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)

Urine albumin (Alb), total protein (TP) and creatinine (Cr) concentrations and the activities of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP) and gamma-glutamyl transpeptidase (GGT) were measured in untimed random urine samples from 157 non-insulin-dependent (NIDDM) diabetic subjects and 54 healthy subjects. In NIDDM subjects the excretions of TP, Alb, NAG, AAP, GGT (expressed in relation to creatinine) were significantly higher and were abnormal in 59.9%, 68.8%, 47.2%, 41.4% and 13.4% of the subjects, respectively. However, 24.5%, 22.4% and 6.1% of NIDDM subjects with normal Alb/Cr ratio had abnormal excretion of NAG, AAP and GGT, respectively. Alb/Cr ratio was greater than 26.8 mg/mmol (considered to be equivalent to albumin excretion of 250 mg/24 h) in 14.6% and between 2.5-26.8 mg/mmol (equivalent to albumin excretion rates of 20-250 mg/24 h) in 54.1% of subjects. In those diabetic subjects with clinical retinopathy only Alb/Cr ratio was higher. Arterial blood pressure was significantly correlated with Alb/Cr (r = 0.365) and NAG/Cr (r = 0.204). We conclude that prevalence of abnormal Alb/Cr is relatively common among Chinese NIDDM subjects.
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PMID:Urinary excretion of albumin and enzymes in non-insulin-dependent Chinese diabetics. 197 40

The activity and intracellular localization of two B-glycosidases i.e., N-acetyl-beta-D-glucosaminidase (NAG) and beta-glucuronidase (GR) was estimated by means of semi-quantitative histochemical methods in the peripheral blood neutrophils and lymphocytes from 52 patients with non-insulin dependent diabetes mellitus and compared with that in 67 healthy subjects of similar age and sex. The total neutrophil and lymphocyte count did not differ in the patients from that in the controls. The GR and the NAG activity indexes were significantly lower in the neutrophils from patients as compared with that in the control group. The number of lymphocytes with GR-positive and NAG-positive intact lysosomes were 200-fold and respectively 40-fold lower in the patients than in the healthy subjects. The authors discuss the significance of their observations with regard to the relationship between the enzymatic activity of the cells studied and their functional capabilities.
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PMID:The deficiency of B-glycosidases in leukocytes from patients with non-insulin dependent diabetes mellitus. 408

Urine albumin, alpha 1- and beta 2-microglobulins, retinol-binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) were measured in early morning urine samples from 99 non-insulin-dependent diabetic (NIDDM) patients receiving ambulatory care at a primary health care polyclinic. Elevated NAG levels were found in 90% of diabetics regardless of the duration of their disease. Almost half (43.4%) of the subjects had microalbuminuria. Over a third of the subjects without albuminuria had elevated alpha 1-microglobulin levels in their urine. The proportion of subjects with elevated alpha 1 levels increased significantly with the presence of albumin, poor glycaemic control and increased duration of disease. These findings suggest that proximal tubular as well glomerular dysfunction coexist in the NIDDM patients studied.
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PMID:Proteinuria and enzymuria in non-insulin-dependent diabetics. 769 91

Insulin resistance and hyperinsulinemia cluster with microalbuminuria in both diabetic and nondiabetic subjects, but the mechanism underlying this association is unknown. To test the hypothesis that insulin influences protein permeability, we measured the albumin transcapillary escape rate (TER) by the (131)I-labeled albumin technique in 12 healthy volunteers and 12 normoalbuminuric NIDDM patients (fasting plasma glucose, 10.9 +/- 1.3 mmol/l) during 4 h of isoglycemia with high (1.1 mU x min(-1) x kg(-1)) or, on a different day, low (0.1 mU x min(-1) x kg(-1)) insulin infusion. In both patients and control subjects, high insulin was associated with a 7% decrease in blood volume (P = 0.006) and a 6% decrease in diastolic blood pressure (P < 0.02), these two changes being related to one another (r = 0.56, P < 0.01). Basal albumin TER was similar in patients (8.4 +/- 0.5% x h(-1)) and control subjects (7.7 +/- 0.7% x h(-1)) and was not significantly changed by high insulin in either group (patients vs. control subjects, 7.3 +/- 0.9 vs. 6.2 +/- 0.4% x h(-1); NS vs. low insulin). In contrast, high insulin increased renal albumin excretion (from 3.6 +/- 0.8 to 5.4 +/- 1.1 microg/min, P < 0.01) and clearance rate (0.09 +/- 0.02 to 0.13 +/- 0.03 microl/min, P < 0.001) in patients but not in control subjects. To localize the effect of insulin along the nephron, we measured the urinary excretion of N-acetyl-beta-D-glucosaminidase (beta-NAG), released by the proximal tubule; retinol-binding protein (RBP), reabsorbed by the proximal tubule; and Tamm-Horsfall protein (THP) and epidermal growth factor (EGF), both secreted by the distal tubule. For both beta-NAG and RBP, but not EGF or THP, insulin enhanced urinary excretion (diabetics vs. controls: beta-NAG, 0.48 vs. -0.15 microU/min [P = 0.03]; RBP, 78 vs. -32 ng/min [P = 0.05]). In conclusion, physiological hyperinsulinemia does not affect systemic albumin permeability in healthy subjects or normoalbuminuric NIDDM patients. In contrast, in NIDDM patients, but not in healthy subjects, insulin increases the urinary excretion of albumin and protein markers of proximal tubular function. The significance of this finding for the pathogenesis of diabetic nephropathy remains to be established.
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PMID:Effect of insulin on systemic and renal handling of albumin in nondiabetic and NIDDM subjects. 913 57

