Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pseudotetrasaccharide acarbose, previously known as a potent inhibitor of intestinal alpha-glucoside hydrolases, was investigated with regard to its influence on islet lysosomal enzyme activities and the insulin secretory processes. We observed that acarbose was a potent inhibitor of mouse islet lysosomal acid glucan-1,4-alpha-glucosidase activity, EC50 approximately 5 mumol/l, as well as of acid alpha-glucosidase activity. In contrast, acarbose did not influence other lysosomal enzyme activities such as acid phosphatase and N-acetyl-beta-D-glucosaminidase. Neutral alpha-glucosidase (endoplasmic reticulum) was only moderately inhibited in homogenate and was unaffected in intact islets. Incubation of isolated mouse islets with acarbose revealed that the pseudotetrasaccharide was a strong inhibitor of glucose-induced insulin secretion, EC50 approximately 500 nmol/l, and a significant inhibition was already observed at a concentration of acarbose as low as 100 nmol/l. The acarbose analogue maltotetrose did not influence either glucose-induced insulin release or islet lysosomal enzyme activities. Further, acarbose as well as two other alpha-glucoside hydrolase inhibitors, the deoxynojirimycin derivatives miglitol and emiglitate, did not affect islet glucose oxidation at low or high glucose levels. Acarbose also inhibited insulin release induced by the sulfonylurea glibenclamide, whereas insulin secretion stimulated by the cholinergic muscarinic agonist carbachol or the phosphodiesterase inhibitor isobutylmethylxanthine was unaffected by the drug. Moreover, complementary in vivo experiments showed that pretreatment of mice with acarbose to allow for endocytosis of the compound markedly suppressed the insulin secretory response to an intravenous glucose load.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1995 Jul
PMID:The pseudotetrasaccharide acarbose inhibits pancreatic islet glucan-1,4-alpha-glucosidase activity in parallel with a suppressive action on glucose-induced insulin release. 778 51

Experimental work in our laboratory has confirmed the protective activity of vanadium compounds on hyperglycemia and glycosuria in streptozotocin (STZ) diabetes. Furthermore, diabetic cataract has also been partially prevented. Nevertheless, the combination of a natural antioxidant, vitamin E, with Na3 VO4 has not further enhanced this ameliorating effect. Our experimental approach has been an attempt to block the prooxidant activity of both STZ and vanadate, with the purpose of eliciting the best possible antidiabetic protection. More recently, a lipid soluble synthetic antioxidant U-78517F, a 2-methylaminochroman, has been reported to have a significant protective effect against brain injury and ischemia. This compound inhibits the iron-dependent lipid peroxidation 100 times more effectively than vitamin E. This investigation has introduced a combination of the vanadium compound plus the aforesaid lazaroid, as its (-) enantiomer, U-83836E, in order to improve the insufficient protection when vitamin E was used. For twelve weeks, male Wistar rats, rendered diabetic with STZ, were administered Na3VO4 in drinking water along with the lazaroid carried by the food. Four, eight and twelve weeks after the beginning of the protective treatment, fluid and food intake, diuresis and excreted feces, glycosuria and proteinuria were determined on biological samples obtained in metabolic cages; body weight and glycemia were also recorded. At weeks 6 and 12 of the treatment, the opaqueness of the eye lenses was controlled and registered. At the end of the experiment, circulating glycosylated hemoglobin (HbA1c), fructosamine, N-acetyl-beta-D-glucosaminidase (NAG), and fluorescent peroxides were evaluated. Within the first month of treatment, protection by the combination paralleled that elicited by vanadate alone. At subsequent steps, U-83836E significantly improved the protective effect of vanadate alone on polydipsia and polyuria, but especially on hyperglycemia and glycosuria. The further ameliorating effect of the lazaroid was also observed on HbA1c and NAG, and, most important, on the cataract. In conclusion, these findings demonstrate that the lazaroid U-83836E succeeds in further protecting the most important symptoms of diabetes treated with vanadate, and that this antioxidant acts effectively even when it is administered orally in food, in a non invasive manner.
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PMID:Amelioration of diabetes and cataract by Na3VO4 plus U-83836E in streptozotocin treated rats. 782 6

