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

Acarbose is an alpha-glucosidase inhibitor proposed for the treatment of diabetic patients. It acts by competitively inhibiting the alpha-glucosidases in the intestinal brush border. The principal action of these enzymes is to convert nonabsorbable dietary starch and sucrose into absorbable monosaccharides (e.g. glucose). Enzyme inhibitors delay this conversion, slowing the formation and consequently the absorption of monosaccharides, and thus reducing the concentration of postprandial blood glucose. Both starch and sucrose are influenced, whereas lactose and glucose are not. Many studies in experimental animals, healthy volunteers and patients with non-insulin-dependent diabetes mellitus (NIDDM) have shown that acarbose decreases postprandial blood glucose, with a lesser reduction of fasting blood glucose, plasma triglycerides and postprandial insulin levels. In long term studies in NIDDM patients, acarbose significantly reduced glycosylated haemoglobin levels. Acarbose is only minimally absorbed from the gut and no systemic adverse effects have been demonstrated after long term administration. The drug allows undigested carbohydrates to pass into the large bowel where they are fermented causing flatulence, bloating and diarrhoea. These symptoms, which occur in approximately 30 to 60% of patients, tend to decrease with time and seem to be dose-dependent. They are minimised by starting therapy with low doses (such as 50mg 3 times daily) which may be effective in many patients. An increase in serum hepatic transaminases observed in earlier studies in the US, where doses of acarbose up to 900mg daily were used, has been not reported with the lower doses of the drug actually recommended [150 to 300mg (up to 600mg) daily]. In conclusion, acarbose may be useful in patients with NIDDM when diet alone is no longer able to maintain satisfactory blood glucose control. Furthermore, it may be a valid alternative to sulphonylurea or biguanide therapy when these drugs are contraindicated and insulin administration may be delayed. Acarbose seems also to be a useful adjunct to hypoglycaemic oral agents but its precise role in this field has not been fully clarified.
 ...
PMID:A risk-benefit appraisal of acarbose in the management of non-insulin-dependent diabetes mellitus. 772 53

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

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

Two rat models for non-insulin-dependent diabetes mellitus (NIDDM) have been used in our laboratory to study the effects of alpha-glucosidase inhibitors. These models become hyperglycaemic and have other characteristics which make them good models for NIDDM, and both prevention and reversal studies have been carried out; the prevention experiments were started before the animal became diabetic while the reversal groups were treated after diabetes had fully developed. In both models blood glucose was significantly lowered toward control levels using a dose of 40 mg per 100 g of diet while there was a less dramatic, but still significant, correction with half that dose. Treatment increased the weight gain of the more diabetic model (ZDF) while there was no effect of treatment on the weight of the Wistar diabetic fatty (WDF) rat. Other parameters such as glycated haemoglobins, nerve conduction velocity and nerve sugar content are also reversed with effective treatment of the hyperglycaemic condition.
 ...
PMID:alpha-Glucosidase inhibitors in diabetes: lessons from animal studies. 800 21

Orally taken alpha-glucosidase inhibitors are used for the management of diabetes mellitus. These drugs can prevent the postprandial rise of the blood glucose level by inhibiting the enzymatic digestion of carbohydrates in the intestinal lumen. Non-absorbable inhibitors such as acarbose are expected to function exclusively in the intestine, but absorbable inhibitors such as miglitol may exert an inhibitory effect on non-intestinal alpha-glucosidases present in the various cell types of the body. The potential side-effects of absorbable inhibitors are evaluated in this literature review. It is concluded that there is little risk of inducing unwanted side-effects when miglitol is taken in an oral dose of approximately 1 mg kg-1 body weight. The use of absorbable inhibitors is, however, not advised in case of kidney dysfunction.
 ...
PMID:An evaluation of the potential side-effects of alpha-glucosidase inhibitors used for the management of diabetes mellitus. 800 22

In Diabetes Mellitus, type IV collagen biosynthesis is increased: the alpha 1(IV) procollagen specific mRNA concentration is elevated, particularly in the kidney, and the type IV collagen protein is accumulating is the thickened basement membranes. Aldose reductase inhibitors like sorbinil do prevent basement membrane thickening and type IV collagen overproduction. The latter seems related to intracellular sorbitol accumulation and also to protein kinase C activation. Autocrine or paracrine TGF beta may be involved in the type IV collagen oversecretion. The secreted type IV collagen is subject to posttranslational alterations, especially glycation which leads to advanced glycation end-products and covalent crosslinks. This decreases collagen extractability and susceptibility to collagenases and favours basement membrane thickening. Disaccharide unit-specific alpha-glucosidase activity is inhibited by glucose (Kp = 7.5 mM). Type IV collagenase activity secreted by endothelial cells cultured at high glucose concentrations appears to be diminished. Therefore type IV collagen catabolism may be decreased in Diabetes Mellitus.
 ...
PMID:[Changes in collagen type IV metabolism in diabetes]. 801 6

