Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new glyburide research articles will be listed here shortly after becoming available to us.
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Medical research on glyburide
Relaxing effects of 17(18)EpETE on arterial and airway smooth muscles in human lung.
Am J Physiol Lung Cell Mol Physiol. 2008 Oct 31;
Morin CS, Sirois M, Echave V, Rizcallah E, Rousseau E
Human cytochrome P-450 epoxygenase enzymes metabolize eicosapentaenoic acid (EPA), an omega3-poly unsaturated fatty acid (PUFA), and leads to the production of 17(18)-epoxyeicosatetraenoic acid or 17(18)-EpETE. The aim of the present study was to delineate the mode of action of 17(18)-EpETE on human pulmonary artery (HPA) and distal bronchi. Isometric tension measurements demonstrated that 17(18)-EpETE induced concentration-dependent relaxing effects in pulmonary artery and airway smooth muscles. Iberiotoxin (IbTx) and Glyburide (Glyb), known BKCa and KATP channel inhibitors respectively, reversed the relaxation induced by 17(18)-EpETE on both tissues types. Microelectrode measurements showed that exogenous addition of 17(18)-EpETE hyperpolarized the membrane potential of HPA and bronchial smooth muscle cells. These induced electrophysiological effects were reversed by the addition of 10 nM IbTx and 10 microM Glyb. Complementary experiments performed on human bronchi, using the planar lipid bilayer reconstitution technique, demonstrated that 17(18)-EpETE activated reconstituted BKCa channels at low free Ca(2+) concentration. Moreover in bronchi, the relaxing responses induced by 17(18)-EpETE were also related to reduced Ca(2+) sensitivity of the myofilaments, since free Ca(2+) concentration-response curves, performed on beta-escin permeabilized cultured explants, were shifted toward higher [Ca(2+)]. Together these results provide new insight into the mode of action of 17(18)-EpETE in lung tissues and highlight this eicosanoid as a potent modulator of tone on both HPA and distal bronchi in vitro, which may be of clinical relevance in the pathophysiology of pulmonary hypertension and airway diseases. Key words: 17(18)-eicosatetraenoic acid, pulmonary arteries, bronchi, membrane potential.
J Pediatr Endocrinol Metab. 2008 Sep; 21(9): 895-903
Begum-Hasan J, Polychronakos C, Brill H
We describe 3 years follow-up of glyburide therapy in a child with permanent neonatal diabetes mellitus (PND) born to a 19 year-old mother with congenital diabetes mellitus. Genetic analysis identified a KCNJ11 mutation (R201H) in both the child and her mother. After 2 years of insulin therapy, the patient was switched to oral glyburide. After initial stabilization, glyburide therapy resulted in a marked decrease in glucose excursions in comparison to insulin. The patient had 3-10 episodes of hypoglycemia per week, including a total of eight episodes resulting in seizures, while on insulin. In contrast, no severe hypoglycemia was reported on glyburide. The patient's basal C-peptide was undetectable on insulin therapy (< 166 pmol/l) but was easily detectable on glyburide (189-761 pmol/l). The range of HbA1c improved significantly from 8-12% on insulin to 4.7-6% on glyburide. The frequency of glucose monitoring was gradually decreased from 4-8 times to 2-3 times a day on oral glyburide. This report confirms the superiority of sulfonylurea therapy in the treatment of PND with Kir6.2 mutations and shows sustained improved glycemic control over a 3-year follow-up period. Genetic exploration in other family members with diabetes might provide further insight into the nature of familial neonatal diabetes.
J Obstet Gynaecol. 2008 Jul; 28(5): 485-9
Gedeon C, Anger G, Lubetsky A, Miller MP, Koren G
Glyburide, a drug used to treat gestational diabetes has previously been shown not to be measurable in fetal blood, and to be transferred from the fetal to the maternal circulation against a concentration gradient. The objective of the study is to determine whether indomethacin, an inhibitor of the multi-drug resistance family (MRP) of transporters is involved in the active efflux of glyburide from the fetus to the mother. Using the dually perfused human placental cotyledon model, 12 perfusions were performed of both glyburide and indomethacin concomitantly. The rate of transfer of glyburide in the presence of inhibitor was not different from the rate of transfer of glyburide in the absence of inhibitor. Furthermore, our study suggests that MRP1, 2 or 3 may be only minimally involved in the transport of glyburide across the human placenta. These results pose other ABC transporters, such as likely candidates for the placental transfer of glyburide.
Clin Pharmacol Ther. 2008 Oct 8;
Zheng H, Huang Y, Frassetto L, Benet L
The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.Clinical Pharmacology & Therapeutics advance online publication 08 October 2008. doi:10.1038/clpt.2008.186.
