muramidase and Diabetes-Mellitus--Type-2

Metabolic syndrome and type 2 diabetes (T2DM) resulting from sustained hyperglycemia are considered as risk factors for cardiovascular disease (CVD) but the mechanism for their contribution to cardiopathogenesis is not well understood. Hyperglycemia induces nonenzymatic glycation of protein-yielding advanced glycation end products (AGE), which are postulated to stimulate interleukin-6 (IL-6) expression, triggering the liver to secrete tissue necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP) that contribute to CVD pathogenesis. Although the high prevalence of periodontitis among individuals with diabetes is well known by dental researchers, it is relatively unrecognized in the medical community. The expression of the same proinflammatory mediators implicated in hyperglycemia (i.e., IL-6, TNF-alpha, and CRP) have been reported to be associated with periodontal disease and increased risk for CVD. We will review published evidence related to these 2 pathways and offer a consensus.

Topics: Carbohydrate Metabolism; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Endothelium, Vascular; Focal Infection, Dental; Glycation End Products, Advanced; Humans; Hyperglycemia; Inflammation Mediators; Metabolic Syndrome; Muramidase; Periodontitis; Salivary Proteins and Peptides

Lysozyme is a bactericidal enzyme whose structure and functions change in diabetes. Chemical chaperones are small molecules including polyamines (e.g. spermine), amino acids (e.g. L-lysine) and polyols (e.g. glycerol). They can improve protein conformation in several stressful conditions such as glycation. In this study, the authors aimed to observe the effect of L-lysine as a chemical chaperone on structure and function of glycated lysozyme. In this study, in vitro and in vivo effects of L-lysine on lysozyme glycation were investigated. Lysozyme was incubated with glucose and/or L-lysine, followed by an investigation of its structure by electrophoresis, fluorescence spectroscopy, and circular dichroism spectroscopy and also assessment of its bactericidal activity against M. lysodeikticus. In the clinical trial, patients with type 2 diabetes mellitus (T2DM) were randomly divided into two groups of 25 (test and control). All patients received metformin and glibenclamide for a three months period. The test group was supplemented with 3 g/day of L-lysine. The quantity and activity of lysozyme and other parameters were then measured. Among the test group, L-lysine was found to reduce the advanced glycation end products (AGEs) in the sera of patients with T2DM and in vitro condition. This chemical chaperone reversed the alteration in lysozyme structure and function due to glycation and resulted in increased lysozyme activity. Structure and function of glycated lysozyme are significantly improved by l-lysine; therefore it can be considered an effective therapeutic supplementation in T2DM, decreasing the risk of infection in these patients.

Topics: Adult; Diabetes Mellitus, Type 2; Dietary Supplements; Female; Glucose; Glycation End Products, Advanced; Glycosylation; Humans; Lysine; Male; Muramidase; Protein Conformation

Irreversible aggregation of misfolded proteins is the underlying molecular cause of numerous pathologies, including diabetes type 2, Alzheimer's, and Parkinson's diseases. Such an abrupt protein aggregation results in the formation of small oligomers that can propagate into amyloid fibrils. A growing body of evidence suggests that protein aggregation can be uniquely altered by lipids. However, the role of the protein-to-lipid (P:L) ratio on the rate of protein aggregation, as well as the structure and toxicity of corresponding protein aggregates remains poorly understood. In this study, we investigate the role of the P:L ratio of five different phospho- and sphingolipids on the rate of lysozyme aggregation. We observed significantly different rates of lysozyme aggregation at 1:1, 1:5, and 1:10 P:L ratios of all analyzed lipids except phosphatidylcholine (PC). However, we found that at those P:L ratios, structurally and morphologically similar fibrils were formed. As a result, for all studies of lipids except PC, mature lysozyme aggregates exerted insignificantly different cell toxicity. These results demonstrate that the P:L ratio directly determines the rate of protein aggregation, however, has very little if any effect on the secondary structure of mature lysozyme aggregates. Furthermore, our results point to the lack of a direct relationship between the rate of protein aggregation, secondary structure, and toxicity of mature fibrils.

