide as add-on therapy to basal insulin

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Brown DX

2013-12-01

Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

Non-invasive method to detect the changes of glucose concentration in whole blood using photometric technique.

Science.gov (United States)

Rajan, Shiny Amala Priya; Towe, Bruce C

2014-01-01

A non-invasive method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm, which is a peak absorbance of hemoglobin. As the glucose concentration in blood decreases, its osmolarity also decreases and the Red Blood Cells (RBCs) swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds.

Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth.

Science.gov (United States)

Tirabanchasak, Sirapassorn; Siripunthana, Sukumarn; Supornsilchai, Vichit; Wacharasindhu, Suttipong; Sahakitrungruang, Taninee

2015-09-01

Subjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described. We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT. We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose > 155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤ 155 mg/dL. Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of > 155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

Heterozygote Hemoglobin G-Coushatta as the Cause of a Falsely Decreased Hemoglobin A1C in an Ion-Exchange HPLC Method

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Kurtoğlu Ayşegül Uğur

2017-09-01

Full Text Available Glycated hemoglobin (HbA1c is used for the assessment of glycemic control in patients with diabetes. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA1c measurement. Here, we report two cases of Hemoglobin G-Coushatta (HBB:c.68A>C variant that interferes in the measurement of HbA1c by a cation-exchange HPLC (CE-HPLC method. HbA1c was measured by a CE-HPLC method in a Tosoh HLC-723 G7 instrument. The HbA1c levels were 2.9% and 4%. These results alerted us to a possible presence of hemoglobinopathy. In the hemoglobin variant analysis, HbA2 levels were detected as 78.3% and 40.7% by HPLC using the short program for the Biorad Variant II. HbA1c levels were measured by an immunoturbidimetric assay in a Siemens Dimension instrument. HbA1c levels were reported as 5.5% and 5.3%. DNA mutation analysis was performed to detect the abnormal hemoglobin variant. Presence of Hemoglobin G-Coushatta variant was detected in the patients. The Hb G-Coushatta variants have an impact on the determination of glycated hemoglobin levels using CEHPLC resulting in a false low value. Therefore, it is necessary to use another measurement method.

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot

DEFF Research Database (Denmark)

Bandara, Mithila D.; Yasomanee, Jagodige P.; Rath, Nigam P.

2017-01-01

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S......-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning...

A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

Science.gov (United States)

Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

2015-01-01

Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

Individualized anemia management reduces hemoglobin variability in hemodialysis patients.

Science.gov (United States)

Gaweda, Adam E; Aronoff, George R; Jacobs, Alfred A; Rai, Shesh N; Brier, Michael E

2014-01-01

One-size-fits-all protocol-based approaches to anemia management with erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of hemoglobin variability. In this single-center, double-blind, randomized controlled trial, we tested the hypothesis that individualized dosing of ESA improves hemoglobin variability over a standard population-based approach. We enrolled 62 hemodialysis patients and followed them over a 12-month period. Patients were randomly assigned to receive ESA doses guided by the Smart Anemia Manager algorithm (treatment) or by a standard protocol (control). Dose recommendations, performed on a monthly basis, were validated by an expert physician anemia manager. The primary outcome was the percentage of hemoglobin concentrations between 10 and 12 g/dl over the follow-up period. A total of 258 of 356 (72.5%) hemoglobin concentrations were between 10 and 12 g/dl in the treatment group, compared with 208 of 336 (61.9%) in the control group; 42 (11.8%) hemoglobin concentrations were hemoglobin concentrations were >12 g/dl in the treatment group compared with 46 (13.4%) in the control group. The median ESA dosage per patient was 2000 IU/wk in both groups. Five participants received 6 transfusions (21 U) in the treatment group, compared with 8 participants and 13 transfusions (31 U) in the control group. These results suggest that individualized ESA dosing decreases total hemoglobin variability compared with a population protocol-based approach. As hemoglobin levels are declining in hemodialysis patients, decreasing hemoglobin variability may help reduce the risk of transfusions in this population.

Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions

DEFF Research Database (Denmark)

Pedersen, Nis Borbye; Wang, Shengjun; Narimatsu, Yoshiki

2014-01-01

, which in wild-type CHO cells is glycosylated with the typical sialylated core 1 structure. The glycosites in linker regions of LDLR class A repeats are conserved in LDLR from man to Xenopus and found in other homologous receptors. O-Glycosylation is controlled by a large family of polypeptide Gal...

Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites

DEFF Research Database (Denmark)

Julenius, Karin; Mølgaard, Anne; Gupta, Ramneek

2005-01-01

could be predicted from averaged properties together with the fact that glycosylation sites are not precisely conserved indicates that mucin-type glycosylation in most cases is a bulk property and not a very site-specific one. NetOGlyc 3.1 is made available at www.cbs.dtu.dk/services/netoglyc....

Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

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Inês Gomes Ferreira

2018-02-01

Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

The interaction of 2,3-diphosphoglycerate with various human hemoglobins

Science.gov (United States)

Bunn, H. Franklin; Briehl, Robin W.

1970-01-01

Oxygen equilibria were measured on a number of human hemoglobins, which had been “stripped” of organic phosphates and isolated by column chromatography. In the presence of 2 × 10-4 M 2,3-diphosphoglycerate (2,3-DPG), the P50 of hemoglobins A, A2, S, and C increased about twofold, signifying a substantial and equal decrease in oxygen affinity. Furthermore, hemoglobins Chesapeake and MMilwaukee-1 which have intrinsically high and low oxygen affinities, respectively, also showed a twofold increase in P50 in the presence of 2 × 10-4 M 2,3-DPG. In comparison to these, hemoglobins AIC and F were less reactive with 2,3-DPG while hemoglobin FI showed virtually no reactivity. The N-terminal amino of each β-chain of hemoglobin AIC is linked to a hexose. In hemoglobin FI the N-terminal amino of each γ-chain is acetylated. These results suggest that the N-terminal amino groups of the non-α-chains are involved in the binding of 2,3-DPG to hemoglobin. PMID:5422014

Correlation between Body Mass Index and Insulin Levels in Premenopausal Women

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Anastasia Sachinidou

2017-12-01

Full Text Available Obesity is one of the most important problems of modern societies, and is considered a modern plague which tends to evolve to a global pandemic. Premenopausal women, most of the times, manifest hormonal dysfunctions and dysfunctions in their metabolism. The consequences are weight gain, heart diseases, hypertension and diabetes mellitus type 2. Purpose: The purpose of this study was to examine if vitamin D levels and Glycosylated hemoglobin are affected by exercise and if there is a connection between Body Mass Index (BMI and insulin. Method: The research involved 48 healthy premenopausal women who answered questionnaires which included questions about their height, weight, waist circumference, lifestyle and history of menstruation. This questionnaire, after due electronic approval, was based on a model of the German Sports and Research Centre (Karlsruhe Institut Fuer Sport und Sportwissenschaft. Women, after having completed a consent form, were also subjected to laboratory testing to determine their insulin, vitamin D levels and Glycosylated hemoglobin levels. To specify the vitamin D and insulin levels a method of direct chemiluminescence was used, and Glycosylated hemoglobin identification was specified using an automated light metering method. Statistical analysis performed using ΙΒΜ SPSS 22. Results: At the premenopausal women (41+/-7ετών (BMI24+/-4 kg/m2 a significant impact during the time of the exercises in the glycosylated hemoglobin (p = 0.038 0.05 regarding the levels of Glycosylated hemoglobin and the combination of exercise with other physical activities. Finally, a significant correlation between BMI and insulin (p=0.001<0.05 was detected. Furthermore, there was no statistically significant difference found in vitamin D levels relative to physical activity. Conclusion: During the research it was found that BMI influences the secretion of insulin, and insulin resistance that is a metabolism disorder, is a result of

A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism.

