Plasma Proteins Of Type Research Articles

The causal relationship between plasma protein-to-protein ratios and type 2 diabetes and its complications: Proteomics mendelian randomization study.

In recent years, proteomics research has surged, with numerous observational studies identifying associations between plasma proteins and type 2 diabetes. However, research specifically focusing on the ratios of plasma proteins in type 2 diabetes remains relatively scarce. This study primarily employed a two-sample, two-step Mendelian randomization (MR) approach, leveraging genetic data from several large, publicly accessible genome-wide association studies, wherein single nucleotide polymorphisms served as proxies for exposures and diseases. Within this framework, we applied two-sample MR to assess the associations between the 2821 plasma protein-to-protein ratios and type 2 diabetes along with its complications and utilized reverse MR to confirm the unidirectionality of these causal relationships. In addition, we employed two-step MR to investigate the potential mediating role of body mass index in these associations. To augment the robustness of our findings, we systematically implemented a series of sensitivity analyses. The results gleaned from the inverse-variance weighted method elucidated that a cumulative sum of 23 protein-to-protein ratios bore a causal nexus with type 2 diabetes across both sample cohorts. With each incremental elevation of 1 standard deviation in the genetically anticipated protein-to-protein ratio, the susceptibility to type 2 diabetes oscillated from 0.93 (95% confidence interval: 0.87, 1.00) for the CNTN3/NCSS1 protein level ratio to 1.13 (1.06, 1.22) for the DBNL/NCK2 protein level ratio. Moreover, a tally of eight protein-to-protein ratios correlated with a minimum of one complication linked to type 2 diabetes. Diverse sensitivity analyses corroborated the robustness of these observations. The outcomes of our investigation unveiled correlations between 23 plasma protein-to-protein ratios and type 2 diabetes, with eight of these ratios entwined with complications of type 2 diabetes. These discoveries offer novel perspectives on the diagnosis and management of type 2 diabetes and its associated complications.

ITRAQ plasma proteomics analysis for candidate biomarkers of type 2 incipient diabetic nephropathy

BackgroundDiabetic nephropathy is the most frequent cause of end-stage renal disease worldwide. Identification of biomarkers for diabetic nephropathy for early diagnosis may be the key to avoiding damage from this condition.MethodsProteomic iTRAQ technology was first used to identify differentially expressed plasma proteins in type 2 incipient diabetic nephropathy (IDN) using a Q-Exactive mass spectrometer.ResultsCompared with controls, 57 proteins (32 upregulated and 25 downregulated proteins) were identified. Furthermore, the gelsolin, collectin-11, PTPRJ, and AKAP-7 proteins were confirmed by Western blots as candidate biomarkers for type 2 IDN through ROC analysis.ConclusionsThese findings offer a theoretical basis for the early treatment of diabetic nephropathy.

Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients.

Advanced glycation end products (AGEs) are posttranslational modifications formed non-enzymatically from the reaction of carbohydrates and their degradation products with proteins. Accumulation of AGEs is associated with the progression of severe diabetic complications, for example, and elevated tissue levels of AGEs might even predict these pathologies. As AGE formation is often site-specific, mapping of these modification sites may reveal more sensitive and specific markers than the global tissue level. Here, 42 AGE modifications were identified in a bottom-up proteomic approach by tandem mass spectrometry, which corresponded to 36 sites in 22 high to medium abundant proteins in individual plasma samples obtained from type 2 diabetes mellitus (T2DM) patients with long disease duration (>10years). Major modifications were glarg (11 modification sites) and carboxymethylation (5) of arginine and formylation (8), acetylation (7), and carboxymethylation (7) of lysine residues. Relative quantification of these sites in plasma samples obtained from normoglycemic individuals (n = 47) and patients with T2DM being newly diagnosed (n = 47) or of medium (2-5years, n = 20) and long disease duration (>10years, n = 20) did not reveal any significant differences.

Glycation of plasma proteins in type II diabetes lowers the non-covalent interaction affinities for dietary polyphenols

Diabetes is characterized by an elevated level of glucose in the blood. This glucose can form covalent adducts with plasma proteins through a non-enzymatic process known as glycation. It has been suggested that the increasing glycation can influence the ability of plasma proteins to bind to small molecules. Herein, the difference between healthy human plasma proteins (HPP) and type II diabetes plasma proteins (TPP) in binding small molecules was investigated. TPP showed about 1-10 times lower affinities for polyphenols than HPP. The values of lg K(a)(HPP) are positive proportional to the values of lg K(a)(TPP) with excellent linear relationship. The glycation of HPP decreased the affinities for HPP by about 1.17 to 16.6 times. The difference between HPP-polyphenol interaction and TPP-polyphenol interaction was bigger for the more lipophilic polyphenols. The affinities for TPP or HPP slightly decreased with increasing hydrogen bond donor numbers of polyphenols and hardly changed with hydrogen bond acceptor numbers.