Topics: Amyloid; Diabetes Mellitus, Type 2; Humans; Lipids; Muramidase; Protein Aggregates

Protein fibrillation is a phenomenon associated with misfolding and the production of highly ordered nanofibrils, which may cause serious degenerative diseases such as Parkinson's disease, Alzheimer's disease, and type 2 diabetes. Upon contact with biological fluids, the nanomaterials are immediately covered by proteins and interact with them. In this study, the effects of Graphene NanoPlateles (Plain-GNPs) and their modified forms with a carboxyl group (GNPs -COOH) and an amine group (GNPs -NH

Topics: Amyloid; Animals; Chickens; Diabetes Mellitus, Type 2; Egg White; Graphite; Muramidase; Neuroblastoma

The tendency of polypeptide chains to deviate from their conventional protein folding pathway and instead get trapped as off-pathway intermediates, has been a matter of great concern. These off-pathway intermediates eventually lead to the formation of insoluble, ordered fibrillar aggregates called amyloids, which are responsible for a host of neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Type II diabetes. In spite of extensive research, development of an effective therapeutic strategy against amyloidosis still remains elusive. In recent times, carbon quantum dots (CQD) have grabbed the attention of researchers against amyloidogenesis due to their ease of preparation, aqueous soluble nature, unique optical properties, high surface to volume ratio, physio-chemical properties, semi-conducting nature and mainly biocompatible. In the current study, we have reported an easy-to-prepare procedure for synthesis of amine group surface functionalized CQDs from commonly available kitchen spices with anti-oxidant properties. The as-synthesized CQDs were evaluated for their anti-amyloidogenic properties towards Hen Egg White Lysozyme (HEWL). Our results clearly show that the surfaced functionalized CQDs were able to interact with HEWL, thereby forming a stable complex, which was resistant towards amyloid formation and instead lead to the formation of non-toxic globular aggregates.

Topics: Amines; Amyloid; Diabetes Mellitus, Type 2; Egg White; Humans; Muramidase; Protein Aggregates; Quantum Dots

Proteins, under certain circumstances such as defective quality control mechanism, mutations and altered environmental conditions, undergo misfolding and assemble into highly ordered beta-sheet structured fibrillar aggregates called amyloid fibrils. Formation of amyloid is seen in most of the protein linked degenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, Type II diabetes mellitus and many more. Amyloid fibril forms via intermediate state(s), and is known to follow a nucleated condensation polymerization mechanism. Though extensive research is being carried out towards finding a therapeutic solution to the amyloidosis, an effective treatment to these diseases still remains elusive and also the mechanism of amyloidogenesis largely remains unclear. In recent times, carbon quantum dots (CQDs) are gaining the attention of researchers due to their semi-conductive nature, excellent physio-chemical properties, high surface to volume ratio, optical properties and mainly bio-compatibility. In the current study, we have synthesized CQDs from commonly available kitchen spice mix and explored their role in amyloidogenesis using hen egg white lysozyme (HEWL) as a model protein. The results clearly demonstrate the amyloid inhibitory as well as disaggregation potential of CQD by forming a stable complex with HEWL and thereby increasing the energy barrier for the aggregation process.

Topics: Amyloid; Animals; Carbon; Chickens; Diabetes Mellitus, Type 2; Egg White; Humans; Muramidase; Protein Aggregates; Quantum Dots

