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

---

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

Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.
...
PMID:Effect of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor, on glucose, insulin, C-peptide and GIP responses to an oral sucrose load in patients with post-prandial hypoglycaemic symptoms. 188 80

Rat pancreatic endocrine tumours were induced by administration of streptozotocin plus nicotinamide. Fifteen to eighteen months later tumours with wet weights of 0.1 to 224 mg were isolated. These tumours were compared with normal rat pancreatic islets. Insulin release from perifused tumours was stimulated by D-glucose, L-leucine, 2-ketoisocaproate, and D-glyceraldehyde, potentiated by theophylline and inhibited by norepinephrine. Compared with isolated rat pancreatic islets, however, insulin secretory responsiveness to glucose stimulation and insulin content were reduced in tumour tissue. Hypoglycaemia in tumour bearing rats and impaired diffusion of insulin out of the tumours may explain this difference. The pattern of enzyme activities observed in tumour tissue was typical for pancreatic endocrine tissue. The activities of succinate dehydrogenase, the two types of the monoamine oxidase, and alpha-glucosidase were in the normal range in tumour tissue. Only the activities of 5'nucleotidase and glutamate dehydrogenase were decreased. Immunocytochemical analysis of the tumours revealed that they contained an average of 91% B-cells. In addition 8% of D-cells were encountered. Proportions of A-cells and PP-cells ranged below 1%. Thus this endocrine tumour of the pancreas with a high proportion of functionally intact B-cells is an interesting model for studying regulation of secretion and endocrine tumour development.
...
PMID:Secretory, enzymatic, and morphological characterization of rat pancreatic endocrine tumours induced by streptozotocin and nicotinamide. 299 5

Bay-m-1099, a new alpha-glucosidase inhibitor, was given along with insulin immediately before standard breakfasts, lunches and dinners to nine insulin-dependent diabetic patients to determine whether this combination therapy would produce postprandial glycemic control comparable to that achieved when insulin alone was administered 30 min prior to eating. To avoid potential hypoglycemia, 20% less insulin (0.12 vs. 0.15 U/kg) was given with Bay-m-1099. Despite plasma free insulin concentrations which were less than those observed when insulin alone was given (9.4 +/- 1.0 vs. 12.8 +/- 1.6 microU/ml/min, area under curves for all meals), postprandial hyperglycemia (area under curve) was not significantly different (P greater than 0.1) when insulin plus Bay-m-1099 was administered immediately before each meal (124 +/- 26 mg/ml/min) than when insulin was administered 30 min before each meal (113 +/- 17 mg/ml/min). Thus, the combination of immediate preprandial administration of an alpha-glucosidase inhibitor along with insulin resulted in glycemic control comparable to that achieved when more insulin was taken 30 min prior to eating. We conclude that use of alpha-glucosidase inhibitors could lessen the inconvenience of intensive insulin regimens by permitting patients to take their insulin immediately before eating and thus result in greater patient compliance.
...
PMID:Alpha-glucosidase inhibition and timing of preprandial insulin in patients with insulin-dependent diabetes mellitus (IDDM). 328 68