The activity of the isoenzymes of N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) is determined in the serum of insulin-dependent (IDDM) and non-insulin-dependent diabetics (NIDDM) with or without diabetic complications. The increase in total activity of serum NAG in diabetics is proportional to the A form activity (r = 0.976, p < 0.0001). The contribution of the A form activity (65.87 +/- 5.99%) to total NAG activity of IDDM and NIDDM diabetics with and without complications does not change considerably compared to the control group. The contribution of the B form activity depends on the state of metabolic monitoring and diabetic complications. A significantly lower activity of the serum B form was found in IDDM (p < 0.001) and NIDDM diabetics (p < 0.05) compared to the healthy individuals, as well as the higher activity ratios of the A/B forms. A decrease in serum B form is correlated with the occurrence and abundance of the intermediary I forms (r = 0.665). These changes are particularly significant in the individuals with the pronounced microangiopathy.
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PMID:Changes of isoenzymes of serum N-acetyl-beta-D-glucosaminidase in relation to different types of diabetes. 967 55

The erythrocyte membrane in 71 patients with type 2 diabetes mellitus was assessed for glycohydrolase activity: N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, alpha- and beta-D-galactosidase, alpha- and beta-D-glucosidase, alpha-D-mannosidase, and alpha-L-fucosidase. Only beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase showed markedly elevated levels with respect to the controls regardless of the presence of complications. Among the examined patients, those with good metabolic control (not yet submitted to any therapy) showed the same enzyme levels as the reference subjects, while the levels in patients with unsatisfactory metabolic control (treated with oral hypoglycemic and/or insulin) significantly differed from the control levels. For alpha-D-glucosidase and beta-glucosidase, a correlation with glycemia and the parameters of metabolic control was also evidenced. Alterations of beta-D-glucuronidase, alpha-D-glucosidase, and beta-D-glucosidase were also ascertained in the plasma of the same diabetic patients according to the literature; each enzyme correlated with the other, either in plasma or in the erythrocyte membrane. This study shows a correlation between plasma and erythrocyte membrane levels for these three enzymes. The strict parallelism of the glycohydrolases in the two different compartments provides a profile of these enzymes in the pathology of diabetes.
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PMID:Alterations in the activity of several glycohydrolases in red blood cell membrane from type 2 diabetes mellitus patients. 1042 Dec 18

This study examined the association between urinary markers of early diabetic nephropathy and non-renal diabetic complications in 946 patients with type 2 diabetes mellitus. The association with hypertension was also studied. Data on macrovascular complications (ischaemic heart disease, stroke, peripheral vascular disease) and microvascular complications (retinopathy, peripheral neuropathy) were obtained from case records and clinical examination. Urine samples collected were analysed for albumin, beta(2)-microglobulin, retinol-binding protein (RBP), and N-acetyl-beta-D-glucosaminidase (NAG). Results showed that urinary albumin, RBP and beta(2)-microglobulin levels were higher in patients with macro- and/or microvascular complications, compared to those without. NAG levels were higher only in patients with both types of complications. A higher proportion of patients with complications had abnormally raised urinary protein and enzyme levels, compared to those without. Patients with associated hypertension had higher urinary levels of albumin and beta(2)-microglobulin, regardless of whether complications were present or not. RBP excretion was, however, markedly higher only in patients with microvascular complications, whereas hypertension did not influence NAG excretion. Urine albumin and RBP excretion were predictive of microvascular, as well as both macrovascular and microvascular complications, whereas NAG excretion was predictive of macro- and microvascular complications. These findings could mean that increased urinary protein and enzyme excretion were associated with more severe disease in these patients.
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PMID:Urinary protein excretion in Type 2 diabetes with complications. 1111 88