NARCIS (Netherlands)

Morava, E.; Wevers, R.A.; Cantagrel, V.; Hoefsloot, L.H.; Al-Gazali, L.; Schoots, J.; Rooij, A. van; Huijben, K.; Ravenswaaij-Arts, C.M.A. van; Jongmans, M.C.J.; Sykut-Cegielska, J.; Hoffmann, G.F.; Bluemel, P.; Adamowicz, M.; Reeuwijk, J. van; Ng, B.G.; Bergman, J.E.; Bokhoven, J.H.L.M. van; Korner, C.; Babovic-Vuksanovic, D.; Willemsen, M.A.A.P.; Gleeson, J.G.; Lehle, L.; Brouwer, A.P.M. de; Lefeber, D.J.

2010-01-01

Cerebellar hypoplasia and slowly progressive ophthalmological symptoms are common features in patients with congenital disorders of glycosylation type I. In a group of patients with congenital disorders of glycosylation type I with unknown aetiology, we have previously described a distinct phenotype

Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

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Chiaki Nagai-Okatani

Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

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Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

2017-07-01

The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

NetOglyc: prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility

DEFF Research Database (Denmark)

Hansen, Jan Erik; Lund, Ole; Tolstrup, Niels

1998-01-01

-glycosylated serine and threonine residues in independent test sets, thus proving more accurate than matrix statistics and vector projection methods. Predicition of O-glycosylation sites in the envelope glycoprotein gp120 from the primate lentiviruses HIV-1, HIV-2 and SIV are presented. The most conserved O...... structure and surface accessibility. The sequence context of glycosylated threonines was found to differ from that of serine, and the sites were found to cluster. Non-clustered sites had a sequence context different from that of clustered sites. charged residues were disfavoured at postition -1 and +3......-glycosylation signals in these evolutionary-related glycoproteins were found in their first hypervariable loop, V1. However, the strain variation for HIV-1 gp120 was significant. A computer server, available through WWW or E-mail, has been developed for prediction of mucin type O-glycosylation sites in proteins based...

Role of structure and glycosylation of adsorbed protein films in biolubrication.

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Deepak H Veeregowda

Full Text Available Water forms the basis of lubrication in the human body, but is unable to provide sufficient lubrication without additives. The importance of biolubrication becomes evident upon aging and disease, particularly under conditions that affect secretion or composition of body fluids. Insufficient biolubrication, may impede proper speech, mastication and swallowing, underlie excessive friction and wear of articulating cartilage surfaces in hips and knees, cause vaginal dryness, and result in dry, irritated eyes. Currently, our understanding of biolubrication is insufficient to design effective therapeutics to restore biolubrication. Aim of this study was to establish the role of structure and glycosylation of adsorbed protein films in biolubrication, taking the oral cavity as a model and making use of its dynamics with daily perturbations due to different glandular secretions, speech, drinking and eating, and tooth brushing. Using different surface analytical techniques (a quartz crystal microbalance with dissipation monitoring, colloidal probe atomic force microscopy, contact angle measurements and X-ray photo-electron spectroscopy, we demonstrated that adsorbed salivary conditioning films in vitro are more lubricious when their hydrophilicity and degree of glycosylation increase, meanwhile decreasing their structural softness. High-molecular-weight, glycosylated proteins adsorbing in loops and trains, are described as necessary scaffolds impeding removal of water during loading of articulating surfaces. Comparing in vitro and in vivo water contact angles measured intra-orally, these findings were extrapolated to the in vivo situation. Accordingly, lubricating properties of teeth, as perceived in 20 volunteers comprising of equal numbers of male and female subjects, could be related with structural softness and glycosylation of adsorbed protein films on tooth surfaces. Summarizing, biolubrication is due to a combination of structure and glycosylation

Porphyromonas endodontalis binds, reduces and grows on human hemoglobin.