Was to analyze the effectiveness of therapeutic and preventive measures aimed at reducing hyperesthesia of hard dental tissues in patients with background somatic diseases.. The study involved 113 patients with increased tooth sensitivity and treated in the gastroenterological and endocrinological departments of the S.M. Kirov City Clinical Hospital No.3» in Astrakhan in the period from 2018 to 2021 at the age of 26-43 years. The main group included 52 patients with confirmed diagnoses of gastric and duodenal ulcer, pancreatitis and type II diabetes mellitus who were treated for dental hyperesthesia with an integrated approach. The control group included 61 patients with periodontal disease without background somatic pathologies in whom hyperesthesia was treated by remineralizing therapy. The effectiveness of the treatment was determined in dynamics on the 10th and 40th days of treatment using OHI-S, PMA indices, dental hypersensitivity prevalence (DHP), dental hypersensitivity intensity (DHI), Dental Sensitivity Index (DSI), Efficacy of Dental Sensitivity Index (EDSI). In addition, the pH of saliva, the activity of lysozyme and S-IgA, and the levels of cytokines IL-1β, IL-4, IL-6, and IL-8 were determined.. The average value of OHI-S in the main group on the 10th day of treatment decreased from 2.25±0.12 (poor level of hygiene) to 1.47±0.09 (satisfactory level). The PMA index in the main group also tended to decrease from 32.1±1.44% (moderate degree of gingivitis) to 20.5±2.08% (mild degree) on the 10th day of treatment. The average values of DPH, DPI, EDSI and DSI in the main group had a noticeable decrease already on the 10th day from the start of treatment (from 12.3±1.66% to 2.1±1.22%; from 2.5±0.48 to 1.2±0.16; from 48.3±1.14% to 40.8±1.71%; from 42.1±2.07% to 20.8±1, 65% respectively). In the main group on the 10th and 40th day of treatment the pH values of non-stimulated and stimulated saliva stabilized (from 4.61±0.12 to 6.94±0.07 and from 5.47±0.21 to 7.42±0.24, respectively), the activity of lysozyme increased (from 45.97±1.46% to 55.19±0.96%) alongside with secretory IgA (from 0.17±0.02 to 0.33±0.21 mg/ml). Also, indicators of cytokines IL-1β, IL-4, IL-6, IL-8 tended to improve. The analysis of the control group revealed persistent mean values that did not yield to significant changes either in the course of treatment.. Thus, in patients of the main group, the results obtained indicate an improvement in the dental status and activation of cytokine regulation, providing a combination of active components of the mineral complex. In controls the method of remineralizing therapy for tooth hyperesthesia alleviated dental hypersensitivity, but without significant improvement of the laboratory results.. Проанализировать эффективность лечебно-профилактических мероприятий, направленных на снижение гиперестезии твердых тканей зубов, у пациентов с фоновыми соматическими заболеваниями.. В исследовании приняли участие 113 пациентов, имевшие повышенную чувствительность зубов и проходившие лечение в гастроэнтерологическом и эндокринологическом отделениях «Городская клиническая больница №3 им. С.М. Кирова» г. Астрахани в период с 2018 по 2021 г. в возрасте 26—43 лет. В основную группу вошли 52 пациента с язвенной болезнью желудка и двенадцатиперстной кишки, панкреатитом или сахарным диабетом II типа, которым проводилось лечение гиперестезии зубов с применением комплексного подхода. В контрольную группу вошел 61 пациент с заболеваниями пародонта без фоновых соматических патологий, у которых лечение гиперестезии проводилось методом реминерализирующей терапии. Эффективность лечения определяли в динамике на 10-й и 40-й дни лечения с помощью индексов гигиены OHI-S, папиллярно-маргинально-альвеолярного индекса РМА в модификации Parma, индексов распространенности гиперестезии зубов (ИРГЗ), интенсивности гиперестезии зубов (ИИГЗ), сенситивности зубов (ИСЗ О-У), эффективности сенситивности зубов (СЗ). Помимо этого определяли pH слюны, активность лизоцима и S-IgA, уровни цитокинов ИЛ-1β, ИЛ-4, ИЛ-6, ИЛ-8.. Показатели индекса OHI-S в основной группе уже на 10-й день лечения снизились с 2,25±0,12 (неудовлетворительный уровень гигиены) до 1,47±0,09 (удовлетворительный уровень). Показатели индекса PMA в основной группе также имели тенденцию к снижению с 32,1±1,44% (средняя степень гингивита) до 20,5±2,08% (легкая степень) на 10-й день лечения. Средние значения показателей индексов ИРГЗ, ИИГЗ, СЗ, ИСЗ О-У в основной группе заметно снизились уже на 10-й день от начала лечения (с 12,3±1,66% до 2,1±1,22%; с 2,5±0,48 до 1,2±0,16; с 48,3±1,14% до 40,8±1,71%; с 42,1±2,07% до 20,8±1,65% соответственно). В основной группе у пациентов на 10-й и далее на 40-й день лечения наблюдалось улучшение показателя pH нестимулированной и стимулированной слюны (с 4,61±0,12 до 6,94±0,07 и с 5,47±0,21 до 7,42±0,24 соответственно), возросли показатели активность лизоцима (с 45,97±1,46% до 55,19±0,96%) вместе с показателями секреторного IgA (с 0,17±0,02 до 0,33±0,21 мг/мл). Также улучшились показатели цитокинов ИЛ-1β, ИЛ-4, ИЛ-6, ИЛ-8. Анализ контрольной группы выявил стойкие средние показатели индексов, которые значительно не менялись в ходе лечения.. У пациентов основной группы полученные результаты свидетельствуют об улучшении стоматологического статуса и активации цитокиновой регуляции. У пациентов контрольной группы с помощью реминерализирующей терапии удалось нивелировать гиперчувствительность зубов, но лабораторные показатели корректировались незначительно.