Protein oxidation biomarkers in plasma of type 2 diabetic patients

Objectives To evaluate oxidative stress and the extent of oxidation of plasma proteins in type 2 diabetic patients. Design and methods Study was carried out on blood from 31 diabetic patients of both sexes (mean age = 58 ± 7; duration of diabetes 12 ± 5 years) and healthy age and sex matched normal subjects. Biomarkers of protein oxidation; plasma protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and –SH group and free radical scavenging capacity of plasma was measured. Results PCO and AOPPS levels were significantly ( P < 0.005) higher in diabetic patients in comparison to healthy volunteers. Reduced free radical scavenging capacity ( P < 0.001) and –SH group ( P < 0.05) was observed in plasma of type 2 diabetic patients. Conclusions Our data suggest that diabetics are susceptible to protein oxidation. Oxidative modulation of proteins due to reduced radical scavenging activity of plasma patients may be one of the reasons of altered physiological processes in type 2 diabetic patients.

Differentially displayed proteins as a tool for the development of type 2 diabetes

Type 2 diabetes is a complex disease that still requires a great deal of work to be carried out to understand the pathophysiology. Recently, researchers have focused on studying the organs and tissues known to be involved in the development of the type 2 phenotype using a proteomic approach. Little work has been reported on plasma of type 2 diabetics in whom the clinical status has been well characterized. In this study, changes in plasma proteins of type 2 diabetics were investigated by proteomic analysis in well-characterized individuals with type 2 diabetes (early and late stage) and control groups (with or without a family history of diabetes). Samples were analysed by two-dimensional gel electrophoresis and significantly differentiated proteins were identified by nano-LC-ESI-MS. A total of 12 protein signatures that were differentially displayed with high significance compared with controls were selected. Four of the differentially displayed proteins were identified as haptoglobin alpha2, haptoglobin Hp2(fragment) and transthyretin and Chain A (formerly prealbumin), and all were up-regulated. Thiol-specific antioxidant protein, Chain A, tertiary structures of three amyloidogenic transthretin variants and haptoglobin-related protein precursor were all down-regulated in controls with a family history of diabetes, early and late diabetic patients in comparison with the control. A proteomic-based approach was used to discover and identify the differentially expressed proteins in various states of type 2 diabetes.

Identification of Amadori-Modified Plasma Proteins in Type 2 Diabetes and the Effect of Short-Term Intensive Insulin Treatment

Growing evidence supports that nonenzymatic glycation products may cause hyperglycemia-induced diabetes complications. Amadori-modified proteins are the intermediate products of nonenzymatic glycation and constitute the forms of glycated proteins in diabetes. The objective of the current study was to utilize two-dimensional gel electrophoresis, Western blot, and mass spectrometry to identify Amadori-modified plasma proteins in type 2 diabetic patients with poor glycemic control and assess the impact of short-term insulin treatment on the glycation of these proteins. We compared eight type 2 diabetic subjects (aged 56 +/- 3 years and BMI 29.7 +/- 0.9 kg/m(2)) with an average diabetes duration of 8.5 years (range 3-19) with equal numbers of weight-matched (aged 56 +/- 2 years and BMI 30.1 +/- 10.0 kg/m(2)) and lean (aged 58 +/- 2 years and BMI 25 +/- 00.5 kg/m(2)) nondiabetic subjects who have no first-degree relatives with diabetes. Two separate blood samples were collected from the type 2 diabetic subjects, one following 2 weeks of withdrawal of all antidiabetic medications (T(2)D-; plasma glucose 12.6 +/- 1.0 mmol/l) and another following 10 days of intensive insulin treatment (T(2)D+; plasma glucose 5.5 +/- 0.2 mmol/l). Plasma proteins were separated using single and two-dimensional gel electrophoresis. Western blot analysis was performed, and several proteins, which reacted with the Amadori-antibody (1-deoxyfructosyl lysine), were identified by tandem mass spectrometry. No significant differences in the glycation of proteins between the obese and lean groups were noted, but type 2 diabetic patients had several proteins with higher glycation than the control groups. We identified 12 plasma proteins with reduced reaction to the anti-Amadori antibody upon intensive insulin treatment. A significant (P < 0.03) difference in Amadori modification was observed between the T(2)D- and control subjects for all these proteins except the Ig light chain. Insulin treatment reduced Amadori modification of albumin (23.2%, P < 0.02), fibrin (34.6%, P < 0.001), Ig heavy chain constant region (20.7%, P < 0.05), transferrin (25.4%, P < 0.04), and Ig light chain (13%, P < 0.02). In addition, Western blot analysis of two-dimensional gel electrophoresis identified alpha-fibrinogen precursor, beta-fibrinogen precursor, fibrinogen gamma-B chain precursor, hemopexin, vitamin D binding protein, and serine protease inhibitor as proteins with a reduced reaction to anti-Amadori antibody upon intensive insulin treatment. The current approach offers the opportunity to identify Amadori modification of many proteins that may cause functional alterations and offers the potential for monitoring short-term glycemic control in diabetic patients.

