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

The antidiabetic and antioxidant effects of the herbal preparation ADD-199 were investigated in STZ-induced diabetic C(3)H mice and results were compared with two allopathic hypoglycaemic drugs, glibenclamide and metformin. Plasma glucose, insulin and lipids as well as liver glycogen, lipids and lipid peroxidation were measured following treatment for 8 weeks. The results indicated that plasma insulin levels in normal controls at termination were about 76 micromol/L compared to trace levels in untreated diabetic mice. Glibenclamide and ADD-199 increased insulin levels in diabetic mice up to 70% of levels in untreated non-diabetic mice whilst metformin had no effect. Basal plasma glucose levels in diabetic controls (18.8 mM) were reduced to 14.0 mM by 100 mg/kg ADD-199 in <2 weeks compared to 4 and 6 weeks for glibenclamide and metformin, respectively. This hypoglycaemic effect of ADD-199 appeared to be associated with the alkaloidal content of the extract. Treatment with ADD-199 or the hypoglycaemic agents reversed the observed elevation in plasma lipids but increased hepatic glycogen, triacylglycerol and cholesterol levels. Treatment also increased glucose uptake by isolated diaphragms and attenuated hepatic lipid peroxidation. These antihyperglycaemic and antioxidant actions of ADD-199 at a dose of 100mg/kg/day are comparable to those of the maximum daily therapeutic doses of glibenclamide (0.25 mg/kg) and metformin (50 mg/kg). These could explain the basis for use of this plant extract to manage diabetes mellitus (DM).
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PMID:The antidiabetic activity of the herbal preparation ADD-199 in mice: a comparative study with two oral hypoglycaemic drugs. 1565 71

Oxidative stress is currently suggested as a mechanism underlying diabetes and diabetic-related complications. Oxidative stress results from an imbalance between radical-generating and radical-scavenging systems. Many secondary plant metabolites have been reported to possess antioxidant activity. This study was designed to evaluate the potential antioxidative activity of the ethanolic extract from Aloe vera leaf gel in the plasma and pancreas of streptozotocin (STZ)-induced diabetic rats. Glibenclamide was used as a standard reference drug. Oral administration of ethanolic extract at a concentration of 300 mg kg(-1) body weight for 21 days resulted in a significant reduction in fasting blood glucose, thiobarbituric acid reactive substances, hydroperoxides and alpha-tocopherol and significant improvement in ascorbic acid, reduced glutathione and insulin in the plasma of diabetic rats. Similarly, the treatment also resulted in a significant reduction in thiobarbituric acid reactive substances, hydroperoxides, superoxide dismutase, catalase and glutathione peroxidase and significant improvement in reduced glutathione in the pancreas of STZ-induced diabetic rats when compared with untreated diabetic rats. The ethanolic extract appeared to be more effective than glibenclamide in controlling oxidative stress. Thus, this study confirms the ethnopharmacological use of Aloe vera in ameliorating the oxidative stress found in diabetes.
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PMID:Modulatory effects of Aloe vera leaf gel extract on oxidative stress in rats treated with streptozotocin. 1572 Jul 89

Diabetes mellitus is a heterogeneous disorder of glucose intolerance that is generally classified into the following categories: type 1 and type 2 diabetes and gestational diabetes (GDM). Currently, the number of pregnancies complicated by type 2 diabetes and GDM exceed those affected by type 1 diabetes. Numerous studies have established a direct relationship between maternal glycemic control and neonatal outcomes for all types of diabetes. Therefore, modern treatment protocols during pregnancy emphasize strict glycemic control by a combination of diet and medication. Traditionally, insulin therapy has been considered the gold standard for management because of its efficacy in achieving tight glucose control and the fact that it does not cross the placenta. Since GDM and type 2 diabetes are characterized by insulin resistance and relatively decreased insulin secretion, treatment with oral antihyperglycemic agents that target these defects is of potential interest. However, because of concerns regarding transplacental passage and, therefore, the possibility of fetal teratogenesis and prolonged neonatal hypoglycemia, these agents are not currently recommended in pregnancy. There are no randomized controlled trials on which to draw conclusions regarding the teratogenicity of these oral agents. However, most retrospective studies and the published clinical experience have not demonstrated an increased risk of malformed infants among women treated with oral antihyperglycemic agents. Rather, the data indicate that the increased risk for major congenital anomalies appears to be related to maternal glycemic control prior to and during conception. These studies and currently available data on the use of both metformin and sulfonylureas in pregnancy have also failed to demonstrate an increased risk of neonatal hypoglycemia and other neonatal morbidities. To date, there has only been one randomized controlled trial to test the effectiveness and safety of sulfonylurea therapy (glyburide [glibenclamide]) in the management of women with GDM. Both the insulin- and glyburide-treated women were able to achieve satisfactory glucose control and had similar perinatal outcomes. Glyburide was not detected in the cord serum of any infant in the glyburide group. In summary, based on the currently available data, it appears that glyburide could be safely and effectively utilized in the management of GDM. However, more intensive investigation regarding the safety and feasibility of oral agents in pregnancies complicated by type 2 diabetes is necessary. It is important to emphasize that it is the level of metabolic control achieved and not the mode of therapy that is crucial to improving outcomes in these pregnancies.
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PMID:Is there a role for oral antihyperglycemics in gestational diabetes and type 2 diabetes during pregnancy? 1602 9

