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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is induced under diabetic conditions and possibly causes various forms of tissue damage in patients with diabetes. Recently, it has become aware that susceptibility of pancreatic beta-cells to oxidative stress contributes to the progressive deterioration of beta-cell function in type 2 diabetes. A hypoglycemic sulfonylurea, gliclazide, is known to be a general free radical scavenger and its beneficial effects on diabetic complications have been documented. In the present study, we investigated whether gliclazide could protect pancreatic beta-cells from oxidative damage. One hundred and fifty microM hydrogen peroxide reduced viability of mouse MIN6 beta-cells to 29.3%. Addition of 2 microM gliclazide protected MIN6 cells from the cell death induced by H(2)O(2) to 55.9%. Glibenclamide, another widely used sulfonylurea, had no significant effects even at 10 microM. Nuclear chromatin staining analysis revealed that the preserved viability by gliclazide was due to inhibition of apoptosis. Hydrogen peroxide-induced expression of an anti-oxidative gene heme oxygenase-1 and stress genes A20 and p21(CIP1/WAF1), whose induction was suppressed by gliclazide. These results suggest that gliclazide reduces oxidative stress of beta-cells by H(2)O(2) probably due to its radical scavenging activity. Gliclazide may be effective in preventing beta-cells from the toxic action of reactive oxygen species in diabetes.
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PMID:Gliclazide protects pancreatic beta-cells from damage by hydrogen peroxide. 1264 74

Atherosclerotic cardiovascular disease is the leading cause of premature death in patients with diabetes. Atherosclerosis is a chronic immune-mediated disease, the initiation, progression, and destabilization of which is driven and regulated by inflammatory cells. One critical event in the initiation of this vascular inflammatory disease is the adhesion of leukocytes to the activated endothelium and their migration into the vessel wall. These processes are mediated by the upregulation of adhesion molecules on endothelial cells (ECs) and an increased expression in the vascular wall of chemotactic factors to leukocytes. Monocyte binding to ECs is increased in diabetes. One major determinant of this alteration could be oxidative stress. Given the free-radical scavenging activity of gliclazide, we determined the ex vivo and in vitro effects of this drug on human monocyte binding to ECs and the molecular mechanisms involved in this effect. Our results demonstrate that short-term administration of gliclazide to patients with type 2 diabetes normalizes the levels of plasma lipid peroxides and monocyte adhesion in these subjects. Gliclazide (10 microg/mL) also reduces oxidized low-density lipoprotein (oxLDL)- and advanced glycation end product (AGE)-induced monocyte adhesion to ECs in vitro. The inhibitory effect of this drug on AGE-induced monocyte adhesion involves a reduction in EC adhesion molecule expression and inhibition of nuclear factor kappaB (NF-kappaB) activation. In addition, gliclazide inhibits oxLDL-induced monocyte adhesion to cultured human aortic vascular smooth muscle cells (HASMCs) in vitro and reduces the production of monocyte chemotactic protein-1 (MCP-1) by these cells. Taken collectively, these results show that gliclazide, at concentrations in the therapeutic range, inhibits ex vivo and in vitro monocyte adhesiveness to vascular cells. By doing so, this drug could reduce monocyte recruitment into the vessel wall and thereby contribute to attenuating the sustained inflammatory process that occurs in the atherosclerotic plaque. These findings suggest that treatment of diabetic patients with this drug may prevent or retard the development of vasculopathies associated with diabetes.
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PMID:Benefits of gliclazide in the atherosclerotic process: decrease in monocyte adhesion to endothelial cells. 1293 34

Gliclazide modified release that has been recently launched by Servier (Uni Diamicron 30 mg) is a new formulation of gliclazide to be given once daily. The original hydrophilic matrix improves the biodisponsibility of gliclazide and allows a progressive release of the drug that better parallels the 24-hour glycaemic profile of patients with type 2 diabetes mellitus. Such characteristics may explain the rather low risk of hypoglycaemic episodes and the morning administration should contribute to improve patient's compliance. As the common formulation of gliclazide, the modified release formulation is indicated in the treatment of type 2 diabetes, in adult subjects, when diet, exercise and weight loss are insufficient to restore an adequate metabolic control. It may be used alone or in combination with metformin, glitazones, acarbose or insulin, with the same general principles of use as for the classical formulation of gliclazide.
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PMID:[Medication of the month. Gliclazide modified release (Uni Diamicron)]. 1467 26