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Zerr, M; Drake, D; Johnson, W; Cox, C D

2001-08-01

Porphyromonas endodontalis is a black-pigmented, obligate anaerobic rod-shaped bacterium implicated as playing a major role in endodontic infections. We have previously shown that P. endodontalis requires the porphyrin nucleus, preferably supplied as hemoglobin, as a growth supplement. The bacteria also actively transport free iron, although this activity does not support growth in the absence of a porphyrin source. The purpose of this study was to further investigate the binding and subsequent utilization of human hemoglobin by P. endodontalis. P. endodontalis binds hemoglobin and reduces the Fe(III) porphyrin, resulting in a steady accumulation of ferrous hemoglobin. Reduction of methemoglobin was similar to the extracellular reduction of nitrobluetetrazolium in the presence of oxidizable substrate. Turbidimetric and viable cell determinations showed that P. endodontalis grew when supplied only hemoglobin. Therefore, we conclude that hemoglobin appears to serve as a sole carbon and nitrogen source, and that these bacteria reduce extracellular compounds at the expense of oxidized substrates.

Post-transfusion hemoglobin values and patient blood management

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Moerman, Jan; Vermeulen, Edith; Van Mullem, Mia

2018-01-01

Objectives: The objective of this retrospective study was to evaluate the added value of communicating post-transfusion hemoglobin values to clinicians as a strategy to improve RBC utilization in a 500-bed hospital. Methods: The total number of RBC transfusions, the mean number of RBC units...... transfused per patient, the mean pre- and post-transfusion hemoglobin values, the ratio of patients transfused and the ratio of patients with a post-transfusion hemoglobin > 10.5 g/dL were calculated per service and per department for six months. The data were reported to each service and compared...... with the data of the department as peer group. The impact of this communication strategy was evaluated in the following six months. Results: In the six months pre-intervention, the mean post-transfusion hemoglobin value was 9.2 g/dL. Post-transfusion hemoglobin was > 10.5 g/dL in 13.4% of patients (112...

A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

International Nuclear Information System (INIS)

Kalra, Rajkumar S.; Wadhwa, Renu

2015-01-01

Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein

A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

Energy Technology Data Exchange (ETDEWEB)

Kalra, Rajkumar S., E-mail: renu-wadhwa@aist.go.jp; Wadhwa, Renu, E-mail: renu-wadhwa@aist.go.jp [Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science and Technology (AIST Central 4), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan)

2015-02-27

Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.

Microfluidic glycosyl hydrolase screening for biomass-to-biofuel conversion.

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Bharadwaj, Rajiv; Chen, Zhiwei; Datta, Supratim; Holmes, Bradley M; Sapra, Rajat; Simmons, Blake A; Adams, Paul D; Singh, Anup K

2010-11-15

The hydrolysis of biomass to fermentable sugars using glycosyl hydrolases such as cellulases and hemicellulases is a limiting and costly step in the conversion of biomass to biofuels. Enhancement in hydrolysis efficiency is necessary and requires improvement in both enzymes and processing strategies. Advances in both areas in turn strongly depend on the progress in developing high-throughput assays to rapidly and quantitatively screen a large number of enzymes and processing conditions. For example, the characterization of various cellodextrins and xylooligomers produced during the time course of saccharification is important in the design of suitable reactors, enzyme cocktail compositions, and biomass pretreatment schemes. We have developed a microfluidic-chip-based assay for rapid and precise characterization of glycans and xylans resulting from biomass hydrolysis. The technique enables multiplexed separation of soluble cellodextrins and xylose oligomers in around 1 min (10-fold faster than HPLC). The microfluidic device was used to elucidate the mode of action of Tm_Cel5A, a novel cellulase from hyperthermophile Thermotoga maritima . The results demonstrate that the cellulase is active at 80 °C and effectively hydrolyzes cellodextrins and ionic-liquid-pretreated switchgrass and Avicel to glucose, cellobiose, and cellotriose. The proposed microscale approach is ideal for quantitative large-scale screening of enzyme libraries for biomass hydrolysis, for development of energy feedstocks, and for polysaccharide sequencing.

