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

To clarify whether the effect of sulfonylurea on glucagon secretion is directly on the pancreatic A cell, we examined changes produced by gliclazide in glucagon (IRG), insulin (IRI) and somatostatin (IRS) release from the isolated perfused rat pancreas. Under 5 mM glucose infusion, IRI and IRS were increased by gliclazide in a dose-dependent manner, but IRG was unchanged. When 20 mM arginine was infused to stimulate glucagon secretion, both IRI and IRG increased markedly in a biphasic fashion and IRS increased slightly. The administration of gliclazide at the time of second phase response of IRG, IRI and IRS increased further and IRG decreased at every dose used. Insulin administration to the control and streptozotocin-treated rat pancreas did not change arginine-induced IRG secretion. Gliclazide-induced glucagon suppression was also observed in streptozotocin-diabetic rat pancreas. The amount of administered somatostatin required for inhibiting glucagon secretion was higher than the maximal level obtained from endogenous secretion of somatostatin after gliclazide. Neither cysteamine treatment alone (somatostatin-depleted) nor combined with streptozotocin-treatment (combined depletion of somatostatin and insulin) changed gliclazide-induced glucagon suppression. Thus, it is concluded that suppression of glucagon is induced by sulfonylurea itself.
Diabetes Res Clin Pract 1994 Jul
PMID:Gliclazide directly suppresses arginine-induced glucagon secretion. 798 45

We evaluated insulin resistance and assessed the effect of gliclazide on insulin resistance in a patient with diabetes mellitus associated with Turner's syndrome. Insulin-induced glucose metabolism markedly decreased compared with 12 healthy subjects. The insulin dose-response curve of this patient shifted to the right and down, and recovered somewhat after the administration of gliclazide. This patient had exhibited marked insulin resistance, which seemed to be caused by a defect at the receptor and/or post-receptor levels. Gliclazide reduced her insulin resistance, which suggests that this agent is suitable for treating the insulin resistance in diabetic patients with Turner's syndrome.
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PMID:Insulin resistance in a patient with diabetes mellitus associated with Turner's syndrome. 800 Jan 10

A postmarketing study involving 114 office practices provides the largest body of clinical experience to date in Canada with the second-generation sulfonylurea gliclazide in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). This study focused on efficacy and safety in 411 NIDDM patients. Subjects included patients whose disease was not controlled by diet alone or by diet plus an antidiabetic drug. The dose of gliclazide was 80 mg/day to 320 mg/day. Patients were treated for 3 months, with monthly evaluations. Fasting and 2-hour blood glucose and glycated hemoglobin levels were measured before and after the study period, with all values showing a significant decrease (P = 0.01). Total cholesterol and triglyceride levels also decreased significantly during the study (P = 0.05). Adverse effects were recorded in 30 (7.3%) of patients and led to the withdrawal of 1.2% from the study. Hypoglycemia symptoms were less frequently encountered with gliclazide than with previous treatments (P = 0.001). Gliclazide was found to be safe and well tolerated in the majority of patients. The results of this study appear to confirm the established efficacy of gliclazide in treating NIDDM.
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PMID:Efficacy and safety of gliclazide in the treatment of non-insulin-dependent diabetes mellitus: a Canadian multicenter study. 811 3

The estimation of the influence of gliclazide and gliquidone treatment on platelet function in type II diabetic patients was undertaken in the study. Aggregation parameters were assessed before and after the change of hypoglycemic therapy. Gliclazide was applied in the group I (11 patients, mean age 63.1 +/- 7.22 years, duration of diabetes 5.63 +/- 2.98 years), group II (19 patients, mean age 58.3 +/- 12.4 years, duration of diabetes 7.1 +/- 2.4) received gliquidone. The reference group consisted of 10 healthy volunteers (mean age 51.7 +/- 6.9). Aggregation parameters (threshold ADP concentration, intensity and velocity of the aggregation) were measured in examined groups of subjects. Metabolic control was estimated basing upon spectrophotometric measurement of fructosamine level. Significant increase in threshold ADP concentration (1.89 +/- 0.47 mumol/l before and 2.36 +/- 0.58 mumol/l after the treatment change p < 0.05) in group II was found. Threshold ADP concentration did not change significantly in group I (2.5 +/- 0.8 mumol/l before v 2.14 +/- 0.68 mumol/l after treatment). Significant decrease in the aggregation intensity was found in both groups (in group I 8.48 +/- 1.7 before v 6.39 +/- 2.17 after; in group II 7.35 +/- 1.73 before v 6.05 +/- 1.6 after 1 month treatment--both p < 0.05). The aggregation velocity did not change significantly (group I 61. +/- 11 before v 51.3 +/- 18.7 after, group II 63.2 +/- 14.8 and 62.8 +/- 13.7 respectively). Reference group values were ADP 2.7 +/- 0.16, intensity 6.22 +/- 0.53, velocity 63.2 +/- 2.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Does hypoglycemic treatment with gliclazide and gliquidone affect platelet function in type II diabetic patients?]. 835 Dec 32