The progression of diabetes and hypertension complications is associated with microalbuminuria. Intensive glycemic control prevents or retards microalbuminuria in patients with type 2 diabetes, but little is known about the respective benefits of different antidiabetic drugs. We studied the effect of gliclazide and pioglitazone on microalbuminuria in patients with type 2 diabetes. We excluded patients with very poor glycemic control (glycated hemoglobin [HbA(1c)] >10%), impaired liver function, nondiabetic renal diseases, and those whose urine contained red blood cells, hemoglobin, or casts. Each patient received the designated drug for 12 weeks and their body weight, blood pressure (BP), fasting plasma glucose (FPG), HbA(1c), lipids (triglycerides [TG], total, and high-density lipoprotein-cholesterol [HDL-C]), 1,5 anhidroglucitol (1,5-AG), immunoreactive insulin (IRI), and urinary albumin to creatinine ratio (UACR) were measured every month. The effects of the drugs were analyzed using 2-way repeated measures analysis of variance (ANOVA). The 2 groups of patients were well matched for age, duration of diabetes, retinal status, blood pressure, body mass index (BMI), IRI, FPG, HBA(1c), 1,5-AG, lipids, and UACR, as well as the use of antihypertensive drugs. After treatment, no significant differences were seen in drug efficacy between the 2 groups. Gliclazide and pioglitazone significantly reduced FPG (F = 26.0, P <.0001), HBA(1c) (F = 48.1, P <.0001), and total cholesterol (TC) levels (F = 3.5, P <.05). Decrements in these metabolic parameters were comparable between the groups. 1,5-AG increased in both groups (F = 27.5, P <.0001), and the increment was comparable in both groups. Gliclazide and pioglitazone significantly reduced UACR (F = 15.7, P <.0001) with a comparable decrement in both groups. No other variables changed significantly throughout the 12-week treatment. These results suggest that 12 weeks of treatment with gliclazide or pioglitazone are equally effective in reducing microalbuminuria with similar improvements in blood glucose and cholesterol levels, independent of their mechanisms of actions.
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PMID:Effect of antidiabetic medications on microalbuminuria in patients with type 2 diabetes. 1501 49

Sulphonylureas (SUs) act by inhibition of beta-cell K(ATP) channels after binding to the sulphonylurea receptor SUR1. K(ATP) channels are also expressed in cardiac and vascular myocytes coupled to SUR2A and SUR2B involved into adaptations of vascular tone and myocardial contractility. Different influence of SUs on vascular function is based on different binding to the SUR family. Few data on the effect of different SUs, used in patients in therapeutic doses, on vascular function are currently available. We investigated possible effects of acute and chronic treatment with glibenclamide and gliclazide on forearm postischaemic reactive hyperaemia (RH) in type 2 diabetic patients. To that purpose a double-blind, randomized, cross-over study with gliclazide (80 mg, b.i.d.) and glibenclamide (5 mg, b.i.d.) was performed in 15 type 2 diabetic patients. Forearm vascular reactivity was measured after 5 min of ischaemia by plethysmography before and after 4 weeks treatment. After acute administration of gliclazide (80 mg) or glibenclamide (5 mg) RH was not influenced. After 4 weeks of treatment, no influence of either drug was seen in the steady state before dosing. After dosing glibenclamide induced a significant (P = 0.004) reduction of RH from 26.4 +/- 6.9 to 21.9 +/- 7.6 ml min(-1)/100 ml after 4 h. Gliclazide, conversely, did not induce a reduction of RH (23.9 +/- 6.0 to 23.3 +/- 6.6 ml min(-1)/100 ml). No influence of HbA1c or actual glycaemia on RH was observed. Our results indicate that in chronically treated patients with type 2 diabetes ingestion of glibenclamide but not gliclazide results in sustained reduction of postischaemic RH. This difference is most probably based on different SUR binding.
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PMID:Forearm vascular reactivity is differentially influenced by gliclazide and glibenclamide in chronically treated type 2 diabetic patients. 1565 79

Gliclazide is a well known agent used for NIDDM. Present paper reports the synthesis and characterization of its metal complexes with magnesium, calcium, chromium, manganese, iron, nickel, copper, zinc and cadmium. These complexes were characterized through physical characteristics, IR, H(1)-NMR, and atomic absorption spectroscopic studies.
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PMID:Synthesis and characterization of gliclazide complexes of magnesium, calcium, chromium, manganese, iron, nickel, copper, zinc and cadmium salts. 1638 Mar 56

