Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.20 (alpha-glucosidase)
4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The urinary excretion of lactate dehydrogenase, gamma-glutamyltransferase, alkaline phosphatase, arylsulphatase A, alpha-glucosidase, beta-galactosidase, trehalase, N-acetyl-beta-glucosaminidase, beta-glucuronidase, and leucine arylamidase was studied in 68 patients with biopsy-proved glomerular, 54 with interstitial renal disease and in 97 patients suffering from primary hypertension. The enzyme output of these 219 patients was compared to that of a reference population of 100 thoroughly selected healthy subjects. The highest incidence of elevated enzyme excretion was observed for N-acetyl-beta-glucosaminidase with 88% in glomerulopathies and 78% in interstitial disease, followed by beta-galactosidase. 94% of the patients with glomerular kidney disease, 90% of those with interstitial disease and about 60% of the subjects with primary benign hypertension revealed an output of at least one enzyme above upper reference limit. The highest average enzymuria occured in glomerulopathies, particularly high values in patients with the nephrotic syndrome. Application of discriminant analysis to the urinary enzyme pattern of glomerular and interstitial renal diseases resulted in an overall correct classification into the appropriate group of 89% of all patients. The discrimination between glomerular and interstitial disease was better in patients with normal renal function than in those with reduced function. Results show, that the analysis of urinary enzyme patterns may be a helpful adjunct for differential diagnosis of kidney diseases.
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PMID:Evaluation of urinary enzyme patterns in patients with kidney diseases and primary benign hypertension. 3 57

AO-128 is a potent and structurally novel inhibitor of the intestinal disaccharidases, such as maltase and sucrase. Genetically obese-diabetic mice, KKA(y), were used to examine the acute or long-term effectiveness of this compound. AO-128 decreased a postprandial rise in blood glucose after sucrose solution loading dose-dependently; the ED50 to reduce a delta increment of blood glucose by 50% was 0.22 mg/kg. The intestinal sucrase and maltase activities were suppressed to 7 and 48% of the control levels, respectively, at a dose of 0.21 mg/kg. Four-week-old female KKA(y) mice were kept on a laboratory diet containing 10 or 50 ppm of AO-128 for 12 weeks. The high dose of AO-128 reduced food intake and body weight gain throughout the experimental period. On the other hand, the low dose reduced body weight gain for the first 4 weeks without any effect on food intake. Development of the hyperglycemia and hyperinsulinemia characteristic of KKA(y) mice was moderately prevented by the low dose, and completely by the high dose. Hypertriglyceridemia tended to be suppressed by the AO-128 treatment. The high dose decreased the hemoglobin A1 level and parametrial adipose tissue weight. Hepatomegaly and fatty liver were ameliorated by AO-128 dose-dependently. Nephropathy was ameliorated by the high dose. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
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PMID:Antiobesity and antidiabetic actions of a new potent disaccharidase inhibitor in genetically obese-diabetic mice, KKA(y). 162 84

Few data are yet available comparing the histological patterns of cadmium nephropathy with the values of urinary enzyme excretions, useful indexes of renal tubular damage. 40 Wistar rats, divided into four groups (A-D), were intoxicated with cadmium chloride (CdCl2) at 16 ppm in drinking water for 4, 16, 40 and 60 weeks, respectively. At the end of each period all the intoxicated rats and 5 controls were assessed for creatinine clearance, fractional excretion of gamma-glutamyltransferase (UfrGGT) and alpha-glucosidase (UfrAGL), indexes of anatomical tubular damage, and for fractional clearance of lysozyme (CfrLys), index of functional tubular damage. Thereafter, the rats were sacrificed and their kidneys examined with light and electron microscopy. Control rats and group A and B rats did not show any histological impairment. A widespread vesiculation of proximal tubular cells with mitochondrial and lysosomal alterations was found in the group C rats and was more evident in group D. The brush border never showed any damage in all groups in accordance with the finding of a normal excretion pattern of UfrGGT, an enzyme situated in this structure. The UfrAGL was increased only in group D rats (p less than 0.025), who showed the most severe anatomical damages. The CfrLys, an index of tubular function, was elevated in group C and D rats (p less than 0.02 and p less than 0.002, respectively). It was possible to detect the initial renal tubular damage.
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PMID:Detection of the early steps of cadmium nephropathy--comparison of light- and electron-microscopical patterns with the urinary enzymes excretion. An experimental study. 256 73