Diabetes affects at least 20% of the population over the age of 65. Half of these patients are unaware that they have the disease. Diabetes in middle-aged subjects is characterized by an impairment in glucose induced insulin release, increased fasting hepatic glucose output and resistance to insulin mediated glucose disposal. In contrast, diabetes in the elderly is primarily associated with insulin deficiency. The presentation of diabetes in the aged is often non-specific. The elderly have an increased frequency of complications from diabetes. They are particularly susceptible to hypoglycaemia, because of reduced awareness of hypoglycaemic warning symptoms and altered release of counterregulatory hormones. Although no data are yet available from randomized controlled trials, there is abundant epidemiological evidence to suggest that adequate control of blood glucose can be expected to reduce the risk of long-term complications. A team approach is ideal for the management of the elderly patient with diabetes. Little data is available on which to base a diet and exercise prescription for elderly patients. Gliclazide appears to be the sulphonylurea of choice in the aged because it is associated with a lower frequency of hypoglycaemic reactions. Urine glucose testing is unreliable, and capillary glucose monitoring is preferred. Fructosamine may prove to be superior to haemoglobin A1C for monitoring long-term control.
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PMID:Diabetes in the elderly. 886 56

Gliclazide interferes with the glucose determination using the glucose oxidase/peroxidase (EC 1.1.3.4/1.11.1.7) (GOD-PERID) method utilizing 2,2-azino-di-(3-ethyl-benzothiazoline-6-sulphonic acid) (ABTS) as the oxygen acceptor chromogen. There was an essentially linear relationship between the concentrations of gliclazide and decreasing glucose readings. One mu mol/1 of gliclazide in samples leads to an apparent loss of about 2.5 mu mol/l of glucose. However, gliclazide did not interfere with the glucose determination using the hexokinase/glucose-6-phosphate dehydrogenase method. This interference in the GOD-PERID method for glucose assay can occur in the in vitro experimental samples and cause underestimation of the glucose values. It is suggested that careful attention should be paid to the limited applicability of the GOD-PERID method for glucose assay.
Diabetes Res Clin Pract 1995 Nov
PMID:Interference by gliclazide in the glucose oxidase/peroxidase method for glucose assay. 883 37

The mechanism of the hypoglycemic action of gliclazide was evaluated in 17 diet-treated non-insulin-dependent diabetes mellitus (NIDDM) patients. In study A, five patients received a 240-minute glucose infusion along with [3-3H]glucose infusion. In study B, seven patients received a 240-minute isoglycemic insulin clamp along with [3-3H]glucose infusion. And in study C, five patients received a somatostatin infusion with basal replacing doses of insulin and glucagon. The three studies (A, B, and C) were repeated twice. Gliclazide (240 mg orally) was administered on one occasion, and placebo was given on the second occasion. Basal hepatic glucose production (HGP) and utilization and plasma glucose, insulin, C-peptide, glucagon, and free fatty acid (FFA) concentrations were similar before administration of gliclazide and placebo. In study A, plasma glucose, its incremental area, and HGP were reduced by gliclazide administration (all P < .05), but glucose utilization was not significantly affected. The increase in plasma insulin and C-peptide concentrations was similar with gliclazide and placebo, although the plasma insulin to glucose ratio was increased with gliclazide. HGP decremental area was correlated with the reduction in plasma glucose incremental area (r = -.63, P < .05). In study B, gliclazide administration produced a larger suppression of HGP, but the overall rate of glucose utilization was not different in the two studies. In study C, plasma glucose concentration and HGP progressively decreased in both studies, without a difference between gliclazide and placebo. These results suggest that under conditions of hyperglycemia and hyperinsulinemia gliclazide elicits a larger suppression of HGP.
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PMID:Gliclazide potentiates suppression of hepatic glucose production in non-insulin-dependent diabetic patients. 884 72