Topics: Adult; Dentin Sensitivity; Diabetes Mellitus, Type 2; Humans; Interleukin-4; Interleukin-6; Interleukin-8; Muramidase; Saliva; Tooth Remineralization

diabetes mellitus is associated with a high prevalence of oral infections. However, it is unclear how diabetes impacts oral innate antimicrobial proteins. This study evaluated salivary lysozyme and histatins, two major innate antimicrobial proteins, in patients with diabetes and non-diabetic controls.. a cross-sectional study where salivary lysozyme and histatins were measured alongside plasma glucose levels. Values of the salivary proteins were compared between the two groups; their association with glucose levels was also established using correlation and regression analysis.. one hundred and fifty-one participants were recruited for this study, 85 (56.3%) of them had type 2 diabetes mellitus with a median fasting plasma glucose of 108.8 mg/dl (IQR 91.2-134.8) while the remaining 66 (43.7%) healthy non-diabetic controls had a median random plasma glucose of 101 mg/dl (IQR 89-112). The median salivary lysozyme was 32.5 ng/ml (IQR 25.0-39.6) in the group with diabetes and 36.4 ng/ml (IQR 31.4-42.1; p=0.01) in the non-diabetic control group. The median salivary histatins was 9.2 ng/ml (IQR 7.6 -10.2) in the group with diabetes and 14.7 ng/ml (IQR12.8-16.5; p<0.001) in the non-diabetic control group. Salivary lysozyme (r = -0.127; p =0.163) and histatins (r = -0.025; p = 0.424) were both negatively correlated with plasma glucose levels, and logistic regression showed that patients with diabetes are more likely to have lower levels of salivary lysozyme (0.957; p=0.013) and histatins (0.527; p<0.001).. patients with diabetes had reduced levels of salivary lysozyme and histatins, this could provide an insight into the associated high oral infection rates.

Topics: Anti-Infective Agents; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Histatins; Humans; Immunity, Innate; Muramidase; Nigeria; Saliva; Salivary Proteins and Peptides; Tertiary Care Centers

Aggregation of protein causes various diseases including Alzheimer's disease, Parkinson's disease, and type II diabetes. It was found that aggregation of protein depends on many factors like temperature, pH, salt type, salt concentration, ionic strength, protein concentration, co solutes. Here we have tried to capture the aggregation mechanism and pathway of hen egg white lysozyme using molecular dynamics simulations at two different temperatures; 300 K and 340 K. Along with the all atom simulations to get the atomistic details of aggregation mechanism, we have used coarse grained simulation with MARTINI force field to monitor the aggregation for longer duration. Our results suggest that due to the aggregation, changes in the conformation of lysozyme are more at 340 K than at 300 K. The change in the conformation of the lysozyme at 300 K is mainly due to aggregation where at 340 K change in conformation of lysozyme is due to both aggregation and temperature. Also, a more compact aggregated system is formed at 340 K.