Use of sulfonylureas in diabetes treatment is based on their insulin-releasing effect on pancreatic beta-cells. Prolonged action is known to degranulate beta-cells, but functional consequences have not been examined at the cellular level. This study investigates influences of in vivo (48-h) and in vitro (24-h) glibenclamide treatment on the functional state of the beta-cell population. Both conditions decreased cellular insulin content by >50% and caused an elevated basal insulin biosynthetic activity that was maintained for at least 24 h after drug removal. Glibenclamide stimulation of basal insulin synthesis was not achieved after a 2-h exposure; it required a calcium-dependent translational activity and involved an increase in the percent activated beta-cells (50% after glibenclamide pretreatment vs. 8% in control cells). The glibenclamide-activated beta-cell subpopulation corresponded to the degranulated beta-cell subpopulation that was isolated by fluorescence-activated cell sorter on the basis of lower cellular sideward scatter. Glibenclamide pretreatment did not alter cellular rates of glucose oxidation but sensitized beta-cells to glucose-induced changes in metabolic redox and insulin synthesis and release. In conclusion, chronic exposure to glibenclamide results in degranulation of a subpopulation of beta-cells, which maintain an elevated protein and insulin synthetic activity irrespective of the presence of the drug and of glucose. Our study demonstrates that the in situ beta-cell population also exhibits a functional heterogeneity that can vary with drug treatment. Glibenclamide induces degranulated beta-cells with a sustained elevated basal activity that might increase the risk for hypoglycemic episodes.
Diabetes 2006 Jan
PMID:Glibenclamide treatment recruits beta-cell subpopulation into elevated and sustained basal insulin synthetic activity. 1638 Apr 79

Type 2 diabetes is associated with decreased levels of the glycosphingolipid sulfatide, as well as a state of low-grade inflammation. Sulfatide is reported to have anti-inflammatory properties in other cell-types. In the present study, the effects of sulfatide on adipokine (adiponectin, TNF-alpha, IL-6, and IL-8) production in human adipose tissue (AT) was investigated in vitro. Isolated human adipocytes and AT cultures were incubated with sulfatide isolated from pig brain [sulfatide containing a variety of fatty acids or isoforms of sulfatide with defined, saturated fatty acids with 16 (C16:0) or 24 (C24:0) carbon atoms]. Adiponectin production was increased 50-80%, by all sulfatide preparations. Only the C16:0 isoform decreased TNF-alpha, IL-6, and IL-8 production 20-30%. The C16:0 sulfatide has been shown to activate potassium channels in beta-cells, and glibenclamide, an ATP-sensitive K+-(KATP) channel blocker, reversed the C16:0-induced decrement in stimulated TNF-alpha, IL-6, and IL-8 release in adipocytes. Glibenclamide on its own was without effect on the production of adiponectin, TNF-alpha, IL-6, and IL-8. In conclusion, this study shows that, sulfatide exerts anti-inflammatory effects in human adipocytes and AT in vitro. Accordingly, the reported low serum levels of sulfatide in patients with type 2 diabetes might be of importance in relation to the chronic low-grade inflammatory state found in this disease.
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PMID:Sulfatide increases adiponectin and decreases TNF-alpha, IL-6, and IL-8 in human adipose tissue in vitro. 1709 22