We investigated therapeutic effects of a rapid- and short-acting non-sulfonylurea hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate (KAD-1229), on streptozotocin (STZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. The effects exerted by KAD-1229 on the post-prandial plasma glucose rise in STZ-induced mild NIDDM (mNIDDM) rats were different from those of sulfonylureas. When KAD-1229 with liquid meal (10 kcal/kg) was given to the mNIDDM rats, the plasma glucose migration was similar to that of normal healthy rats. On the contrary, glibenclamide had little or no effect on the plasma glucose rise 0.5-1 hr after oral administration, and its effect was only evident 2-5 hr after dosing. Tolbutamide showed similar hypoglycemia to that induced by glibenclamide at 2-5 hr with insufficient efficacy at 0.5 hr. Gliclazide sufficiently suppressed the level of post-prandial plasma glucose. However, its complete inhibition of post-prandial plasma glucose was associated with the extra-hypoglycemia 1-5 hr after oral administration. We also tested the efficacy of KAD-1229 in more severe STZ-induced NIDDM (sNIDDM) rats to elucidate the effects of the drug on the long-term glycemic controls and diabetic complications. When the sNIDDM rats were treated with 10 mg/kg KAD-1229 twice a day for about 17 weeks, increases in fasting plasma glucose and hemoglobin A1c were inhibited. Furthermore, treatment with KAD-1229 suppressed the development of microalbuminuria and cortical cataract. We conclude that the rapid- and short-acting insulinotropic agent KAD-1229 is able to improve the deterioration in the glycemic controls and inhibit the development of diabetic complications in STZ-induced NIDDM rats.
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PMID:A rapid- and short-acting hypoglycemic agent KAD-1229 improves post-prandial hyperglycemia and diabetic complications in streptozotocin-induced non-insulin-dependent diabetes mellitus rats. 888 29

The role of reactive oxygen species in diabetes and its complications are well known. Two therapeutic agents commonly used in the treatment of diabetes are the sulfonylureas, gliclazide and glibenclamide. These drugs effectively reduce blood sugar in non-insulin dependent diabetes millitus by augmenting insulin release. Gliclazide is known to be a general free radical scavenger as demonstrated by inhibition of o-dianisidine photo-oxidation. In this study, the effects of gliclazide and glibenclamide on free radicals were examined in vitro, using electron spin resonance (ESR) spectroscopy. Superoxide radical (O2.-) generated from hypoxanthine-xanthine oxidase system, or hydroxyl radical (.OH) generated by the Fenton reaction, were analyzed as spin adducts of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). NO was generated from 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7), and analyzed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl (carboxy-PTI) produced from the reaction between 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO) and NO. Gliclazide scavenged O2.-, .OH and NO in a dose-dependent manner whereas glibenclamide was without effect. These findings suggest that gliclazide is not only effective in reducing blood sugar but also may be beneficial by inhibition of lipid and protein denaturation, which leads to the development of diabetic complications.
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PMID:Gliclazide scavenges hydroxyl, superoxide and nitric oxide radicals: an ESR study. 922 46

Low-density lipoprotein (LDL) oxidation has been suggested to play a key role in the pathogenesis of atherosclerosis, a major complication of diabetes mellitus. Gliclazide, a second-generation sulfonylurea, is widely used in the treatment of type II diabetes mellitus. Recently, a free-radical-scavenging activity of gliclazide has been reported. In the present study, we examined the effects of gliclazide on cell-mediated LDL oxidation and monocyte adhesion to endothelial cells induced by oxidatively modified LDL. Incubation of human monocytes and bovine aortic endothelial cells (BAE cells) with increasing concentrations of gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) resulted in a dose-dependent diminution of cell-mediated LDL oxidation as assayed by measurement of thiobarbituric acid (TBA)-reactive substances (TBARS). In addition, exposure of BAE cells to gliclazide (0 to 10 micrograms/mL) and native LDL (100 micrograms/mL) induced a dose-dependent diminution of the oxidized LDL-induced monocyte adhesion to BAE cells as measured by the myeloperoxidase (MPO) assay. The effects of glyburide, another second-generation sulfonylurea, were also tested on cell-mediated oxidation of LDL and LDL-induced monocyte adhesion to the endothelium. No significant effect of this drug was observed on these two processes. These results therefore demonstrate that gliclazide is effective in vitro in reducing both cell-mediated LDL oxidation and monocyte adhesion to the endothelium. These findings suggest a potential beneficial effect of gliclazide in the prevention of atherosclerosis in diabetic patients.
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PMID:Gliclazide decreases cell-mediated low-density lipoprotein (LDL) oxidation and reduces monocyte adhesion to endothelial cells induced by oxidatively modified LDL. 932 98


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