Insulin infusion normalizes fasting and post-prandial albumin and fibrinogen synthesis in Type 1 diabetes mellitus.

The effect of metabolic control on hepatic synthesis of plasma proteins in Type 1 diabetes mellitus (T1DM), in the post-absorptive and post-prandial state, is not known. We measured fractional synthetic rates (FSR) of albumin and fibrinogen in six insulin-infused T1DM patients and in five to nine control subjects, before and for approx. 4 h after a mixed liquid meal. Phenylalanine tracer precursor/product relationships and steady-state conditions were used. In the post-absorptive state, patients were studied in near euglycaemic conditions after an overnight intravenous insulin infusion. During the meal (approx. 11 kcal/kg), the insulin infusion rate was increased to maintain plasma glucose concentrations below approx. 10 mmol/l. Post-absorptive FSR of albumin (5.7 +/- 0.6%/day) and fibrinogen (11.3 +/- 0.6%/day) in T1DM were similar to control values (6.4 +/- 0.9 and 13.1 +/- 1.1, respectively). After the meal, albumin FSR increased (P = 0.0032 by anova) in both groups (T1DM, to 14.4 +/- 2.7%/day; controls, to 18.2 +/- 3.7%/day). Fibrinogen FSR also increased (P = 0.0048 by anova) in both the T1DM (to 18.2 +/- 2.6) and the control subjects (to 27.3 +/- 6.2). There was no difference between T1DM and control subjects in the post-prandial FSR of both proteins. Albumin and fibrinogen FSR in T1DM can be maintained within near-normal ranges by insulin infusion under post-absorptive and post-prandial conditions.

Levels of carbonyl groups in plasma proteins of type 2 diabetes mellitus subjects

Carbonyl groups result from protein oxidation and their level in tissues and plasma is a relatively stable marker of oxidative damage. Carbonyl content of plasma proteins in 43 type 2 diabetic subjects, 30-87 years of age (25 males and 18 females) and in 20 age-matched healthy controls (31-89 years of age, 12 males and 8 females) was evaluated with 2,4-dinitro-phenyl-hydrazine method. In both groups, lipids, tocopherols (HPLC) and glycated hemoglobin (HPLC) were studied. Fasting blood glucose, glycated hemoglobin and lipids were significantly higher in the diabetic group; carbonyl content and alpha-tocopherol were slightly, but not significantly higher in the diabetic group (1.06 +/- 0.03 vs. 0.97 +/- 0.04 nmol/mg protein, 27. 07 +/- 2.82 vs. 31.55 +/- 2.11 micromol/l, respectively). Significant relationships between age and lipids, alpha-tocopherol and proteins were found in controls, but not in diabetics. Alpha-tocopherol correlated with lipids in both groups; glycated hemoglobin, a marker of glycemic control, was related to lipids, alpha-tocopherol and protein carbonyl groups in diabetics, while only the correlation with carbonyls was found in controls. These results suggest that impaired glycemic control is connected to protein oxidation. Glycation cascade also releases free radicals, becoming responsible for further oxidative attacks. In conclusion, increased oxidative stress, if any, in the diabetic group, is doubtlessly induced by hyperglycemia, and the tocopherols are not seriously affected by a worsening of the metabolic control.