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)

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

Twenty patients with non-insulin-dependent diabetes mellitus who had been receiving appropriate dietary treatment for 3 months but whose glucose metabolism needed further improvement were treated with an alpha-glucosidase inhibitor. Treatment with the alpha-glucosidase inhibitor (0.6 mg/day) for 4 weeks, had no significant effect on blood glucose levels 2 h after breakfast or on glycosylated haemoglobin levels.
 ...
PMID:No effect of an alpha-glucosidase inhibitor on glucose metabolism in patients with non-insulin-dependent diabetes mellitus and low function of pancreatic beta cells. 758 73

1. We examined the effect of the alpha-glucosidase inhibitor acarbose on urinary albumin excretion (UAE) in streptozotocin diabetic rats. 2. Treatment with acarbose for 8 weeks after induction of diabetes prevented the significant increase in UAE observed in untreated diabetic rats relative to nondiabetic controls. 3. Acarbose significantly reduced integrated glycemia, which correlated with albumin excretion rates, and exerts a salutary effect on diabetic renal dysfunction.
 ...
PMID:Treatment with acarbose, an alpha-glucosidase inhibitor, reduces increased albumin excretion in streptozotocin-diabetic rats. 759 Jan 31

Acarbose (Glucobay-Bayer) is the first in a new class of oral antidiabetic drugs, the alpha-glucosidase inhibitors. It is licensed for the treatment of patients with non-insulin-dependent diabetes mellitus (NIDDM), either as first-line therapy when dietary measures are insufficient, or as an adjunct to conventional oral therapy where glycaemic control is suboptimal. The manufacturer claims that acarbose "can achieve a new level of blood glucose control in diabetes". In this article we consider whether acarbose offers any real advance.
 ...
PMID:Acarbose for non-insulin-dependent diabetes mellitus. 763 34

The only new pharmaceutical therapy for Type 2 (non-insulin-dependent) diabetes that has become available for clinical use in the last 40 years is the alpha-glucosidase inhibitor, acarbose, which reduces postprandial glucose levels by retarding digestion of complex carbohydrates in the gut. It has proved difficult to find other new metabolically active drugs that lack toxicity. Agents that reduce insulin resistance include the thiazolidinediones, which are very effective in animals. Of these, the only one that has been maintained in clinical evaluation appears from preliminary data to have an effect that although still useful, is not greater than that reported for current oral agents. Agents that reduce non-esterified fatty acid levels by inhibiting lipolysis, thereby allowing increased peripheral uptake of glucose, have so far given minimal reduction in glycaemia. The development of fatty acid oxidation inhibitors to reduce gluconeogenesis in the liver has been hampered by toxicity, but additional new agents are being studied. The most promising new approach for enhancing insulin secretion has been suggested by the demonstration that pharmacological doses of GLP-1 (7-36 amide), a natural enteric incretin hormone, improves pancreatic beta-cell and alpha-cell sensitivity to glucose and can induce normal basal glucose levels in diabetic man. The future development of GLP-1 agonists will be of great interest. This is timely as other insulin secretogogues, such as alpha 2 adrenergic blockers have proved relatively ineffective. Anti-obesity agents would in theory be beneficial, but have either had limited efficacy or have been avoided because of concern about long-term safety. Until new pharmaceutical agents become available, if near-normal glycaemia is to be achieved, many more Type 2 diabetic patients will need insulin therapy. When full insulin replacement therapy is not feasible, reducing the fasting blood glucose level towards normal with a single daily basal insulin supplement, either alone or in combination with oral agents, could become a more widely used therapy.
 ...
PMID:Drugs on the horizon for treatment of type 2 diabetes. 764 18

We investigated the relation between activities of islet glycogenolytic alpha-glucosidehydrolases and insulin secretion induced by glucose and 3-isobutyl-1-methylxanthine (IBMX) by means of suppressing 1) insulin release (Ca2+ deficiency) and 2) islet alpha-glucosidehydrolase activity (selective inhibition by the deoxynojirimycin derivative miglitol). Additionally, the in vivo insulin response to both secretagogues was examined. We observed that, similar to glucose-induced insulin release, islet glycogenolytic hydrolases (acid amyloglucosidase, acid alpha-glucosidase) were highly Ca2+ dependent. Acid phosphatase, N-acetyl-beta-D-glucosaminidase, or neutral alpha-glucosidase (endoplasmic reticulum) was not influenced by Ca2+ deficiency. In Ca2+ deficiency IBMX-induced insulin release was unaffected and was accompanied by reduced activities of islet alpha-glucosidehydrolases. Miglitol strongly inhibited glucose-induced insulin release concomitant with a marked suppression of islet alpha-glucosidehydrolase activities. Direct addition of miglitol to islet homogenates suppressed acid amyloglucosidase [half-maximal effective concentration (EC50) approximately 10(-6) M] and acid alpha-glucosidase. Acid phosphatase and N-acetyl-beta-D-glucosaminidase were unaffected. The miglitol-induced inhibition of glucose-stimulated insulin release was dose dependent (EC50 approximately 10(-6) M) and displayed a remarkable parallelism with the inhibition curve for acid amyloglucosidase. The in vivo insulin secretory response to glucose was markedly reduced in dystrophic mice (low amyloglucosidase), whereas the response to IBMX was unaffected. In summary, islet glycogenolytic hydrolases are Ca2+ dependent, and acid amyloglucosidase is directly involved in the multifactorial process of glucose-induced insulin release. In contrast the mechanisms of IBMX-stimulated insulin secretion operate independently of these enzymes. The effects of miglitol, a drug currently used in diabetes therapy, deserves further investigation.
 ...
PMID:Ca2+ deficiency, selective alpha-glucosidehydrolase inhibition, and insulin secretion. 768 25

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


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