Free radical-induced lipid peroxidation has been associated with numerous disease processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses the conjugation of glutathione with a variety of organic peroxides to form more water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential to control intracellular reductive potential by increasing glutathione intracellular levels, which in turn decrease the amount of reactive oxygen species. Glyburide decreases glucose production and enhances insulin action in liver. The aim of this study was to examine the effects of glyburide on the antioxidant enzyme activities in the liver tissue of diabetic rat. We investigated the activities of GST and G6PDH in the liver of both control and streptozotocin-induced diabetic rats. Forty male albino rats were included in this study. Liver GST and G6PDH activities decreased significantly in five-week diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration suggest that glyburide may directly alter hepatic enzyme activities.
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PMID:The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose-6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver. 1721 64

We have investigated the possible antihyperglycaemic effects of Sphaeranthus indicus extract in rats rendered diabetic by nicotinamide (120 mgkg(-1) i.p.) and streptozotocin (STZ) (60 mgkg(-1) i.p). Fasting plasma glucose levels, serum insulin levels, serum lipid profiles, magnesium levels, glycosylated haemoglobin, changes in body weight and liver glycogen levels were evaluated in normal and diabetic rats. Oral administration of S. indicus for 15 days resulted in significant decrease in blood glucose levels and increases in hepatic glycogen and plasma insulin levels. Fasting normal rats treated with the alcoholic extract of S. indicus showed significant improvement in oral glucose tolerance test. Glibenclamide was used as a reference standard. The findings demonstrate that the alcoholic S. indicus extract may be useful in the treatment of diabetes.
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PMID:Antidiabetic properties of the alcoholic extract of Sphaeranthus indicus in streptozotocin-nicotinamide diabetic rats. 1854 78

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.
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PMID:Relationship between plasma leptin and plasma insulin levels in type-2 diabetic patients before and after treatment with glibenclamide and glimepiride. 1883 51

Permanent neonatal diabetes mellitus (PND), defined as diabetes diagnosed in the first 6 months of age and requiring life-long insulin therapy, is a rare disorder of unknown etiology. Activating mutations of the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-dependent potassium channel in beta-cells, have been found to cause 30-58% of cases of PND. Sulfonylurea treatment in theses patients reduces or eliminates the need for exogenous insulin. We report two Taiwanese boys who were diagnosed with PND at 1 and 4.5 months of age. They had been treated with exogenous insulin for 6 and 15 years, respectively. In September 2006, they were both found to have a KCNJ11 mutation (valine-to-methionine at codon 59; V59M). Glibenclamide successfully increased the basal C-peptide level, lowered HbA(1c), and reduced blood sugar excursions. In one patient, the insulin dose was reduced to 0.2 U/kg/day, and the other was able to discontinue insulin altogether. These two cases from Taiwan add to the experience with similar mutations reported in Caucasians.
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PMID:Improved diabetic control during oral sulfonylurea treatment in two children with permanent neonatal diabetes mellitus. 1977 48

Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. Several studies also suggest a pivotal role for K(ATP) channels in the seizure modulation. The aim of the present study was to evaluate the seizure threshold induced by pentylenetetrazole in diabetic mice at different times (3 days, 1-8 weeks) after induction of diabetes with streptozocin and to examine the possible role of ATP-sensitive potassium (K(ATP)) channels in this manner. Our data showed a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after streptozocin injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The K(ATP) channel opener cromakalim (0.1-30microg/kg, i.p.) significantly increased the seizure threshold in control mice. Although the K(ATP) channel blocker glibenclamide (0.5, 1mg/kg) had no effect, it prevented the effects of the potent dose of cromakalim (30microg/kg) on seizure threshold in control mice. Glibenclamide (1mg/kg, i.p.) also decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with cromakalim (10microg/kg, i.p.). Cromakalim (10microg/kg, i.p.) significantly increased the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide (1mg/kg, i.p.). We demonstrated a time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. This phenomenon might be due to the probable alteration in the K(ATP) channel functioning during the diabetic condition.
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PMID:ATP-sensitive potassium channels contribute to the time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. 2000 96


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