Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTIDIABETICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources

Chemometric insights into Lactiplantibacillus plantarum effects on onion (Allium cepa L.) metabolism and antidiabetic activity under cadmium stress.

Cadmium (Cd) is a toxic heavy metal that causes severe physiological damage in plants, inhibiting growth and ultimately reducing crop yield. Lactic acid bacteria regulate Cd availability through bioaccumulation and biosorption. This study evaluated the Cd tolerance of Lactiplantibacillus plantarum 10CH by determining its survival capacity under Cd stress and its potential to mitigate Cd-induced stress in onion (Allium cepa L.). The bacterial strain tolerated Cd concentrations up to 100 µM, and whole-genome sequencing identified genes involved in Cd biosorption, accumulation, and efflux. Exposure of onion to increasing CdCl2 concentrations significantly reduced root and shoot biomass. Inoculation with Lb. plantarum 10CH alleviated Cd stress at 100 µM, enhancing root and shoot biomass, reducing Cd accumulation, lowering oxidative damage markers, and stimulating antioxidant enzyme activities. Metabolic profiling revealed that Cd stress significantly reduced primary metabolites and amino acids, particularly at 100 µM, while bacterial inoculation restored key amino acids and peptides, including arginine, tyrosine, and glutamic acid. Chemometric analysis using unsupervised (PCA) and supervised (OPLS-DA) models revealed clear metabolite variation among untreated, Cd-stressed, and bacterial inoculated Cd-stressed onion leaves. Furthermore, leaf extracts exhibited α-glucosidase inhibitory activity, with the highest activity in control plants (IC50 = 425.2 ± 0.5 µg/mL). Cd-stressed plants showed moderate antidiabetic activity, which was significantly reduced by bacterial inoculation. Overall, these findings demonstrate that Lb. plantarum 10CH can survive under Cd stress and alleviates Cd-induced stress in onion, highlighting its potential as a bioinoculant to mitigate heavy metal stress.

Onions↗

Predictors of persistence of use of the novel antidiabetic agent acarbose.

BACKGROUND: A carbose is the first of a new class of antidiabetic agents, the alpha-glucosidase inhibitors. This study characterizes and identifies predictors of persistence of use of acarbose. METHODS: Medical, pharmaceutical, and demographic records were extracted for 2 cohorts of patients (social assistance recipients and seniors) from the databases of Quebec's provincial health plan. Patients were eligible for inclusion if they had received their first dispensation of acarbose between August 1, 1996, and December 31, 1997. The observation period included at least 1 year before the first dispensation and a minimum of 4 months after. RESULTS: New users of acarbose included 216 social assistance recipients and 677 seniors who were followed up for 82 914 and 270 041 person-days, respectively. Median persistence with acarbose treatment was 83 days (95% confidence interval, 75-105 days) for social assistance recipients and 105 days (95% confidence interval, 90-119 days) for seniors. In both cohorts, treatment by an endocrinologist vs another physician predicted longer treatment persistence. In the seniors cohort, additional determinants of (earlier) treatment discontinuation included a higher initial daily dose, previous treatment with insulin, and consultation with a gastroenterologist after treatment initiation. CONCLUSIONS: New users of acarbose showed low persistence in 2 cohorts of beneficiaries of Quebec's provincial health plan. Prescribing specialist was an important predictor of persistence in seniors and the socially assisted. The importance of 4 additional factors in seniors only led to hypotheses concerning population differences in treatment expectations and in the occurrence and tolerance of adverse effects.

Acarbose↗

Pharmacokinetic stereoselectivity of troglitazone, an antidiabetic agent, in the KK mouse.

Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two asymmetric centres. In the present study, the stereoselectivity of in vitro epimerization in plasma and organ homogenate and in vivo plasma disposition in the KK mouse, an animal model of non-insulin-dependent diabetes, was examined. In the incubation experiments at 37 degrees C, there was a fivefold to eightfold acceleration of epimerization at the 5 position of the thiazolidine ring in KK mouse plasma compared with that in buffer. However, no inversion at the 2 position of the chroman ring was observed. In addition, there was an approximately 1.3-fold difference in the epimerization rates among stereoisomers at the 2 position of the chroman ring. However, there were no differences in the values of the equilibrium constants of epimerization, and the ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring was almost unity. The acceleration of epimerization is thought to be due to the high degree of protein binding because of the relationship between the initial epimerization rate and the dilution ratio of the plasma. Although acceleration of epimerization was also observed in the 20% homogenates of liver, kidney, and intestine of the KK mouse, the degree of stereoselectivity was lower than in plasma. The analysis of the plasma disposition after intravenous administration of troglitazone stereoisomers, using a kinetic model, indicated that the metabolic clearance in the liver showed a 2.5-fold maximum difference among stereoisomers and that the stereoselectivity of epimerization was low.