The recovery of tubules after relief of obstructive nephropathy may be investigated through serial assessment of the urinary excretion of tubular enzymes alpha-glucosidase, gamma-glutamyl-transferase and N-acetyl glucosaminidase as well as of the microprotein beta-2-microglobulin. We studied 21 patients in whom obstructive nephropathy was relieved by operative or nonoperative methods. Anuria persisted from 2 to 14 days. In these patients urinary excretion of alpha-glucosidase, gamma-glutamyl-transferase, N-acetyl glucosaminidase and beta-2-microglobulin, as well as the serum creatinine were assessed weekly. Serum creatinine was the earliest index to return to normal (within 9 to 26 days). Enzymuria returned to normal within 35 to 45 days, whereas normal urinary excretion of beta-2-microglobulin occurred more than 100 days after relief of obstructive nephropathy. N-acetyl glucosaminidase and gamma-glutamyl-transferase proved to be more reliable than alpha-glucosidase in detecting recovery of the luminal membrane of the proximal tubule. The return to normal of urinary beta-2-microglobulin levels has been shown to occur later, since more specific and complex intracellular functions underlie this index. The pathophysiological aspects of recovery of obstructive nephropathy may be considered similar to those observed in ischemic acute renal failure, since in both instances hemodynamic changes are involved.
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PMID:Tubule recovery after obstructive nephropathy relief: the value of enzymuria and microproteinuria. 288 28

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem which occurs predominantly in the older population; 16.8% of persons over age 65 years have NIDDM. The total health costs of NIDDM are in excess of $US20 billion annually. The primary objective in the treatment of NIDDM is to achieve normoglycaemia, without aggravating coexisting abnormalities. Common abnormalities include obesity, hypertension, retinopathy, nephropathy and neuropathies. Diet, and consequent bodyweight reduction, is the cornerstone of therapy for NIDDM. Total calorie intake should be limited, while the percentage of calories from carbohydrates should be increased and that from fats and cholesterol should be decreased. Exercise may also help to reduce bodyweight. Sulphonylurea drugs stimulate insulin secretion from beta-cells, and may be a useful adjunct to nonpharmacological therapy. Failure to respond to sulphonylurea drugs may be primary (25 to 30% of initially treated patients) or secondary (5 to 10% per year). It is not clear which is the most effective pharmacological intervention in such cases. Options include switching to or combining therapy with insulin, a biguanide, or other insulin-sparing antihyperglycaemic agents, e.g. alpha-glucosidase inhibitors, thiazolidinediones, chloroquine or hydroxychloroquine, or fibric acid derivatives such as clofibrate. Other experimental agents include the fatty acid oxidation inhibitors and dichloroacetate. Specific agents, such as antihypertensives, lipid lowering agents and sorbitol inhibitors, may be needed to prevent the complications arising from the spectrum of clinical and metabolic abnormalities which arise from insulin resistance.
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PMID:Treatment of non-insulin-dependent diabetes mellitus and its complications. A state of the art review. 807 74