Hemoglobin affinity in Andean rodents

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HRVOJ OSTOJIC

2002-01-01

Full Text Available Blood hemoglobin oxygen affinity (P50 was measured in three Andean species and in the laboratory rat (control, all raised near sea level. Chinchilla lanigera (Molina, 1792 has an altitudinal habitat range from low Andean slopes up to 3000 m., while Chinchilla brevicaudata (Waterhouse, 1848 has an altitudinal range from 3000 to 5000 m. The laboratory type guinea pig, wild type guinea pig (Cavia porcellus, (Waterhouse, 1748, and laboratory rat (Rattus norvegicus were also raised at sea level. The Andean species had high hemoglobin oxygen affinities (low P50 compared with the rat. Chinchilla brevicaudata had a higher affinity than Chinchilla lanigera. The wild type guinea pig had a higher affinity than the laboratory type. As has been shown in other species, this is another example of an inverse correlation between the altitude level and the P50 values. This is the first hemoglobin oxygen affinity study in Chinchilla brevicaudata.

Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

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Olga V Savinova

Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

Glycosylation analysis of recombinant neutral protease I from Aspergillus oryzae expressed in Pichia pastoris.

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Lei, Da; Xu, Yang; He, Qinghua; Pang, Yifeng; Chen, Bo; Xiong, Liang; Li, Yanping

2013-12-01

Neutral protease I from Aspergillus oryzae 3.042 was expressed in Pichia pastoris and its N-glycosylation properties were analyzed. After purification by nickel-affinity chromatography column, the recombinant neutral protease (rNPI) was confirmed to be N-glycosylated by periodicacid/Schiff's base staining and Endo H digestion. Moreover, the deglycosylated protein's molecular weight decreased to 43.3 kDa from 54.5 kDa analyzed by SDS-PAGE and MALDI-TOF-MS, and the hyperglycosylation extent was 21 %. The N-glycosylation site of rNPI was analyzed by nano LC-MS/MS after digesting by trypsin and Glu-C, and the unique potential site Asn41 of mature peptide was found to be glycosylated. Homology modeling of the 3D structure of rNPI indicated that the attached N-glycans hardly affected neutral protease's activity due to the great distance away from the active site of the enzyme.

The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome

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Younghak Lee

2017-09-01

Full Text Available BackgroundCushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined.MethodsA retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records.ResultsEosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome.ConclusionSmaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome.

The Eosinophil Count Tends to Be Negatively Associated with Levels of Serum Glucose in Patients with Adrenal Cushing Syndrome.

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Lee, Younghak; Yi, Hyon Seung; Kim, Hae Ri; Joung, Kyong Hye; Kang, Yea Eun; Lee, Ju Hee; Kim, Koon Soon; Kim, Hyun Jin; Ku, Bon Jeong; Shong, Minho

2017-09-01

Cushing syndrome is characterized by glucose intolerance, cardiovascular disease, and an enhanced systemic inflammatory response caused by chronic exposure to excess cortisol. Eosinopenia is frequently observed in patients with adrenal Cushing syndrome, but the relationship between the eosinophil count in peripheral blood and indicators of glucose level in patients with adrenal Cushing syndrome has not been determined. A retrospective study was undertaken of the clinical and laboratory findings of 40 patients diagnosed with adrenal Cushing syndrome at Chungnam National University Hospital from January 2006 to December 2016. Clinical characteristics, complete blood cell counts with white blood cell differential, measures of their endocrine function, description of imaging studies, and pathologic findings were obtained from their medical records. Eosinophil composition and count were restored by surgical treatment of all of the patients with adrenal Cushing disease. The eosinophil count was inversely correlated with serum and urine cortisol, glycated hemoglobin, and inflammatory markers in the patients with adrenal Cushing syndrome. Smaller eosinophil populations in patients with adrenal Cushing syndrome tend to be correlated with higher levels of blood sugar and glycated hemoglobin. This study suggests that peripheral blood eosinophil composition or count may be associated with serum glucose levels in patients with adrenal Cushing syndrome. Copyright © 2017 Korean Endocrine Society

