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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of combined insulin-glibenclamide therapy on glucose control was evaluated in a double-blind placebo controlled study of 20 patients with non-insulin-dependent diabetes mellitus (NIDDM) and second failure to oral antidiabetic therapy with glibenclamide or glipizide. After an observation period of 1-3 months, insulin treatment was initiated which resulted in rapid improvement of the glycemic control within 6 weeks. Thereafter glibenclamide or placebo was added to insulin for a further 12 weeks. Glibenclamide improved the glycemic control as expressed by a diminution of blood glucose and HbA1c. This was observed in spite of the fact that the daily insulin dose was reduced by approximately 30% in the glibenclamide-treated group of patients. It is concluded that in NIDDM patients with second failure to glibenclamide ot glipizide therapy, the responsiveness to glibenclamide may be at least partially restored by a short period of insulin treatment. It is suggested that therapy with insulin and glibenclamide is an appropriate treatment regimen for NIDDM patients with second failure to sulfonylurea therapy.
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PMID:Glibenclamide improves the response to insulin treatment in non-insulin-dependent diabetics with second failure to sulfonylurea therapy. 312 26

Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.
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PMID:Adverse cardiovascular effects of sulphonylurea drugs. Clinical significance. 329 23

The effects of long-term exposure of cultured rat adipose tissue to glyburide were examined on glycogen synthase activity. Glyburide alone caused an increase in the activity ratio (low glucose-6-P/high glucose-6-P) of glycogen synthase, and enhanced insulin's activation of the enzyme. The glyburide effects were time dependent, requiring fat pieces to be exposed to the drug for at least 10-20 h. The glucose concentration in the culture medium was also important: optimal concentrations of glucose were 10-20 mM. Glyburide acted to shift the insulin dose-response curve to the left by a factor of 2.5, but did not enhance the effects of maximal concentrations of the hormone. The Ka of the glyburide effects was about 2.0 microM. If glucose was omitted during the 20-min incubation with or without insulin, the increase in the activity ratio of glycogen synthase by glyburide was unaffected, but the enhancement of insulin action was reduced. Because these data indicate that glyburide's actions are glucose dependent, we propose that the sulfonylurea is probably acting to increase glucose transport, thus allosterically increasing the activity of a synthase phosphatase by glucose-6-P. The net result of this would be increased dephosphorylation and activation of glycogen synthase.
Diabetes 1985 Mar
PMID:Insulin-like and insulin-enhancing effects of the sulfonylurea glyburide on rat adipose glycogen synthase. 391 1

Glyburide, a second-generation hypoglycemic sulfonylurea, is 200 times as potent as tolbutamide. This increase is due to greater intrinsic hypoglycemic potency of the molecule rather than to a prolonged biologic half-life. Glyburide is inactivated by the liver to 4-trans-hydroxyglyburide and 3-cis-hydroxyglyburide; 50% of these compounds is excreted in the urine and 50% in the bile. Although the serum concentration of glyburide can be measured by radioimmunoassay and high-performance liquid chromatography, the importance of its serum concentration in the reduction of hyperglycemia is not yet established. Glyburide has a therapeutic effectiveness comparable to that of the first-generation sulfonylurea chlorpropamide; however, it has a lower frequency of adverse effects. To date it has a low frequency of clinically significant interactions with other drugs. Glyburide should not be prescribed for patients with liver disease or significant renal disease. Because glyburide is a potent hypoglycemic agent, it should be prescribed in small initial doses, particularly for elderly patients with diabetes. At the present time there is no definite evidence that it modifies the increased risk of cardiovascular disease of diabetic patients. Although glyburide is a potent stimulator of pancreatic insulin secretion after short-term administration, an additional mechanism of action during long-term administration is to decrease the resistance of muscle and liver to the action of insulin. It is a useful medication for patients with type II diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first-generation sulfonylureas.
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PMID:Glyburide: a second-generation sulfonylurea hypoglycemic agent. History, chemistry, metabolism, pharmacokinetics, clinical use and adverse effects. 392 53

Glyburide, a second-generation sulfonylurea compound, was combined with insulin to evaluate its therapeutic effectiveness in 14 patients with non-insulin-dependent diabetes mellitus (NIDDM), poorly controlled by insulin alone. Patients were studied before and three months after the addition of glyburide to their insulin program. Fasting plasma glucose concentration fell an average of 57 mg/dL, associated with an approximately 25% reduction in postprandial glucose response. Therapeutic responses varied widely from patient to patient; the greatest improvement in diabetic control was seen in heavier patients, who had retained the ability to secrete insulin in response to meals and who were not excessively insulin resistant. The glyburide-induced fall in plasma glucose concentration was associated with improvements in both insulin secretion and insulin action, but only the enhanced insulin action correlated with the reduction in fasting and postprandial glucose levels. Thus, diabetic control was significantly improved by glyburide. Combined insulin-sulfonylurea therapy may be useful in the treatment of NIDDM that cannot be easily controlled with either agent alone.
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PMID:Glyburide in non-insulin-dependent diabetes. Its therapeutic effect in patients with disease poorly controlled by insulin alone. 392 61