Urinary levels of glycosaminoglycans (U-GAG) were measured in 72 patients with non-insulin-dependent diabetes mellitus, 12 patients with collagen diseases, 14 patients with IgA nephropathy and 35 healthy subjects as controls to investigate the clinical significance of urinary GAG. The mean urinary GAG levels in diabetics and patients with collagen diseases were 72.4 +/- 36.2 and 147.8 +/- 59.2 mg/g.cr, respectively. These were significantly higher than the level in healthy subjects (46.7 +/- 11.3 mg/g.cr, p < 0.01). The mean urinary GAG level in patients with IgA nephropathy was 56.4 +/- 21.0 mg/g.cr and did not differ from that in healthy subjects. The mean urinary GAG level in 35 normoalbuminuric diabetic patients (U-A1b < 30 mg/g.cr) was 64.4 +/- 25.6 mg/g.cr and was significantly higher than that in healthy subjects (p < 0.01). The mean urinary GAG levels in 24 microalbuminuric patients (30 < U-A1b < or = 300 mg/g.cr) and 13 patients with overt albuminuria (U-Alb > or = 300 mg/g.cr) were 71.4 +/- 30.1 and 95.8 +/- 58.4 mg/g.cr, respectively and were also higher than the level in healthy subjects (both p < 0.01). Urinary GAG levels correlated positively with urinary albumin levels (r = 0.251, p < 0.05) and urinary N-acetyl-beta-D-glucosaminidase activities in diabetics (r = 0.491, p < 0.01). The prevalence of diabetic macroangiopathies in diabetic patients with elevated levels of urinary GAG was significantly higher than that in those with normal levels of urinary GAG (p < 0.05).
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PMID:[Urinary glycosaminoglycans in patients with non-insulin-dependent diabetes mellitus, collagen diseases and IgA nephropathy]. 813 46

A prospective open clinical trial was carried out with 23 hypertensive type I diabetics (13 men, ten women, mean age 49 +/- 9.1 years, duration of diabetes 18 +/- 9.1 years) with early nephropathy. Glomerular and tubular renal function and metabolic parameters were monitored during 8 months' treatment with the angiotensin converting enzyme (ACE) inhibitor, captopril, in addition to previous antihypertensive treatment with one or more drugs. Blood pressure control tended to improve on captopril (systolic pressures 152 +/- 13 vs 140 +/- 13 mm Hg, P < 0.05; diastolic pressures 89 +/- 10 vs 87 +/- 10 mm Hg, not significant). Proteinuria (> 0.5 g/24 hours) fell into the microalbuminuria range (albumin excretion 2-20 mg/mmol creatinine) in four out of 13 patients, and microalbuminuria disappeared in four out of ten patients. Urinary levels of the brush border enzyme N-acetyl-beta-D-glucosaminidase (NAG), a marker of tubular dysfunction, were initially raised and fell significantly after 8 months' treatment with captopril (20.3 +/- 14.4 vs 8.8 +/- 8.1 U/g creatinine; P < 0.01). Captopril did not affect metabolic control (HbA1, total, HDL and LDL cholesterol, triglycerides, apolipoproteins A1 and B) or the insulin dosage. These results show that long-term treatment with captopril may favourably influence both albumin excretion and NAG activity, a marker of tubular dysfunction, in type I diabetics with nephropathy.
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PMID:[The effect of blood pressure-reducing therapy with captopril on tubular marker excretion in type-1 diabetics with nephropathy]. 820 41

Seventy-two diabetic (38 males) and 86 normal (41 males) children provided timed overnight urine collections. Fourteen of the diabetic and 33 of the normal children had concurrent overnight plasma insulin profiles. Urinary insulin clearance in the diabetic subjects was compared with excretion of albumin, growth hormone, retinol-binding protein, and N-acetyl-beta-D-glucosaminidase. In the normal subjects, urinary insulin excretion correlated with mean overnight plasma levels in the boys (r = 0.82, p < 0.001) but not in the girls (r = 0.32), and varied with puberty stage in the boys. Insulin clearance was greater in boys than girls during puberty, and fell in both sexes with advancing puberty. Insulin excretion was greater in diabetic than normal children in both sexes at all puberty stages. Insulin clearance was also greater in diabetic than normal subjects (1.05 +/- 0.1 ml min-1 1.73 m-2 vs 0.48 +/- 0.05 ml min-1 1.73 m-2, p < 0.001). Insulin excretion as a percentage of the filtered load was also greater in diabetic than normal subjects (1.9 +/- 0.27% vs 0.85 +/- 0.09%, p < 0.01). In the diabetic children, there was a correlation between urinary insulin and growth hormone excretion (r = 0.52, p < 0.02), and retinol-binding protein in those (n = 10) with higher retinol binding protein excretion (r = 0.76, p = 0.01). The value of urinary insulin excretion as a measure of free plasma insulin levels in normal and diabetic children may be limited by sex differences in renal insulin clearance, and by proximal renal tubular dysfunction in children with diabetes.
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PMID:Urinary excretion and clearance of insulin in diabetic and normal children and adolescents. 826 51

