Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelet levels of 19 amino acids were measured in 20 outpatients with type 1 (age [mean +/- SE], 35.5 +/- 2.0 years) and 27 with type 2 (age, 58.4 +/- 1.4 years) diabetes, and 20 young (age 33.7 +/- 1.3 years) and 20 older (age 57.4 +/- 1.5 years) healthy volunteers. Platelet levels of most amino acids tended to be lower in patients with type 1 diabetes than in healthy controls. In particular, asparagine, glycine, taurine, alanine, valine, cysteine, leucine, phenylalanine, and lysine levels, expressed as nmol/10(8) platelets, were significantly lower. Only taurine significantly decreased in patients with type 2 diabetes, whereas threonine, alanine, and isoleucine increased.
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PMID:Preliminary report: Amino acid profile in platelets of diabetic patients. 1143 75

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.
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PMID:Increased levels of vascular endothelial growth factor and advanced glycation end products in aqueous humor of patients with diabetic retinopathy. 1144 Feb 80

Advanced glycation end products (AGEs) such as N(epsilon)-(carboxymethyl)lysine (CML) have been implicated in the development and progression of diabetic nephropathy. The aim of the present study is to investigate AGE levels in patients with type 2 diabetes with special regard to the role of renal impairment. Serum and urine CML levels (using a newly developed enzyme-linked immunosorbent assay), as well as serum AGE-fluorescence, were measured in 109 patients with type 2 diabetes. Patients were divided into groups with normal and impaired renal function. We found elevated serum fluorescent AGE and CML levels, as well as decreased urinary CML excretion rates, in patients with diabetes with renal impairment, but not those with normal renal function. In the presence of impaired renal function, serum CML and fluorescent AGE levels showed a significant inverse relation with creatinine clearance and a significant direct correlation with each other. No relationship could be found between serum AGE levels and parameters of blood glucose control or the presence of the following clinical complications: ischemic heart disease, diabetic retinopathy, and neuropathy. We conclude that the decline in renal function leads to increased serum AGE levels in patients with type 2 diabetes.
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PMID:N(epsilon)-(carboxymethyl)lysine levels in patients with type 2 diabetes: role of renal function. 1157 82

Atherosclerosis is remarkably increased in type 2 diabetes suggesting that mechanisms causing arterial lesion are enhanced by the metabolic disturbances of insulin resistance (IR) and diabetes. Several lines of research suggest that processes taking place in the arterial intima extracellular matrix may be part of a shared pathogenic mechanism. The intima extracellular matrix is where atherogenesis takes place. This layer contains fibrilar macromolecules like collagens, proteoglycans (PGs), hyaluronate, and extracellular multi-domain proteins. Specific interaction of lysine, arginine-rich segments of the apoB-100 lipoproteins, LDL, IDL and Lp (a), with the negatively charged glycosaminoglycans (GAGs) of PGs cause retention of the lipoproteins, one of the initiation process of atherogenesis. Such interactions cause structural modifications of the lipid and protein moieties of the lipoproteins that appear to increase their susceptibility to proteases, phospholipases and free radical-mediated processes. The association of apoB-lipoproteins, specially small and dense LDL, with intima PGs increases their uptake by macrophages and human arterial smooth muscle cells (HASMC) leading to 'foam cell' formation. In vitro, elevated levels of non-esterified fatty acids (NEFA) alter the matrix of endothelial cells basement membrane making them more permeable to macromolecules. NEFA cause changes in the expression of genes controlling the PGs composition of the PGs secreted by HASMC causing formation of a matrix with high affinity for LDL. These results lead us to speculate that an important component of the dyslipidemia of IR and type 2 diabetes, chronic high NEFA, may contribute to cellular alterations that cause changes of the arterial intima extracellular matrix. Such changes may increase the atherogenicity of the retention of apoB lipoproteins in the intima and contribute to the systemic alteration of the arterial wall frequently observed in IR and type 2 diabetes.
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PMID:The extracellular matrix on atherogenesis and diabetes-associated vascular disease. 1204 79

Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to type 2 diabetes mellitus (T2DM). For example, there is evidence suggesting that vitamin D binding protein (DBP) amino acid variants at codons 416 (aspartic acid-->glutamic acid) and 420 (threonine-->lysine) may affect genetic susceptibility to T2DM. The aims of this study are: (1) to determine the allele, genotype, haplotype and haplotype combination frequencies of those DBP amino acid variants in a Polish population and (2) to examine their role in the genetic susceptibility to T2DM in a Polish population. Overall 393 individuals were included in this study: 231 T2DM patients and 162 controls. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by specific restriction enzymes HaeIII and StyI. Since variants of DBP were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. Differences in distributions between the groups were examined by chi(2) test. At codon 416 the frequency of Asp/Glu alleles was 44.6/55.4% in T2DM patients and 40.7/59.3% in controls (chi(2)=2.1, d.f.=1, P=0.28). At codon 420 the frequency of Thr/Lys alleles were 69.4/30.6% and 71.6/28.4%, (chi(2)=0.41, d.f.=1, P=0.52), respectively. Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In conclusion, the frequency of amino acid variants at codons 416 and 420 of vitamin D binding protein gene in a Polish population is similar to other Caucasian populations, but differs significantly from other races. No evidence was found for an association between DBP frequent polymorphisms and T2DM in this population.
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PMID:Vitamin D binding protein gene and genetic susceptibility to type 2 diabetes mellitus in a Polish population. 1206 54