Topics: Diabetes Mellitus, Type 2; Humans; Molecular Conformation; Molecular Dynamics Simulation; Muramidase; Temperature

The assembly of proteins into amyloidogenic aggregates underlies the onset and symptoms of several pathologies, including Alzheimer's disease, Parkinson's disease and type II diabetes. Among the efforts for fighting these diseases, there is a great demand for developing novel, fast and reliable methods for in vitro screening of new drugs that may suppress or reverse amyloidogenesis. Recent studies unravelled a progressive increase in a blue autofluorescence upon amyloid formation originated from many different proteins, including the peptide amyloid-β, lysozyme or insulin. Herein, we propose a drug screening method using this property, avoiding the use of external probe dyes. We demonstrate that the inhibition of lysozyme amyloid formation by means of two known inhibitors, tartrazine and amaranth, can be monitored based on the autofluorescence of lysozyme amyloid aggregates. Our results show that amyloid luminescence is an intrinsic property that can be potentially applied in a screening assay, allowing the ranking of drug efficiency. The assays demonstrated here are fast to perform and suitable for scaling using microplate assays, configuring a new sensitive and economically feasible method.

Topics: Amyloid; Amyloid beta-Peptides; Biomarkers; Diabetes Mellitus, Type 2; Humans; Muramidase

Amyloid fibrillation has been implicated in many neurodegenerations, dialysis-related amyloidosis, type II diabetes and more than 30 other amyloid-related diseases. Nanomaterials as potential inhibitors of amyloid fibrillation have attracted increasing interests. In the present study, the effects of gold nanorods (AuNRs) and nanoparticles (AuNPs) on amyloid fibrillation were investigated using hen egg white lysozyme (HEWL) as a model system. Our results indicated that AuNRs and AuNPs, especially AuNRs, present significant inhibitory effects on HEWL amyloid fibril formation during all the kinetic processes, from nucleation to elongation and equilibration stages. The stronger adsorption capacity of HEWL on AuNRs surface is the key mechanism of inhibition of HEWL amyloid fibrillation. Furthermore, AuNRs lead to more stable α-helix conformation and hydrophobic microenvironment of aromatic side groups in HEWL molecules, which facilitate the system to form small amorphous aggregates rather than oligomer, profibril or mature fibril.

Topics: Amyloid; Diabetes Mellitus, Type 2; Gold; Muramidase; Nanoparticles; Nanotubes; Renal Dialysis

Understanding the interplay between adiposity, inflammation, and cardiovascular complications in type 2 diabetes mellitus (T2DM) remains a challenge. Signaling from adipocytes is considered important in this context. Adiponectin is the most abundant adipocytokine and has been associated with various measures of cardiovascular disease (CVD). This study examines the relationships between genetic variants in the adiponectin (ADIPOQ) and adiponectin-related signaling pathway genes and measures of subclinical CVD (vascular calcified plaque and carotid intima-media thickness), plasma lipids, and inflammation in T2DM.. Single-nucleotide polymorphisms (SNPs) in ADIPOQ (n = 45), SNPs tagging ADIPOR1 (n = 6), APIPOR2 (n = 8), APPL1 (n = 6) and known rare coding variants in KNG1 (n = 3) and LYZL1 (n = 3) were genotyped in 1220 European Americans from the family-based Diabetes Heart Study. Associations between SNPs and phenotypes of interest were assessed using a variance components analysis with adjustment for age, sex, T2DM-affected status, and body mass index.. There was minimal evidence of association between SNPs in the adiponectin signaling pathway genes and measures of calcified plaque; eight of the 71 SNPs showed evidence of association with subclinical CVD (P = 0.007-0.046) but not with other phenotypes examined. Nine additional SNPs were associated with at least one of the plasma lipid measures (P = 0.008-0.05).. Findings from this study do not support a significant role for variants in the adiponectin signaling pathway genes in contributing to risk for vascular calcification in T2DM. However, further understanding the interplay between adiposity, plasma lipids, and inflammation may prove important in the prediction and management of cardiovascular complications in T2DM.