It is expected that the number of patients with diabetes mellitus will increase in the near future. The high rate of microvascular and macrovascular complications developing in these patients will place an even higher burden on our healthcare systems. Several pathophysiological factors are involved in the development of complications, among which are hyperglycaemia per se, the consequent formation of advanced glycation end-products (AGEs) and the intracellular accumulation of sorbitol. In addition, hypertension and dyslipidaemia also play an important role, especially in the development of coronary heart disease and stroke. The major therapeutic goals in patients with non-insulin-dependent diabetes mellitus (NIDDM) are to reduce obesity and normalise lipid disturbances and increased blood pressure, in order to improve the well-being of the patient and reduce the risk of the development of late diabetic complications. Often, pharmacological treatment of the hyperglycaemia is necessary, in which case sulphonylureas, metformin, alpha-glucosidase inhibitors such as acarbose, or insulin may be employed. It is believed that medical interventions, by their effect on improving metabolic control, reduce the incidence and severity of diabetic complications, especially when considering the toxic effects of glucose and the accumulation of AGEs as a consequence of raised tissue glucose levels. This concept is also based on extrapolation of the finding of the Diabetes Control and Complications Trial that intensive glycaemic control in IDDM will prevent the progression of at least the microvascular complications like retinopathy and nephropathy. There are, however, no long term studies in NIDDM patients to show that treatment with oral antihyperglycaemic agents helps to postpone or prevent complications. It is expected that the UK Prospective Diabetes Study will show whether better metabolic control, either with oral antihyperglycaemics or with insulin, will indeed improve outcome. Several other studies aiming at specific risk factor intervention (hypertension, hyperlipidaemia, lipid oxidation) in NIDDM patients are currently ongoing.
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PMID:Prevention of complications in non-insulin-dependent diabetes mellitus (NIDDM). 852 59

The development of the alpha-glucosidase inhibitor acarbose provides a new approach in the management of diabetes. By competitive and reversible inhibition of intestinal alpha-glucosidases, acarbose delays carbohydrate digestion, prolongs the overall carbohydrate digestion time, and thus reduces the rate of glucose absorption. After oral administration of acarbose, the postprandial rise in blood glucose is dose-dependently decreased, and glucose-induced insulin secretion is attenuated. Because of diminished postprandial hyperglycemia and hyper-insulinemia by acarbose, the triglyceride uptake into adipose tissue, hepatic lipogenesis, and triglyceride content are reduced. Therefore, acarbose treatment not only flattens postprandial glycemia, due to the primary and secondary pharmacodynamic effects, but also ameliorates the metabolic state in general. In diabetic animals, acarbose reduced urinary glucose loss, the blood glucose area under the curve, and prevented the decrease in skeletal muscle GLUT4 glucose transporters. As a consequence of the reduced mean blood glucose area under the curve, the amount of protein nonenzymatically glycated was diminished, as was the formation of advanced glycation end-products (AGEs). The prevention of basement membrane glycation and thickening in various tissues indicated that acarbose treatment of diabetic animals produced beneficial effects against the development of nephropathy, neuropathy, and retinopathy. Thus, the alpha-glucosidase inhibitor acarbose may have the potential to delay or possibly prevent the development of diabetic complications.
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PMID:The mechanism of alpha-glucosidase inhibition in the management of diabetes. 854 17

Non-insulin-dependent diabetes mellitus (NIDDM) is a major health concern for clinicians who are responsible for the care of an aging population. The relationship between hyperglycemia and the chronic complications of retinopathy, nephropathy, and neuropathy has been established in patients with insulin-dependent diabetes mellitus, and it is extremely likely that such a relationship exists in patients with NIDDM as well. Diet and exercise are the cornerstone for the management of NIDDM. The assessment of glycemic control should determine which patients with NIDDM need more aggressive intervention to control hyperglycemia. Pharmacologic treatment options include oral administration of the sulfonylureas, a biguanide, and an alpha-glucosidase inhibitor and subcutaneous administration of insulin. Extensive education about diabetes and self-monitoring of blood glucose levels are important components in maximizing glycemic control. Additional pharmacologic treatment options are necessary when adequate individualized treatment goals are not attained. The goal of therapy is to prevent the onset or progression of long-term microvascular and macrovascular complications. In this review, we present the therapeutic options and outline our approach to the pharmacologic treatment of NIDDM. Relevant medical literature on each treatment modality is reviewed, and the cost of therapy with use of each medication is provided.
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PMID:Pharmacologic treatment options for non-insulin-dependent diabetes mellitus. 900 95