Different surveys have been carried out on the plasma activities of different glycosidases in patients with insulin-dependent diabetes mellitus, but research on urinary glycosidases in this disease is scanty and incomplete. To elucidate the behavior of these lysosomal enzymes in the metabolic alterations occurring in the glomerular basal membrane during the initial stages of diabetic nephropathy, we conducted a prospective study to examine the urinary activities of N-acetyl-beta-D-glucosaminidase (NAG), alpha-D-mannosidase, alpha- and beta-D-glucosidase, alpha-L- and beta-D-fucosidase, and beta-D-galactosidase in patients with type I insulin-dependent diabetes mellitus, surveyed over 18 months, whose early diabetic nephropathy was detected by the presence of microalbuminuria. The simultaneous determination of beta 2-microglobulin in urine confirmed the glomerular origin of the albuminuria. No statistically significant correlation was found between the levels of albuminuria and the activities of any of the glycosidases analyzed. In the diabetic patients, a significant decrease was observed in the activities of all the enzymes (p < 0.05), except NAG and alpha-D-mannosidase, although the decrease in the latter was very close to statistical significance (p = 0.028, unilateral; p = 0.057 bilateral). Similarly, in the patients, there was a significant negative correlation (p < 0.05) with the serum levels of fructosamine, except with beta-D-galactosidase, which showed a positive correlation (p < 0.05) with fructosamine and blood HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS)
J Diabetes Complications
PMID:Prospective study of the enzymatic activities in urine of N-acetyl-beta-D-glucosaminidase, alpha-D-mannosidase, alpha- and beta-D-glucosidases, alpha-L- and beta-D-fucosidases, and beta-D-galactosidase in type I diabetes mellitus with early nephropathy. 834 14

Urinary excretion of five low molecular weight proteins (LMWP) [beta 2-microglobulin (beta 2m), cystatin C (cyst C), Clara cell protein (CC16), retinol-binding protein (RBP) and alpha 1-microglobulin (alpha 1m)], albumin and N-acetyl-beta-D-glucosaminidase (NAG) were quantified in 16 patients who followed a weight reduction program which included Chinese herbs, which have been incriminated in the genesis of Chinese herbs nephropathy (CHN). An additional group of four patients transplanted for CHN were investigated. Urinary data were obtained for comparison purpose in five groups of proteinuric patients: two groups with normal serum creatinine (SCr) and glomerular albuminura [12 patients with diabetes mellitus and microalbuminuria (DN), 10 patients with primary nephrotic syndrome (NS)]; two groups with normal SCr and toxic nephropathy [6 patients with analgesic (AN), 9 patients with cadmium nephropathy (CdN)]; and one group of seven patients with glomerular diseases and increased SCr (GN). Patients were classified according to serum level S beta 2m to take into account the possibility of overflow proteinuria at S beta 2m > or = 5 mg/liter. Three patients (CHN0) with a S beta 2m < 5 mg/liter, had a normal urinary protein pattern including NAG and a normal S beta 2m. Eight patients (CHN1) with a S beta 2m < 5 mg/liter had various abnormalities of their urinary protein pattern. In four of them (CHN1a) only beta 2m, RBP and CC16 were increased while total proteinuria and SCr were normal. In the other four (CHN1b and c) albumin, cyst C, alpha 1m and NAG were also elevated, while total proteinuria and SCr were moderately raised. Five patients (CHN2) with a S beta 2m > or = 5 mg/liter had a markedly increased excretion of all LMWP, albumin and NAG (CHN1 vs. CHN2, P < 0.05) as well as a further increase in total proteinuria and SCr. The urinary LMWP/albumin concentration ratio was strikingly higher in CHN patients than in patients with glomerular albuminuria (CHN1 vs. DN and NS, P < 0.01) or moderate renal failure with elevated S beta 2m level (CHN2 vs. GN, P < 0.01), confirming the existence of a tubular proteinuria independent of glomerular albuminuria or overflow proteinuria. A similar proteinuria pattern was present in the two toxic nephropathies (CdN and AN). This pattern was no longer recognizable after transplantation. In conclusion, CHN exhibits various profiles of tubular proteinuria which are the hallmarks of the disease. This pattern is still detectable in patients with renal failure and/or glomerular albuminuria. It is identical to that observed in cadmium and analgesic nephropathies. It does not recur after transplantation. Its most sensitive and reliable marker is a raised urinary level of CC16 or RBP.
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PMID:Low molecular weight proteinuria in Chinese herbs nephropathy. 854 16

In an in-depth examination to better define the renal effects of mild hypertension, we used urinary proteins to indicate damage to the glomerulus (albumin), tubular reabsorption capability (retinol-binding protein), and turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) in a group of 18 people with mild hypertension not associated with diabetes and a control group (n = 12). The participants' activity was controlled on a high normal salt diet for 3 days followed by a low salt diet for 4 days. Two distinct patterns of albumin excretion were evident in the hypertensive group: 22% had elevated, highly variable excretion patterns, and the rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or 16 mg/L, with the lowest within-person biological variability given by albumin calculated as a ratio to creatinine. Albumin and NAG excretion primarily correlated with systolic blood pressure and the best correlations were given by ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8 mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg), diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group with mild hypertension. However, albumin excretion did not decrease when dietary salt content was lowered. The group with hypertension also had higher urinary excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in the group had a higher excretion of retinol-binding protein than did whites in the control group (P < .02). Retinol-binding protein values, however, were within the normal range, indicating that the elevated albumin values were the result of changes in selectivity of the glomerulus.
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PMID:An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension. 855 30