This study describes the occurrence of 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one (HMDP) in plasma obtained from normal subjects and patients with type 2 diabetes. We have shown previously that HMDP is a novel hydrophilic hydroperoxide formed in the in vitro Maillard reaction that could be analyzed using ultrasensitive chemiluminescence detection-high-performance liquid chromatography (CL-HPLC). The HMDP concentration was 273+/-227 nmol/l in normal subjects and 656+/-535 nmol/l in patients with diabetes. The HMDP concentration was proportional to the plasma glucose concentration level (r=0.640; P<0.01) but not with the glycated hemoglobin level. To investigate the in vivo effects of HMDP, a range of concentrations of the compound was incubated for different time periods with human serum albumin and lipoproteins. HMDP was found to induce denaturation of these macromolecules by modifying lysine residues and causing cross-linking and polymerization of proteins. In the presence of metal ions such as iron and copper, HMDP induced peroxidative degradation of lipoprotein lipids as measured by an elevation in thiobarbituric acid reactive substances (TBARS) concentration. These results suggested that HMDP is produced as a consequence of both hyperglycemia and increased oxidative stress, and may have the potential to contribute to the pathogenesis of arterial complications in diabetes mellitus.
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PMID:The occurrence of a novel hydrophilic hydroperoxide, 3-hydroxy-5-hydroperoxy-2-methyl-5,6-dihydropyran-4-one, as a reactive glycation product in human plasma. 1238 41

A time-delayed fluorescence immunoassay was developed for the determination of serum levels of methylglyoxal (MG)-derived hydroimidazolone using a monoclonal antiserum raised against Nalpha-acetyl-Ndelta-(5-hydro-5-methyl)-4-imidazolone, Europium-labeled anti-mouse IgG antiserum as indicator, and MG modified bovine serum albumin (BSA) as standard. Serum levels of hydroimidazolone were measured in 45 patients with type 2 diabetes aged 59.4 +/- 6.1 (mean +/- SD) years and with duration of diabetes of 7.3 +/- 3.1 years, and in 19 nondiabetic controls aged 56.3 +/- 4.3 years. The serum levels of hydroimidazolone were significantly higher in patients compared to controls: median, 3.0 (5-95 percentile, 1.6 to 5.4) U/mg protein versus 1.9 (1.2 to 2.8) U/mg protein (P =.0005). Significant positive correlations were observed between the serum levels of hydroimidazolone and serum levels of advanced glycation end products (AGEs), measured with a polyclonal anti-AGE antibody: r = 0.59 for patients (P <.0001), and r = 0.65 for controls (P =.002). Similarly, significant correlations were also found between serum levels of hydroimidazolone and N(epsilon)-(carboxymethyl)-lysine (CML): r = 0.36 in patients and r = 0.55 for controls (both P =.02). Serum hydroimidazolone levels did not correlate with fasting plasma glucose or hemoglobin A(1c) (HbA(1c)) levels. The observed differences between patients with diabetes and nondiabetic controls seem to be comparable to differences measured for other AGE compounds.
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PMID:Increased serum levels of the specific AGE-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes. 1260 26

The accumulation of Nxi-(carboxymethyl)lysine (CML), a product of glycoxidation and lipoxidation reactions, on tissue proteins is related to the formation and acceleration of diabetic and nondiabetic atherosclerotic lesions. Yet, little is known about the levels of circulating serum CML-containing protein in nondiabetic patients with clinical symptoms of advanced atherosclerosis. We measured the levels of immunoreactive CML in sera from non-diabetic patients with accelerated symptoms of coronary heart disease, from diabetic patients with no late complications, and from healthy individuals. Serum CML was significantly higher in non-diabetic patients with coronary heart disease than in healthy control subjects and was comparable to serum CML in patients with type 2 diabetes mellitus without late complications and coronary heart disease. In nondiabetic patients with coronary heart disease, a significant inverse correlation was found between serum levels of CML and proinsulin C-peptide, a marker of pancreatic beta cells activity that affects microvascular function. Serum levels of CML and high density lipoprotein (HDL) were positively correlated in this group. We conclude that glycoxidation and lipoxidation are associated with serum HDL levels and the secretive capacity of pancreatic beta cells in nondiabetic patients with coronary heart disease.
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PMID:Serum N-epsilon-(carboxymethyl)lysine is elevated in nondiabetic coronary heart disease patients. 1267 29