Acarbose delays the production of monosaccharides (notably glucose) by inhibiting the alpha-glucosidases associated with the brush-border membrane of the small intestine which are responsible for the digestion of complex polysaccharides and sucrose. In healthy subjects acarbose 100 to 200 mg significantly inhibits postprandial glucose, insulin and triglyceride responses, with some evidence of carbohydrate malabsorption with the higher dose. Clinical trials in patients with non-insulin-dependent diabetes mellitus showed that acarbose improved diabetic control, especially postprandial blood glucose levels, independent of whether the patients were receiving concomitant oral antidiabetic drugs in addition to dietary management. In comparative studies acarbose was significantly superior to placebo, and comparable to biguanides, when used alone or as an adjuvant to sulphonylurea therapy. Trials in patients requiring insulin to control their diabetes demonstrated that acarbose significantly reduced postprandial blood glucose concentrations, resulting in a smoother diurnal blood glucose-time curve and improved symptoms associated with nocturnal hypoglycaemia. Daily insulin requirements were sometimes reduced. In large multicentre trials acarbose up to 600 mg/day for 3 to 12 months improved glycaemic control in approximately 55% of patients with non-insulin-dependent or insulin-dependent diabetes mellitus. Apart from its use in diabetes, encouraging preliminary results have been obtained with acarbose in other therapeutic areas such as dumping syndrome, reactive hypoglycaemia, and types IIb and IV hyperlipoproteinaemias--however, further clinical experience is needed in these settings before clear conclusions can be drawn. No serious side effects have been reported during treatment with acarbose, although it is associated with a high incidence of troublesome gastrointestinal symptoms such as flatulence, abdominal distension, borborygmus and diarrhoea. The incidence of these reactions usually decreases with time. Thus, acarbose represents the first of a new class of oral antidiabetic drugs--the alpha-glucosidase inhibitors. It has proven useful for improving glycaemic control when used as an adjunct to standard therapy involving dietary restriction, oral antidiabetic drugs and/or subcutaneous insulin. That being the case, acarbose should provide the clinician with an interesting treatment option which can be used in a broad range of patients with diabetes mellitus in whom 'traditional' management approaches produce suboptimal glycaemic control.
...
PMID:Acarbose. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential. 328 12

Nocturnal hypoglycemia is common in the diabetic patient on twice-daily regular and intermediate (NPH or lente) insulin regimens because intermediate-acting insulins before the main evening meal produce "unopposed" free insulin peaks around 0300 h, food absorption having been completed much earlier. Fourteen insulin-dependent diabetic patients were treated for 6 wk with the alpha-glucosidase inhibitor, acarbose, in a double-blind crossover study to see whether the drug would delay absorption of the evening meal sufficiently to correct the mismatch and prevent nocturnal hypoglycemia. On 200 mg acarbose (six patients), inhibition of carbohydrate digestion was so profound as to lead to midevening hypoglycemia with severe flatulence and abdominal colic. With a smaller dose of 100 mg before the evening meal (eight patients) there was a significant reduction in MAGE and MBG coupled with a clinically significant reduction in midevening and nocturnal hypoglycemic reactions. Alpha-glucosidase inhibition therefore provides a promising new approach to the problem of nocturnal hypoglycemia although a preparation that is safe for long-term clinical use remains to be found.
...
PMID:A new approach to the treatment of nocturnal hypoglycemia using alpha-glucosidase inhibition. 640 Jul 9

Ten patients with non-insulin-dependent diabetes mellitus who were being treated with a sulphonylureal compound but whose glucose metabolism needed further improvement were given a combination of their usual sulphonylurea treatment and an alpha-glucosidase inhibitor. Treatment with the alpha-glucosidase inhibitor (0.6 mg/day), in addition to glibenclamide (7.5 mg/day in two patients; 5.0 mg/day in four; 2.5 mg/day in one) or tolbutamide (500 mg/day in three patients) for 4 weeks, improved hyperglycaemia after meals from 237-247 mg/dl to 192 mg/dl, and reduced glycosylated haemoglobin levels from 8.5-8.6% to 7.9% without causing hypoglycaemia.
...
PMID:Effect of an alpha-glucosidase inhibitor combined with sulphonylurea treatment on glucose metabolism in patients with non-insulin-dependent diabetes mellitus. 758 71