We evaluated the diagnostic utility of urinary transferrin (Tf) in patients with diabetic nephropathy by comparing the diagnostic findings with those of clinical stage and renal biopsy specimens. According to the rate of urinary albumin excretion, a total of 60 patients with non-insulin-dependent diabetes mellitus were separated into normoalbuminuria (< 28.8 mg/day), microalbuminuria (28.8 approximately 288 mg/day), and overt proteinuria (> 288 mg/day). They were also divided into 5 groups, D0, DI, DII, DIII and DIV according to the severity of glomerular diffuse lesions using Gellman's criteria. Thirty-eight non-diabetic volunteers were used as controls. Using 24-hour urine specimens, Tf was measured by latex-immuno-turbidimetry. Urinary concentrations of albumin, alpha 1-microglobulin, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) were also evaluated. Urinary Tf was significantly increased in the diabetic patients relative to the non-diabetic controls. The incidence of microtransferrinuria (440 approximately 4,400 micrograms/day) was 33.3% in normoalbuminuria, 63.2% in microalbuminuria, and 18.2% in overt proteinuria. The incidence of overt transferrinuria (> 4,400 micrograms/day) was 0%, 36.8% and 81.8%, respectively. Among the diabetic patients, urinary Tf showed a significant increase with respect to the progress of glomerular diffuse lesions. The glomerular diffuse lesions of 10 normoalbuminuric cases with microtransferrinuria were graded as DI in 8 cases, DII in 1 case, and DIII in 1 case. There was a significant correlation between the urinary excretion of Tf and that of albumin, alpha 1-microglobulin or NAG. The findings indicate that urinary Tf may be useful in detecting diabetic nephropathy at an early stage.
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PMID:Diagnostic significance of urinary transferrin in diabetic nephropathy. 858 2

To clarify the diagnostic relevance of urinary type IV collagen (IV-C) and laminin in diabetic nephropathy, the excretion of these basement membrane proteins were determined by enzyme immunoassay in 172 non-insulin-dependent diabetic patients with different grades of nephropathy and 64 non-diabetic control subjects, and were evaluated in comparison with those of urinary albumin, N-acetyl-beta-D-glucosaminidase (NAG) and alpha 1-microglobulin (alpha 1MG). These excretions were also compared between a group of non-diabetic renal disease (NDRD) patients (n = 24) and a subgroup of the diabetic patients studied (n = 76), whose urinary albumin excretion (UAE) varied within the ranges of micro- and macroalbuminuria. Of the diabetic patients studied, 49.7%, 53.4% and 32.4% had raised urinary albumin, NAG and alpha 1 MG excretion, respectively. In these patients, 54% and 53% exceeded the upper limit of normal for urinary IV-C and laminin. The level of IV-C and laminin excretion and the prevalence of their abnormal excretion showed a trend to increase with increasing grade of nephropathy, as assessed by UAE. In the normoalbuminuric [UAE < 20 mg/g creatinine (Cr)] stage, 28.3% and 26.3% patients had raised urinary IV-C and laminin excretion, respectively. In this stage, the excretion values for IV-C and laminin also rose significantly even when the UAE was < or = 10 mg/g Cr (P < 0.05 and P < 0.005, respectively). There was a close linear relationship between IV-C and laminin excretion (r = 0.73, P < 0.0001), together with their significant relationships with albumin, NAG and alpha 1MG excretion. The relationship of urinary IV-C and laminin with urinary NAG and alpha 1MG excretion remained significant even in normoalbuminuric patients. The normoalbuminuric patients with raised NAG and/or alpha 1MG excretion also had a higher prevalence of raised IV-C and laminin excretion than those with normal NAG and alpha 1MG excretion. The excretion values for IV-C and laminin, and the excretion ratios for IV-C/albumin and laminin/albumin were significantly higher in diabetic patients with evidence of incipient and clinical nephropathy than in NDRD patients, though the two patient groups had a comparable level of serum Cr and UAE. We conclude that the measurement of urinary IV-C and laminin may have potential for the evaluation of diabetic nephropathy. Furthermore, their determination might be helpful for distinguishing diabetic versus non-diabetic etiologies of altered renal function in diabetic patients.
Diabetes Res Clin Pract 1995 Jul
PMID:Urinary excretion of type IV collagen and laminin in the evaluation of nephropathy in NIDDM: comparison with urinary albumin and markers of tubular dysfunction and/or damage. 859 60


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