Topics: Adaptor Proteins, Signal Transducing; Adiponectin; Aged; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 2; Female; Genotype; Humans; Inflammation; Lipids; Male; Middle Aged; Muramidase; Obesity; Phenotype; Plaque, Atherosclerotic; Polymorphism, Single Nucleotide; Receptors, Adiponectin; Signal Transduction; Tunica Intima; Tunica Media; Vascular Calcification; White People

Exchangeable low-density lipoprotein (LDL)-associated proteins can affect the atherogenic properties of LDL. Our aim was to analyse the protein composition of LDL from individuals with or without type 2 diabetes and the metabolic syndrome (T2DM) in relation to other LDL particle characteristics, to assess whether certain proteins associate more with certain subclasses of LDL typical for T2DM, such as small, apoCIII-rich LDL.. Low-density lipoprotein from two cohorts of 61-year-old men (n = 19 and 64) with or without T2DM was isolated using size-exclusion chromatography or deuterium oxide-based ultracentrifugation. LDL-associated proteins were identified using mass spectrometry and quantified using two-dimensional gel electrophoresis or enzyme-linked immunosorbent assay. Differently expressed LDL-associated proteins apolipoprotein (apo)J and lysozyme were also measured in serum from a third cohort of women (n = 71) with or without T2DM. Lysozyme binding to advanced glycation end product (AGE)-LDL was examined in vitro.. ApoJ and lysozyme were increased in LDL particles with increased apoCIII content and decreased cholesterol content. When isolated with size-exclusion chromatography, LDL from individuals with T2DM contained more apoJ and lysozyme and less apoA1 than LDL from control individuals. LDL content of apoJ correlated with a smaller LDL particle size. Serum levels of lysozyme, but not apoJ, were increased in individuals with T2DM. In vitro, lysozyme associated more with AGE-LDL than with unmodified LDL.. Our results indicate that apoJ and lysozyme are increased in LDL with characteristics of small dense LDL in T2DM. Small dense LDL is easily glycated, and the increased affinity of lysozyme for AGE-LDL provides a possible partial explanation for an increase lysozyme in LDL from those with type 2 diabetes.

Topics: Cholesterol; Chromatography, Gel; Clusterin; Cohort Studies; Diabetes Mellitus, Type 2; Electrophoresis, Gel, Two-Dimensional; Female; Glycation End Products, Advanced; Humans; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Muramidase

Obese human subjects have increased protein-tyrosine phosphatase (PTPase) activity in adipose tissue that can dephosphorylate and inactivate the insulin receptor kinase. To extend these findings to skeletal muscle, we measured PTPase activity in the skeletal muscle particulate fraction and cytosol from a series of lean controls, insulin-resistant obese (body mass index > 30) nondiabetic subjects, and obese individuals with non-insulin-dependent diabetes. PTPase activities in subcellular fractions from the nondiabetic obese subjects were increased to 140-170% of the level in lean controls (P < 0.05). In contrast, PTPase activity in both fractions from the obese subjects with non-insulin-dependent diabetes was significantly decreased to 39% of the level in controls (P < 0.05). By immunoblot analysis, leukocyte antigen related (LAR) and protein-tyrosine phosphatase 1B had the greatest increase (threefold) in the particulate fraction from obese, nondiabetic subjects, and immunodepletion of this fraction using an affinity-purified antibody directed at the cytoplasmic domain of leukocyte antigen related normalized the PTPase activity when compared to the activity from control subjects. These findings provide further support for negative regulation of insulin action by specific PTPases in the pathogenesis of insulin resistance in human obesity, while other regulatory mechanisms may be operative in the diabetic state.