Can J Cardiol. 2008 Oct; 24(10): e65-9
Gupta M, Braga MB, Verma S
BACKGROUND: Although rosiglitazone may offer vascular benefits beyond lowering glucose, recently, concern has been raised that this drug may paradoxically increase cardiovascular risk. OBJECTIVE: To assess the effects of rosiglitazone compared with standard oral hypoglycemic therapies on adipokines, and inflammatory and fibrinolytic markers in subjects with type 2 diabetes. METHODS: A 12-week, randomized, open-label, parallel-group study will be conducted on 100 type 2 diabetic subjects with suboptimal glycemic control (glycosylated hemoglobin 0.075 or greater) despite management with lifestyle alone (drug-naive) or with monotherapy (either metformin or sulfonylurea). Drug-naive patients will be randomly assigned to receive either rosiglitazone (4 mg/day to 8 mg/day) or metformin (500 mg/day to 2000 mg/day). Patients on pre-existing monotherapy will be randomly assigned to the addition of rosiglitazone (4 mg/day to 8 mg/day), or to either metformin (500 mg/day to 2000 mg/day) or glyburide (5 mg/day to 20 mg/day) (depending on background treatment). The primary end point of the study is the change in adiponectin level (from baseline to 12 weeks) in the rosiglitazone versus metformin or sulfonylurea arms. Secondary end points include changes in leptin, high-sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-alpha, matrix metalloproteinase-9, vascular cell adhesion molecule-1, plasminogen activator inhibitor type 1, insulin sensitivity, glycosylated hemoglobin and lipid levels. Additionally, all patients will be required to be treated with an inhibitor of the renin-angiotensin system, namely an angiotensin receptor antagonist, as per national diabetes treatment guidelines, to a target systolic blood pressure of less than 130 mmHg and a diastolic blood pressure of less than 80 mmHg, or for the optimal suppression of microalbuminuria.
Shock. 2008 Oct 6;
O'Brien A, Stidwill RP, Clapp LH, Singer M
Excess production of NO and activation of vascular ATP-sensitive potassium (KATP) channels are implicated in the hypotension and vascular hyporeactivity associated with endotoxic shock. Using a fluid-resuscitated endotoxic rat model, we compared the cardiovascular effects of an iNOS inhibitor and two distinct inhibitors of the KATP channel. Endotoxin (LPS) was administered to anesthetized, spontaneously breathing, fluid-resuscitated adult male Wistar rats, in which MAP, aortic and renal blood flow, and hepatic microvascular oxygenation were monitored continuously. At 120 min, the iNOS inhibitor, GW273629, and the KATP-channel inhibitors, PNU-37883A and glyburide, were administered separately, and their effects on hemodynamics and oxygenation were examined. We found that GW273629 increased MAP over and above the pressor effect achieved in sham animals. Inhibiting KATP channels via the pore-forming subunit (PNU-37883A and high-dose glyburide) produced significant pressor effects, whereas inhibiting the sulfonylurea receptor with low-dose glyburide was ineffective. No agent reversed the fall in aortic or renal blood flow, the fall in hepatic microvascular oxygenation, or the metabolic acidosis that occurred in LPS-treated animals. We conclude that inhibition of the KATP channel via the pore-forming, but not the sulfonylurea receptor subunit, increases blood pressure in a short-term endotoxic model. However, this was not accompanied by any improvement in macrocirculatory or microcirculatory organ blood flow nor reversal of metabolic acidosis. It therefore remains uncertain whether the iNOS pathway or the KATP channel represents a potential target for drug development in the treatment of endotoxic shock.
The effect of protein transport inhibitors on the production of extracellular DNA.
Ann N Y Acad Sci. 2008 Aug; 1137: 31-5
Morozkin ES, Babochkina TI, Vlassov VV, Laktionov PP
The presence of various genomic sequences in the pool of extracellular DNA was studied by cloning and sequencing the DNA eluted from the surface of HeLa cells. Sequences of 19 genes, 10 pseudogenes, and 41 repeated elements were found in 103 clones. Sequences of LINE repeats were found in 17% of the clones; consequently real-time PCR assay for quantification of LINE repeats was chosen to study the influence of protein transport inhibitors on the concentration of free and cell-surface-bound DNA in the cultures of HUVEC and HeLa cells. Treatment of both cell lines with the inhibitors did not interfere with the concentration of extracellular DNA in the growth medium, except for chloroquine, which doubled the concentration of extracellular DNA in HUVEC culture. The treatment of HUVECs with monensin, glyburide, or methylamine decreases the cell-surface-bound DNA concentration by 30, 35, and 19%, respectively. The incubation of HeLa cells with monensin reduces the concentration of cell-surface-bound DNA by 15%; however, the treatment with glyburide increases cell-surface-bound DNA concentration by 50%. The data obtained demonstrate the involvement of vesicular transport in generation of extracellular DNA.