Eight non-insulin-dependent diabetes mellitus patients, in whom oral hypoglycaemic agents were not effective, were treated with an alpha-glucosidase inhibitor, AO-128 (0.9 mg/day) for 6 months. After 6 months of treatment there was a statistically significant decrease in the blood glucose level 1 and 2 h postprandially. The 2 h blood glucose level was also significantly reduced after 2 months' treatment. The insulin and HbA1c levels after 2 and 6 months' treatment were lower than those before administration. Faecal weight, the frequency of bowel movements, the ratio of hydroxy fatty acids to total fatty acids, and faecal short-chain carboxylic acid content were all increased significantly during treatment. The initially hard stools became normal or soft, although no actual diarrhoea developed. Both faecal bile-acid excretion and the ratio of primary bile acids to total bile acids were increased significantly after 2 months, but they showed some recovery towards the pretreatment levels after 6 months' treatment. There was no distinct change in neutral sterol and fatty acid excretion. Breath hydrogen excretion showed a slight increase after treatment. These results suggest that intestinal fermentation was promoted and the intestinal transit time was shortened by AO-128 administration.
 ...
PMID:Effect of an alpha-glucosidase inhibitor on intestinal fermentation and faecal lipids in diabetic patients. 811 83

Diabetes is characterized by hyperphagia, polydipsia, polyuria, elevations in blood and urinary glucose, and alterations in the adrenergic nervous system. Insulin treatment is effective in reversing most of the adverse conditions of diabetes in the streptozotocin-treated rat. Acarbose (BAY G 5421), an intestinal alpha-glucosidase inhibitor, decreases postprandial glycemia by delaying carbohydrate absorption and also affords some beneficial effects in the diabetic animal. The purpose of this study was to evaluate the effects of chronic insulin (< or = 2 U/day) with and without acarbose treatment (20 mg/100 g of diet) on the metabolic and adrenergic parameters altered in streptozotocin (50 mg/kg, intravenously)-induced diabetes in female rats. Insulin dosage was changed weekly after the first 2 weeks of treatment in both insulin-treated groups in an attempt to maintain a level of blood glucose that was comparable to that achieved with acarbose treatment alone. Insulin dosage was reduced to a greater extent in the dual-treated group than in the group treated with insulin alone. Diabetic rats were hyperphagic, polydipsic, and polyuric within 1 week of streptozotocin treatment. Each treatment alone was effective in reducing these alterations. However, these reductions were more apparent in the combined therapy group. Only in this combined therapy group was glycated hemoglobin returned to normal. All treatments also prevented the significant weight loss observed in untreated diabetic animals. Adrenergic responses were assessed by monitoring the rise in tail skin temperature associated with administration of isoproterenol. Diabetic rats were less responsive than controls, and each of the treatments restored this response.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of insulin and acarbose alone and in combination in the female streptozotocin-induced diabetic rat. 830 97

The effect of the alpha-glucosidase inhibitor acarbose on retinal capillary basement membrane thickening was examined in the spontaneously diabetic BB/W-rat. Four months of diabetes resulted in significant thickening of the basement membranes of both the superficial and deep capillary nets of the retina. This characteristic change of the retinal microvasculature in diabetes was completely prevented by acarbose treatment that substantially reduced postprandial hyperglycemia. A similar but less pronounced effect was seen on the age-related increase in basement membrane thickening in acarbose-treated non-diabetic control rats who demonstrated decreased glycated hemoglobin levels compared to non-treated control rats. Significant positive correlations between basement membrane thickness and glycated hemoglobin area suggest that diabetic retinal microangiopathy may be prevented by lowering the cumulative glucose exposure to the microvasculature, and that age-related basement membrane thickening is mediated by long-term exposure to normal glucose levels.
Diabetes Res Clin Pract 1993 May
PMID:The effect of acarbose on diabetes- and age-related basement membrane thickening in retinal capillaries of the BB/W-rat. 837 64

The obese spontaneous hypertensive rat/NIH-corpulent (SHR/N-cp) rat exhibits some of the metabolic and pathologic alterations associated with non-insulin-dependent diabetes mellitus and hypertension. The current study was conducted to investigate the influence of phenotype (ob versus In) and source of dietary carbohydrate (sucrose versus starch) on intestinal sucrase, maltase, lactase, and alkaline phosphatase activity in SHR/N-cp rats. For 3 months, lean and obese male SHR/N-cp rats were fed isocaloric diets containing as the sole source of carbohydrate either 54% cooked corn starch or sucrose. Serum and urine markers for diabetes were observed in obese rats. Wet weight and length of intestines were significantly increased in obese rats compared with lean littermates. Among the intestinal enzymes measured, statistical tests confirmed that sucrase activity was significantly increased (P < 0.01) by both phenotype (ob > In) and feeding a sucrose diet. Diet alone (sucrose > starch) significantly increased (P < 0.05) maltase activity in obese rats, but had no effect on lean rats. Lactase activity was significantly higher (P < 0.05) in obese sucrose-fed rats compared with obese starch-fed and/or lean littermates. Statistical tests revealed that intestinal alkaline phosphatase activity was significantly altered (P < 0.05) by both phenotype and diet. Intestinal alkaline phosphatase was higher in starch-fed lean rats compared with lean littermates fed sucrose and to starch or sucrose-fed obese rats. These results are not indicative of a simple, nonspecific increase in intestinal enzyme activity, since the effects observed in intestinal alkaline phosphatase contrast the effects observed in intestinal sucrase, maltase, and lactase activity. These results indicate that both phenotype and diet alter structural and enzymatic intestinal activities of SHR/N-cp rats. Distinct variations in the observed intestinal enzymatic activities suggest that these enzymes are under the control of genetic, hormonal, and dietary factors. Rationale for these differences are discussed.
 ...
PMID:Effect of dietary carbohydrate and phenotype on sucrase, maltase, lactase, and alkaline phosphatase specific activity in SHR/N-cp rat. 843 90


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>