Topics: Adult; Body Weight; Cell Fractionation; Chromatography, Gel; Deoxyglucose; Diabetes Mellitus; Diabetes Mellitus, Type 2; Humans; Immunoblotting; Insulin; Insulin Resistance; Middle Aged; Muramidase; Muscle, Skeletal; Obesity; Phosphoprotein Phosphatases; Phosphorylation; Protein Tyrosine Phosphatases; Receptor-Like Protein Tyrosine Phosphatases, Class 4; Receptor, Insulin; Receptors, Cell Surface; Substrate Specificity

Early morning urine specimens were obtained from two groups of non-insulin dependent diabetic patients and a group (43 subjects) of normal controls. The diabetic patients were divided into two subgroups according to the degree of diabetic control as judged by their glycosylated haemoglobin (HbA1) levels (well-controlled, 47 subjects; poorly controlled, 51 subjects). The concentration of the low-molecular-weight enzyme (lysozyme) was determined in each urine specimen and related to the concentration of creatinine (lysozyme/creatinine). The mean urinary lysozyme concentration was higher in each of the two diabetic groups as compared with the control group. However, it was not significantly different between the two diabetic groups. These result suggest that there is no association between the degree of glycaemic control and tubular proteinuria.

Topics: Adult; Aged; Blood Glucose; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Muramidase; Proteinuria

Renal tubular function was investigated in 98 non-insulin-dependent and 18 insulin-dependent diabetics under conditions of standard glycemic control. Mean urinary excretion of lysozyme, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) in both Albustix-negative and positive patients were significantly elevated above the control range. The increased excretion of lysozyme, beta 2-microglobulin and NAG was found in 21, 55 and 62% of the normoalbuminuric patients, and in 40, 57 and 74% of the microalbuminuric patients, respectively. Besides the parameters cited above, urinary acid-soluble glycoprotein (ASP) was measured to assess its potential as an indicator of early renal dysfunction. Mean urinary ASP excretion was also elevated in both Albustix-negative and positive patients. The albumin/ASP ratio increased as nephropathy advanced. Such a mode of excretion was similar to those of low-molecular-weight proteins (lysozyme and beta 2-microglobulin). The results of multiple regression analysis showed that serum creatinine most highly correlated with the excretion of the urinary proteins except for NAG.

Topics: Acetylglucosaminidase; Adult; Albuminuria; beta 2-Microglobulin; Biomarkers; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Kidney Tubules; Male; Middle Aged; Muramidase; Proteinuria; Regression Analysis

Topics: Adult; Aged; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enzyme Activation; Humans; Middle Aged; Muramidase; Urinary Tract Infections

Seeking to study whether measurement of lysozyme (EC 3.2.1.17) in urine by a reliable radioimmunoassay can provide a suitable index of renal tubular function and how lysozymuria develops in temporal relation to proteinuria in diabetic nephropathy, we have compared the urinary excretion of lysozyme and beta 2-microglobulin with the 15-min excretion rate of phenolsulfonphthalein in 39 patients with Type 2 (non-insulin-dependent) diabetes and investigated the temporal relation between the onset of lysozymuria and proteinuria in 15 patients with Type 1 (insulin-dependent) diabetes. The concentrations of lysozyme and beta 2-microglobulin in urine increased in proportion to the decrease in the rate of excretion of phenolsulfonphthalein in these patients. The coefficient of correlation between lysozyme concentration and the 15-min excretion rate of phenolsulfonphthalein (r = -0.70) was higher than that between beta 2-microglobulin concentration and the 15-min excretion rate of phenolsulfonphthalein (r = -0.46). Abnormally high lysozymuria, suggesting the existence of tubular dysfunction, was demonstrated in six of the patients with Type 1 diabetes who showed no proteinuria or only a slight increase in urinary protein excretion. Lysozymuria may thus be added to a list of the indicators for diabetic nephropathy.

Topics: Adolescent; Adult; Aged; beta 2-Microglobulin; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Kidney Tubules; Middle Aged; Muramidase; Phenolsulfonphthalein; Proteinuria