Indian J Physiol Pharmacol. 2008 Jan-Mar; 52(1): 43-52
Bhattacharya SK, Madan M, Mahajan P, Paudel KR, Rauniar GP, Das BP, Roy RK
Type 2 diabetes affects 100 million people throughout the world. Among the various factors implicated in the causation of this disease, the role of leptin, an obesity gene product, is increasingly being investigated. This especially assumes importance in the light of knowledge that obesity confers a minimum of 3-10 fold higher risk of diabetes. This study was planned to investigate the relationship between leptin and insulin levels in type 2 diabetic patients before and after treatment with glibenclamide or glimepiride. 60 type 2 diabetic patients were recruited for the study and were divided into 2 groups-one receiving glimepiride and the other group receiving glibenclamide for duration of 10 weeks. This study demonstrated a highly positive correlation of plasma leptin levels with BMI, plasma insulin and insulin resistance. No gender specific differences were observed in leptin concentrations. The study, however, failed to demonstrate any possible relationship between glycemic control as assessed by blood sugars/ glycosylated hemoglobin (HbAlc) and plasma leptin. The administration of glibenclamide or glimepiride significantly lowered blood glucose levels coupled with a decrease in (HbAlc). Both the drugs increased insulin concentrations. Glibenclamide increased leptin levels but they remained unaltered with glimepiride. Glibenclamide and glimepiride were found to be equally effective in their glucose lowering action. However, the patients receiving glibenclamide experienced higher episode of hypoglycaemic spells than those receiving glimepiride.
Oral glyburide, but not glimepiride, blocks the infarct-size limiting effects of pioglitazone.
Cardiovasc Drugs Ther. 2008 Dec; 22(6): 429-36
Ye Y, Lin Y, Perez-Polo JR, Birnbaum Y
BACKGROUND: Many patients with type 2 diabetes mellitus receive several oral hypoglycemic agents, including sulfonylurea drugs. Intravenous glyburide (Glyb), a sulfonylurea agent, blocks the protective effects of "ischemic" and pharmacologic preconditioning in various animal models without affecting myocardial infarct size when administered alone. However, there are conflicting results when other sulfonylurea drugs are used. Pioglitazone (PIO) reduces infarct size in the rat. We asked whether oral Glyb and glimepiride (Glim) affect the infarct size-limiting effects of PIO. METHODS: Sprague-Dawley rats received 3-day oral treatment with: PIO (5 mg/kg/day); PIO + Glyb (10 mg/kg/day); PIO + Glim (4 mg/kg/day) or water alone (experiment 1) or PIO (5 mg/kg/day) with or without 5-hydroxydecanoate (5HD, 10 mg/kg), a specific mitochondrial ATP-sensitive K+ channels inhibitor, administered intravenously 30 min before coronary artery ligation. PIO, Glyb and Glim were administered by oral gavage. Sugar 5% was added to water to prevent hypoglycemia. Rats underwent 30 min coronary artery occlusion and 4 h reperfusion (n = 6 in each group). Ischemic area at risk was assessed by blue dye and infarct size by triphenyl-tetrazolium-chloride. RESULTS: Body weight and the size of the area at risk were comparable among groups. Infarct size (% of the area at risk) was significantly smaller in the PIO (14.3 +/- 1.1%; p < 0.001) and PIO + Glim (13.2 +/- 0.8%; p < 0.001) groups than in the control group (37.7 +/- 1.2%). Glyb completely blocked the effect of PIO (43.0 +/- 1.7%; p < 0.001). Glim did not affect the protective effect of PIO (p = 0.993). 5HD blocked the protective effect of PIO (infarct size 48.5 +/- 0.8% versus 14.8 +/- 0.6%, respectively; p < 0.0001). In conclusion, the infarct size limiting effects of PIO are dependent on activation of mitochondrial ATP-sensitive K+ channels. Oral Glyb, but not Glim, blocks the infarct size limiting effects of PIO. It is plausible that Glyb affects other pleiotropic effects of PIO and thus may attenuate favorable effects on cardiovascular outcomes. In contrast, Glim does not attenuate the protective effect of PIO.
Geriatr Gerontol Int. 2008 Sep; 8(3): 160-5
Kigawa Y, Oba K, Futami-Suda S, Norose J, Yasuoka H, Suzuki K, Ouchi M, Watanabe K, Suzuki T, Nakano H
AIM: The aim of this study was to evaluate the difference in daily blood glucose profiles between once- and twice-daily regimens of a moderate daily dose of glibenclamide or gliclazide in elderly patients with type 2 diabetes. METHODS: Daily blood glucose profile data were evaluated in 18 elderly type 2 diabetic patients treated with 80 mg/day gliclazide or 5 mg/day glibenclamide as monotherapy. The first daily blood glucose profile of the twice-daily regimen was performed approximately 1 week before hospital discharge, and the second was performed after taking a once-daily regimen for 4-7 days. Plasma glucose and plasma immunoreactive insulin (IRI) concentrations were measured daily at 12 time points: 08.00 (before breakfast); 10.00; 12.00 (before lunch); 14.00; 18.00 (before dinner); 20.00; 0.00; 02.00; 03.00; 04.00; 06.00; and 08.00 hours the next morning. RESULTS: Daily blood glucose profiles and plasma IRI profiles did not differ between the once- and twice-daily regimen groups in either the gliclazide group or the glibenclamide group. Plasma glucose values between midnight and early morning tended to be lower than the 08.00 hours plasma glucose value in the glibenclamide group, but not in the gliclazide group. CONCLUSION: These results suggest that the blood glucose-lowering effects of a once- and twice-daily moderate daily dose of glibenclamide or gliclazide do not differ in elderly type 2 diabetic patients. However, glibenclamide, regardless of the dosage schedule, tends to lower the plasma glucose values between midnight and early morning.