Gliclazide is the most commonly used sulfonylurea derivative for NIDDM therapy. Due to its prolonged therapy, there is always a likelihood of its use with other drugs. On the other hand antacids are commonly prescribed to encounter gastric acidity etc. Present paper deals with the in vitro availability studies of gliclazide in presence of antacids. These studies were carried out in simulated gastric juice and in buffer of pH 7.4 at body and accelerated temperature. The antacids used in these studies were aluminum hydroxide, aluminum trisilicate, magnesium oxide, magnesium trisilicate, sodium bicarbonate, calcium carbonate, magaldrate and simethicone (2,4-dimethoxypoly-siloxane). It has been found that in case of magnesium oxide, magnesium trisilicate and sodium bicarbonate, availability of gliclazide was enhanced while in rest of the antacids retarded the availability of gliclazide.
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PMID:In vitro availability of gliclazide in presence of antacids. 1641 65

Several factors influence diabetes control, and many of these can adversely affect endeavors to obtain optimal glycemic management. For many patients with type 2 diabetes mellitus, the passage of time often results in a loss of responsiveness to medication and a greater difficulty in achieving desired target levels. Although these observations in part reflect a natural progression of diabetes, irrespective of treatment given, it is possible to identify modifiable hurdles that can be addressed with better outcome results. Lifestyle measures, particularly diet and exercise, remain paramount, whereas other secondary confounding factors such as systemic or endocrine disease or other conflicting medication need specific therapeutic attention. Most patients with type 2 diabetes mellitus will require oral hypoglycemic medication and this should be prescribed in the simplest, most effective, and safest way. Ensuring that patients fully understand treatment objectives is important resulting in better compliance with advised treatment. Such compliance can be significantly improved by keeping treatment regimens simple. With its novel once-daily formulation, gliclazide modified release has been shown to improve adherence to medication and result in better glycemic outcome as determined by improved HbA(1c) levels. Its benefits in terms of reduced risk of hypoglycemia have been demonstrated in the GlUcose control In type 2 diabetes: Diamicron modified release versus glimEpiride study.
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PMID:Overcoming the hurdles to achieving glycemic control. 1663 8

Type 2 diabetes mellitus is associated with increased oxidative stress. Free radicals produced during this stress may damage various cellular components. Gliclazide, a second-generation sulfonylurea, is an oral hypoglycemic drug that possesses antioxidant properties. Therefore, gliclazide may diminish the harmful consequences of oxidative stress in diabetic patients. The aim of our study was to evaluate the action of gliclazide on DNA damage and repair in normal human peripheral blood lymphocytes and insulinoma mouse cells (beta-TC-6). DNA damage and repair were induced by hydrogen peroxide, gamma and ultraviolet radiation and MNNG (N-methyl-N'-nitro-N-nitrosoguanidine) in the presence or absence of gliclazide and were analysed by the alkaline comet assay. DNA double-strand breaks were assayed by pulsed-field gel electrophoresis. Gliclazide protected DNA of both kinds of cells from DNA damage induced by chemicals and radiations. These results suggest that gliclazide may diminish the risk of free radical-related diseases associated with type 2 diabetes mellitus and possibly cancer.
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PMID:Effect of gliclazide on DNA damage in human peripheral blood lymphocytes and insulinoma mouse cells. 1696 9

Gliclazide, a second-generation sulfonylurea, has anti-oxidant properties as well as hypoglycemic activities. In the present study, we investigated whether gliclazide affected proliferation and/or differentiation of HW white and HB2 brown adipocyte cell lines. Gliclazide inhibited proliferation of HW and HB2 cells in the medium containing fetal calf serum or epidermal growth factor (EGF). Gliclazide inhibited phosphorylation of EGF receptor and of extracellular signal-regulated kinase (ERK) 1/2 stimulated by EGF. Gliclazide increased lipid accumulation and peroxisome proliferator-activated receptor gamma (PPARgamma) expression in the early stage of differentiation of adipocytes. A K(ATP) channel activator, diazoxide, did not inhibit the increase of lipid accumulation by gliclazide. Furthermore, gliclazide inhibited the DNA-binding activity of PPARgamma in mature adipocytes. On the other hand, glibenclamide, other sulfonylurea, did not show these effects. These results indicate gliclazide inhibits proliferation and stimulates differentiation of adipocytes via down-regulation of the EGFR signalling. Gliclazide may have preventive and therapeutic effects on obesity, as well as on type 2 diabetes.
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PMID:Gliclazide inhibits proliferation but stimulates differentiation of white and brown adipocytes. 1796 69


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