Disposable glucose test strip for whole blood with integrated sensing/diffusion-limiting layer

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Chen Zhencheng [Department of Biomedical Engineering, School of Info-Physics and Geomatics Engineering, Central South University, Changsha 410083 (China); Fang Cheng, E-mail: fangpingchuan@163.co [Department of Biomedical Engineering, School of Info-Physics and Geomatics Engineering, Central South University, Changsha 410083 (China); Wang Hongyan; He Jishan [Department of Biomedical Engineering, School of Info-Physics and Geomatics Engineering, Central South University, Changsha 410083 (China)

2009-12-30

A disposable glucose test strip with an integrated sensing/diffusion-limiting layer was developed. A formulation containing filler, glucose oxidase and electronic mediator was screen-printed over two carbon electrodes to form an integrated sensing/diffusion-limiting layer. On rehydration, the integrated layer does not break up, but swells to form a gelled and three-dimensional meshy reaction zone on the surface of the underlying conductive elements in which reactants and mediator move freely, but interfering species such as red blood cells containing oxygenated hemoglobin are excluded. On the same time, the integrated layer maintains a rate of permeation of the analyte through it with a variation of less than 10% at temperatures ranging from 15 deg. C to 42 deg. C. This biosensor is substantially insensitive to interferents and essentially independent to relevant temperature, which provides a more reliable reading of actual blood glucose value in human whole blood.

Functional relevance of protein glycosylation to the pro-inflammatory effects of extracellular matrix metalloproteinase inducer (EMMPRIN) on monocytes/macrophages.

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Ge, Heng; Yuan, Wei; Liu, Jidong; He, Qing; Ding, Song; Pu, Jun; He, Ben

2015-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) is an important pro-inflammatory protein involved in the cellular functions of monocytes/macrophages. We have hypothesized that high-level heterogeneousness of protein glycosylation of EMMPRIN may have functional relevance to its biological effects and affect the inflammatory activity of monocytes/macrophages. The glycosylation patterns of EMMPRIN expressed by monocytes/macrophages (THP-1 cells) in response to different extracellular stimuli were observed, and the structures of different glycosylation forms were identified. After the purification of highly- and less-glycosylated proteins respectively, the impacts of different glycosylation forms on the pro-inflammatory effects of EMMPRIN were examined in various aspects, such as cell adhesion to endothelial cells, cell migrations, cytokine expression, and activation of inflammatory signalling pathway. 1) It was mainly the highly-glycosylated form of EMMPRIN (HG-EMMPRIN) that increased after being exposed to inflammatory signals (PMA and H2O2). 2) Glycosylation of EMMPRIN in monocytes/macrophages led to N-linked-glycans being added to the protein, with the HG form containing complex-type glycans and the less-glycosylated form (LG) the simple type. 3) Only the HG-EMMPRIN but not the LG-EMMPRIN exhibited pro-inflammatory effects and stimulated inflammatory activities of the monocytes/macrophages (i.e., activation of ERK1/2 and NF-κB pathway, enhanced monocyte-endothelium adhesion, cell migration and matrix metalloproteinase -9 expression). Post-transcriptional glycosylation represents an important mechanism that determines the biological effects of EMMPRIN in monocytes/macrophages. Glycosylation of EMMPRIN may serve as a potential target for regulating the inflammatory activities of monocytes/macrophages.