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus, but it is also present in up to 25% of healthy nonobese individuals. The molecular mechanisms causing insulin resistance are not yet fully understood. Recently, overexpression of several potential inhibitors of the insulin receptor tyrosine-kinase activity, a key step in insulin signaling, has been described in insulin-resistant subjects . PC-1 is expressed in many tissues and inhibits insulin signaling either at the level of the insulin receptor or downstream at a postreceptor site. An elevated PC-1 content in insulin target tissues may play an important role in the development of insulin resistance in obesity and type 2 diabetes mellitus. A polymorphism in PC-1 has been demonstrated to be associated with insulin resistance. This was a DNA polymorphism in exon 4 that causes an amino acid change from lysine to glutamine at codon 121 (K121Q). PC-1 121Q allele might predispose independently of other well established risk factors for early myocardial infarction. Testing for the PC-1 K121Q polymorphism might be valuable in patients with a family history of atherosclerotic vascular disease and myocardial infarction. There is growing evidence that genetic factors play an important role in the development of diabetic nephropathy (DN). Efforts to identify these factors rely primarily on the candidate gene approach; candidate genes for insulin resistance may be considered candidates for DN as well. In a stratified analysis according to duration of diabetes, the risk of early-onset end-stage renal disease (ESRD) for carriers of the Q variant was 2.3 times that for noncarriers. The cellular mechanisms for the insulin resistance of pregnancy and gestational diabetes mellitus (GDM) are unknown. Women with GDM have an increased PC-1 content and excessive phosphorylation of serine/threonine residues in muscle insulin receptors. The postreceptor defects in insulin signaling may contribute to the pathogenesis of GDM and the increased risk for type 2 diabetes later in life. Although widely explored, the true cause of insulin resistance in uremic patients is not entirely elucidated yet. During the last decade it was found that erythropoietin (EPO) therapy, used for correction of anemia in patients with end stage renal failure, ameliorates insulin resistance. An increased lymphocyte PC-1 activity over control was found in hemodialysis patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uremic patients treated with EPO. Current investigations implicate that therapeutic modification of PC-1 expression would be of great benefit for insulin-resistant type 2 diabetics. Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics. Thiazolidinedione (TZD) insulin-sensitizing drugs are a class of compounds that improve insulin action in vivo. Treatment of patients with TZDs seems to have a beneficial effect on most, if not all, components of metabolic syndrome. TZDs have also been used in the treatment of nondiabetic human insulin-resistant states, and have demonstrated an improvement in insulin sensitivity. Although much remains to be learned about PPAR gamma receptor and TZD action, the advent of TZD insulin-sensitizing agents has an enormous impact on our understanding of insulin resistance. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms.
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PMID:Plasma cell membrane glycoprotein 1 (PC-1): a marker of insulin resistance in obesity, uremia and diabetes mellitus. 1520 35

Soy protein was shown to exhibit several beneficial effects on renal function in nondiabetic patients with nephropathy, and to improve serum lipids. This study examined the effects of isolated soy protein consumption on urinary albumin excretion, serum lipids, plasma amino acids, and isoflavones in diabetic patients with nephropathy. Male patients (n = 14) with type 2 diabetes and nephropathy were followed in a crossover design for 7 mo. The study comprised two 8-wk intervention periods, placed between a 4-wk lead-in and two 4-wk washout periods. In the 2 intervention periods, 0.5 g/(kg. d) of the dietary protein was provided as either isolated soy protein (ISP) or casein, in random order. Blood and urine samples were collected at the beginning and end of each period. Data were analyzed by multiple linear regression for a repeated-measure design. ISP consumption led to changes of -9.5% in urinary albumin excretion (P < 0.0001), -0.45 in the total-to-HDL-cholesterol ratio (P < 0.05), -0.20 in the LDL-to-HDL cholesterol ratio (P < 0.05), and +4.3% in HDL cholesterol (P = 0.0040). Plasma arginine concentrations, the arginine-to-lysine ratio, and plasma isoflavone concentrations were higher after ISP consumption (P < 0.05). Urinary albumin excretion was negatively correlated with plasma total isoflavones (rho = -0.441), daidzein (rho = -0.326), and O-desmethylangolesin (rho = -0.389) (P < 0.05). The findings indicate that isolated soy protein consumption improves several markers that may be beneficial for type 2 diabetic patients with nephropathy.
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PMID:Isolated soy protein consumption reduces urinary albumin excretion and improves the serum lipid profile in men with type 2 diabetes mellitus and nephropathy. 1528 69


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