In patients suffering from insulin-dependent diabetes mellitus (IDDM) with or without preclinical and clinical signs of diabetic nephropathy, the degree of epithelial cell lesions in the renal tubules was assessed from the urinary activities of enzymes at various sites, such as lysosomal (N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (beta-GA)), brush edge membranous (alanine aminopeptidase (AAP), and cytosolic (alpha-glucosidase (alpha-GL)). Patients from Groups 1 and 2 had no preclinical and clinical signs of nephropathy. In Group 1 patients, the magnitude of enzymuria was not different from that in normalcy. However, Group 2 patients exhibited significant increases in urinary NAG and beta-GA activities as compared to Group 1 patients and healthy individuals. In Group 3 patients with microproteinuria from 0.05 to 0.5 mg protein per ml urine, displayed a further enhancement of NAG and beta-GA activities as compared to Group 2 patients and significantly higher activity than did Groups 1 and 2 patients and healthy individuals. In Group 4 patients with macroproteinuria of > 0.5 mg/ml), greater increases in the activities of NAG, beta-GA, and AAP were not found, however, there was a significant increase in alpha-G1 activity. The findings suggest the varying degrees of epithelial cell damage in the renal tubules in patients of different groups and the possibility of early detection of lesion in the proximal portion of nephronic tubules in IDDM patients as assessed from urinary enzyme levels.
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PMID:[Urinary enzymes in insulin-dependent diabetes mellitus]. 899 62

The use of insulin in elderly patients raises special considerations. Most people who develop diabetes mellitus late in life have type 2 diabetes mellitus, in which there is some residual endogenous insulin secretion. This pancreatic insulin secretion, when present, stabilises their metabolic status. However, some elderly people lose virtually all their endogenous insulin secretory capacity over time, or may even have type 1 (autoimmune) diabetes mellitus with no endogenous insulin. Generally, older patients with diabetes mellitus can be managed for years, often decades, with nutritional therapy and oral agents. More options exist now than did previously. In addition to a variety of sulfonylureas, there is metformin, troglitazone, and/or alpha-glucosidase inhibitors, that are viable options to be used before turning to insulin. The goals of insulin therapy in the elderly must be considered. When hyperglycaemia causes symptoms (polyuria, polydypsia and bodyweight loss) blood glucose levels are generally >200 mg/dl, and insulin is needed if maximal doses of oral agents have been used. Insulin is also indicated when hyperglycaemia puts patients at risk of hyperosmolar states, for example, when blood glucose is >300 mg/dl during a normal day. Clinical judgement dictates whether to use insulin to control glycaemia in the attempt to avoid long term complications such as neuropathy, retinopathy or nephropathy. In people with relatively short life expectancy, major comorbities and no sign of diabetic complications, the risk may be small. On the other hand, in patients for whom neuropathy, in particular, is a major risk, controlling glycaemia (with insulin if necessary) does reduce that risk. Most patients with type 2 diabetes mellitus can be managed with relatively simple insulin regimens thanks to their endogenous insulin secretion. A single bedtime dose of neutral protamine Hagedorn (NPH) insulin, with or without continuation of daytime oral agents, may control fasting blood glucose. A pre-mix combination of NPH and Regular insulin such as 70/30 or 50/50 may be used pre-meal. More customised, 'intensive' insulin regimens are needed when the glycaemia is unstable. Hypoglycaemia is clearly the most significant risk of insulin therapy. If mild and easily treated, it is of no real concern. On the other hand, nocturnal hypoglycaemia, and, in particular, hypoglycaemia unawareness, are clear signs that the insulin regimen should be modified. In summary, insulin therapy may be necessary, and can be used effectively, in elderly patients. However, risk:benefit considerations must be taken into account when deciding which patients to treat with insulin and what insulin regimen to use.
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PMID:Feasibility and outcomes of insulin therapy in elderly patients with diabetes mellitus. 1040 37


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