Despite more than a quarter of a century of use in managing type II diabetes, the mechanism responsible for the hypoglycemic action of sulfonylurea agents remains controversial. To identify factors responsible for the clinical response to the drug, glycemic control, endogenous insulin secretion in response to mixed meals, adipocyte insulin binding, insulin-mediated peripheral glucose disposal as well as basal hepatic glucose output were assessed in 17 type II diabetic subjects before and after three months of therapy with glyburide, a second-generation sulfonylurea. To determine if the response to the drug changed with time, nine of the subjects were treated for an additional 15 months. Glyburide therapy increased endogenous insulin secretion, increased adipocyte insulin binding after 18 but not three months of therapy, enhanced peripheral insulin action by acting primarily at a post-receptor site, and reduced basal hepatic glucose output. The increase in post-receptor function and the reduction of basal hepatic glucose output appear to be the crucial determinants of the clinical response to the sulfonylurea; the response pattern to sulfonylurea compounds can vary as a function of the duration of treatment. An accelerated rate of basal hepatic glucose output appears to be the major cause of secondary failure in glyburide-treated patients.
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PMID:Longitudinal evaluation of the effects of sulfonylurea therapy in subjects with type II diabetes mellitus. 393 59

Glyburide and other sulfonylureas consistently enhance receptor binding in cells from patients with non-insulin-dependent diabetes mellitus, whereas no effects and mixed effects have been demonstrated in cells from patients with insulin-dependent diabetes mellitus and in normal cells, respectively. These findings indicate that the experimental model may be critical in demonstrating sulfonylurea effects on receptor binding. Postbinding function studies have shown a definite enhancement of peripheral glucose metabolism by sulfonylurea drugs; such post-receptor changes have not clearly correlated with receptor binding alterations. Studies using mouse-cultured myocytes indicate that both glyburide and tolazamide have stimulatory effects on glucose uptake, whereas only glyburide caused an increase in receptor binding. The data suggest a major and widespread post-receptor function for the sulfonylurea drugs, particularly glyburide, possibly mediated through pathways similar but not identical to insulin pathways. The direct receptor effects, in contrast, are possibly more tissue-specific and/or disease-dependent. In non-insulin-dependent diabetes mellitus, these drugs exert clinical efficacy by acting through both mechanisms.
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PMID:Dual actions of sulfonylureas and glyburide. Receptor and post-receptor effects. 393 60

Twenty-seven patients with non-insulin-dependent diabetes mellitus and fasting plasma glucose values greater than 140 mg/dl began glyburide therapy. After entry into the study, patients were classified into three phenotypes on the basis of their initial lipoprotein profile: type IV, mixed, and normal. Glyburide lowered plasma glucose and raised plasma insulin concentrations in non-insulin-dependent diabetes mellitus. Patients with type IV hyperlipoproteinemia had higher fasting free insulin concentrations before and after therapy than patients without hyperlipoproteinemia and may have a slightly reduced hypoglycemic response to glyburide therapy. The drug caused a significant reduction in very-low-density lipoprotein cholesterol in patients with non-insulin-dependent diabetes mellitus and type IV hyperlipoproteinemia, along with a variable change in high-density lipoprotein cholesterol, independent of its effect on plasma glucose.
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PMID:Effects of glyburide therapy on lipoproteins in non-insulin-dependent diabetes mellitus. 393 66

The existence of [Ca2+]i-activated K+-channels in the pancreatic beta-cell membrane is based in two observations: quinine inhibits K+-permeability and, increasing intracellular Ca2+ stimulates it. The changes in K+-permeability of the beta-cell have been monitored electrically by combining measurements of the dependence of the membrane potential on external K+ concentration and input resistance. The changes in the passive 42K and 86Rb efflux from the whole islet have been measured directly. Intracellular Ca2+ has been increased by various means, including increasing extracellular Ca2+, addition of the Ca2+-ionophore A23187 or noradrenaline and application of mitochondrial uncouplers and blockers. In addition to quinine, many other substances have been found to inhibit or modulate the [Ca2+]i-activated K+-channel. The most important of these is the natural stimulus for insulin secretion, glucose. Glucose may inhibit K+-permeability by lowering intracellular Ca2+. Glibenclamide, a hypoglycaemic sulphonylurea, is about 25 times more active than quinine in blocking the K+-channel in beta-cells. The methylxanthines, c-AMP, various calmodulin inhibitors and Ba2+ also inhibit K+-permeability. Genetically diabetic mice have been studied and show an alteration in the [Ca2+]i-activated K+-channel. It is concluded that the [Ca2+]i-activated K+-channel plays a major role in the normal function of the pancreatic beta-cell. The study of its properties should prove valuable for the understanding and treatment of diabetes.
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PMID:Properties of the Ca-activated K+ channel in pancreatic beta-cells. 632 7

Previous in vivo findings indicated that alpha-adrenergic blocking agents enhanced tolbutamide-induced insulin secretion, whereas beta-blockade attenuated it. In the present study, the interaction of tolbutamide and glyburide with the rat islet adrenergic receptors is examined directly by determining the effectiveness of these drugs to displace the specific alpha- and beta-adrenergic radioligands, [3H]-clonidine and [3H]-dihydroalprenolol (DHA). It was found that both tolbutamide and glyburide had affinity constants for the adrenergic receptors that were similar to those for the natural receptor ligands and powerful antagonists. Tolbutamide displaced both alpha- and beta-radioligands but had a higher affinity at the beta-receptor. Glyburide also displaced radioligands from both types of receptors but had a higher affinity for the alpha-receptor. This study suggests that these two sulfonylurea hypoglycemic agents may affect insulin secretion by different mechanisms.
Diabetes 1984 May
PMID:Tolbutamide and glyburide differ in effectiveness to displace alpha- and beta-adrenergic radioligands in pancreatic islet cells and membranes. 632 36


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