Although only recently described, the pathway of O-linked protein glycosylation is already being implicated in diseases as diverse as cancer and Alzheimer's. Unlike the better known N-linked pathway, O-linked protein glycosylation is a dynamic and regulated event, much like tyrosine phosphorylation. During the process of O-glycosylation, the enzyme O-GlcNAc transferase (OGT) uses the substrate UDP-N-acetylglucosamine (UDP-GlcNAc) to attach a single O-linked N-acetylglucosamine (O-GlcNAc) to nuclear and cytosolic proteins on serine or threonine residues. Conversely, the enzyme O-GlcNAc-selective N-acetyl-beta-D-glucosaminidase (O-GlcNAcase) removes the O-GlcNAc, returning the protein to its baseline state until the cycle repeats itself. Although proving to be of interest in many different tissues, this pathway is especially important in pancreatic beta-cells. The beta-cell is unique in containing much more OGT than any other cell type. This enables beta-cells to respond to physiological increases in the glucose concentration by converting glucose to the OGT substrate UDP-GlcNAc, thereby dynamically coupling intracellular O-linked protein glycosylation to the extracellular glucose concentration. As a result, the beta-cell also appears to be especially susceptible to disruption of the O-glycosylation pathway. The diabetogenic agent streptozotocin (STZ), a UDP-GlcNAc analogue, causes beta-cell toxicity by irreversibly inhibiting O-GlcNAcase, while the diabetogenic agent alloxan (ALX), also a UDP-GlcNAc analog irreversibly inhibits OGT. This review will summarize what is currently known about beta-cell O-glycosylation and expand upon historical observations of chemically-induced beta-cell toxicity in animals to develop a model suggesting how beta-cell O-glycosylation is also involved in the development and progression of type 2 diabetes in humans.
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PMID:The role of O-linked protein glycosylation in beta-cell dysfunction. 1237 87

Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the mechanisms for the development and progression of diabetic nephropathy are not fully understood, platelet activation may participate in its pathogenesis by promoting microthrombus formation. In this study, we investigated the effects of dilazep hydrochloride, an antiplatelet agent, on the development and progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a type 2 diabetes mellitus animal model. Administration of dilazep hydrochloride significantly reduced the increase of urinary protein excretions and N-acetyl-beta-D-glucosaminidase (NAG) activity in OLETF rats. Furthermore, dilazep hydrochloride treatment prevented glomerulosclerosis and tubular atrophy and reduced positive staining for type IV collagen in the glomeruli of diabetic rats. These results indicate that platelet activation plays a dominant role in the development and progression of diabetic nephropathy. Our study suggests that dilazep hydrochloride is a valuable new drug for the treatment of diabetic patients with nephropathy.
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PMID:Dilazep hydrochloride, an antiplatelet drug, prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats. 1277 75

Disturbed metabolism of glycosaminoglycans (GAGs) has been proposed to play an important role in the pathogenesis of late diabetic complications. The effect of diabetic complications and metabolic control on both total serum GAGs content and the serum activity of lysosomal glycosidases (N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase, beta-D-galactosidase, and alpha-D-mannosidase) contributing to GAGs degradation, was investigated in 48 patients with type 2 diabetes mellitus. The activity of beta-D-glucosidase and acid phosphatase, the lysosomal enzymes unrelated to GAGs metabolism, was determined for comparison. The elevated serum total GAG concentration in diabetic patients was strongly and positively influenced by poor metabolic compensation of diabetes and the presence of vascular complications. A similar tendency has been shown in regard to the activity of enzymes involved in GAG degradation, especially N-acetyl-beta-D-glucosaminidase, alpha-L-fucosidase and beta-D-galactosidase. Furthermore, the total serum GAG concentrations, as well as the activity of lysosomal enzymes involved in the extracellular matrix degradation, closely followed metabolic compensation, regardless of diabetic vascular complications. Thus, we suggest that increased values of the investigated parameters may indicate the degree of endothelial cell dysfunction and may be useful to predict the development of diabetic vascular pathology.
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PMID:Alterations of glycosaminoglycan metabolism in the development of diabetic complications in relation to metabolic control. 1617 71


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