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) affects middle-aged or elderly people who frequently have several other concomitant diseases, especially obesity, hypertension, dyslipidaemias, coronary insufficiency, heart failure and arthropathies. Thus, polymedication is the rule in this population, and the risk of drug interactions is important, particularly in elderly patients. The present review is restricted to the interactions of other drugs with antihyperglycaemic compounds, and will not consider the mirror image, i.e. the interactions of antihyperglycaemic agents with other drugs. Oral antihyperglycaemic agents include sulphonylureas, biguanides--essentially metformin since the withdrawn of phenformin and buformin--and alpha-glucosidase inhibitors, acarbose being the only representative on the market. These drugs can be used alone or in combination to obtain better metabolic control, sometimes with insulin. Drug interactions with antihyperglycaemic agents can be divided into pharmacokinetic and pharmacodynamic interactions. Most pharmacokinetic studies concern sulphonylureas, whose action may be enhanced by numerous other drugs, thus increasing the risk of hypoglycaemia. Such an effect may result essentially from protein binding displacement, inhibition of hepatic metabolism and reduction of renal clearance. Reduction of the hypoglycaemic activity of sulphonylureas due to pharmacokinetic interactions with other drugs appears to be much less frequent. Drug interactions leading to an increase in plasma metformin concentrations, mainly by reducing the renal excretion or the hepatic metabolism of the biguanide, should be avoided to limit the risk of hyperlactaemia. Owing to its mode of action, pharmacokinetic interferences with acarbose are limited to the gastrointestinal tract, but have not been extensively studied yet. Pharmacodynamic interactions are quite numerous and may result in a potentiation of the hypoglycaemic action or, conversely, in a deterioration of blood glucose control. Such interactions may be observed whatever the type of antidiabetic treatment. They result from the intrinsic properties of the coprescribed drug on insulin secretion and action, or on a key step of carbohydrate metabolism. Finally, a combination of 2 to 3 antihyperglycaemic agents is common for treating patients with NIDDM to benefit from the synergistic effect of compounds acting on different sites of carbohydrate metabolism. Possible pharmacokinetic interactions between alpha-glucosidase inhibitors and classical antidiabetic oral agents should be better studied in the diabetic population.
...
PMID:Antihyperglycaemic agents. Drug interactions of clinical importance. 774 82

With alpha-glucosidase inhibitors generally improved metabolic control is achieved in NIDDM patients regardless of whether acarbose is administered in addition to other oral anti-diabetic agents or to diet alone. The most significant finding is the reduction of postprandial blood glucose concentrations. Long-term studies show a decrease in glycosylated haemoglobin and often also in fasting blood glucose levels. Placebo-controlled studies have proven that postprandial insulin concentrations are decreased under acarbose treatment while fasting plasma insulin is usually unchanged. The major side-effects of acarbose treatment involve the gastrointestinal system and include flatulence, abdominal discomfort and diarrhoea. Symptoms diminish with treatment time and are less severe when the treatment is started with low doses. Acarbose should usually be initiated as a 50 mg dose immediately before each major carbohydrate containing meal. Monotherapy with acarbose does not cause hypoglycaemia, however, hypoglycaemia may occur with combination of sulphonylurea or insulin treatment by the well-known reasons. In this case hypoglycaemia has to be treated by taking glucose.
...
PMID:alpha-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. 800 25

For 10 patients (three women and seven men) with noninsulin-dependent diabetes mellitus, who had been given insulin (22.6 +/- 19.6 U/day) and had frequently shown hypoglycaemia, the insulin dose was slightly reduced and the administration of an alpha-glucosidase inhibitor was simultaneously started. Hypoglycaemic symptoms disappeared immediately and completely, and sugar metabolism immediately before the withdrawal of treatment was not aggravated: the glycosylated haemoglobin level was unchanged and the post-prandial blood glucose level was increased though not significantly. The results of the present study indicate that the combined used of an alpha-glucosidase inhibitor with a reduced insulin dose improves the quality of life of patients and may improve hyperinsulinaemia.
...
PMID:Can alpha-glucosidase inhibitors reduce the insulin dosage administered to patients with non-insulin-dependent diabetes mellitus? 874 17

The effects of treatment with an alpha-glucosidase inhibitor and a reduced dose of sulphonylurea were investigated in patients with non-insulin-dependent diabetes mellitus who had previously been treated with sulphonylurea compounds but who were hypoglycaemic at times. Treatment with a daily dose of 0.6 mg alpha-glucosidase inhibitor and a reduced dose of the previously used sulphonylurea compound for 4 weeks did not significantly affect the glycosylated haemoglobin level. The post-prandial blood-glucose concentration of the patients was unchanged after treatment compared with its value immediately before treatment but differed significantly compared with the value 4 weeks before treatment (P < 0.03); it was considered likely that this change was due to a seasonal increase in calorie intake at the end of the treatment period. Symptoms related to hypoglycaemia disappeared in all of the treated patients.
...
PMID:Can alpha-glucosidase inhibitors reduce the dosage of sulphonylurea compounds needed by patients with non-insulin-dependent diabetes mellitus? 874 20


1 2 3 4 5 6 7 8 9 Next >>

---