Animals↗

The effect of the fat content of food on the pharmacokinetics and pharmacodynamics of SDZ FOX 988, an antidiabetic agent, in the dog.

SDZ FOX 988 (FOX 988) is being developed for the treatment of type II diabetes. The objective of this study was to examine the effect of the fat content of food on the pharmacokinetics and pharmacodynamics of FOX 988 following oral administration in the dog. In a randomized, cross-over design, four dogs received a single 10 mg kg-1 dose of 14C-FOX 988 suspension concomitantly with food containing 10% fat or 40% fat, or with the 10% fat food at 4 h post-dose. Serial blood, urine, and fecal samples were collected for 96 h and analyzed for total radioactivity. Blood concentrations of 53-450, the active metabolite of FOX 988, were also determined. Serum concentrations of beta-hydroxybutyrate and glucose, pharmacological markers for the antidiabetic effects, were measured serially for 24 h after dosing. The animals receiving the low-fat meal at dosing and at 4 h post-dose exhibited similar extents of absorption, as shown by similar AUC values and urinary radioactivity recovery. Administration of the high-fat meal at dosing significantly enhanced the absorption of FOX 988 and resulted in high blood concentrations of 53-450. However, no significant differences in the pharmacological activity of the drug were observed among the three treatments.

3-Hydroxybutyric Acid↗

The effect of food on the absorption of 14C-SDZ FOX 988, an antidiabetic agent, in healthy human volunteers.

The objective of this study is to examine the effect of food on oral absorption of SDZ FOX 988 (FOX 988), an antidiabetic agent, and circulating levels of its active metabolite, SDZ 53-450 (53-450). Sixteen normal volunteers received a single 10 mg dose of 14C-FOX 988, either as gelatin capsules or in a suspension (0.5% CMC). For subjects receiving each formulation, four subjects received a meal, consisting of 50% fat by calories, immediately following dosing, while the other four received the same meal at 2 h post-dose. Serial blood, urine, and fecal samples were collected for 120 h and analyzed for total radioactivity. Blood concentrations of 53-450 were analyzed using an HPLC-UV method. Concomitant administration with food increased the extent of FOX 988 absorption from either suspension or capsule, as shown by an increase in AUC and in urinary recovery of radioactivity. Blood concentrations of 53-450 were only detected in subjects receiving food at dosing. No difference in absorption was observed between the capsule and the suspension. Results from this study showed that oral absorption of FOX 988 is enhanced by co-administration of food in normal volunteers.

Absorption↗

The antidiabetic agent, gliclazide, reduces high insulin-enhanced neutrophil-transendothelial migration through direct effects on the endothelium.

BACKGROUND AND AIM: Many lines of evidence indicate that hyperinsulinemia might be associated with coronary atherosclerosis, and, currently, there are no effective strategies for preventing this. We previously reported that high insulin enhances neutrophil-transendothelial migration, a process that involves increased surface presentation of platelet endothelial cell adhesion molecule-1 (PECAM-1) through a mitogen-activated protein (MAP) kinase-dependent event. In this current study, we examined if antidiabetic agents, especially K(ATP) channel blockers, might similarly protect against the leukocyte-endothelial cell interactions enhanced by high insulin. METHODS: Neutrophils transmigration across umbilical vein endothelial cells (in high insulin medium) with or without K(ATP) channel blockers was performed. Neutrophil migration was quantified by measuring myeloperoxidase, and surface expression of endothelial PECAM-1 was examined using cell-surface enzyme immunoassay. RESULTS: Neutrophil-transendothelial migration and PECAM-1 expression were enhanced by insulin (100 micro U/mL, 24 h) and were attenuated by gliclazide (20 micro M), but not by other K(ATP) channel blockers (glibenclamide, nateglinide, and glimepiride). Neutrophil migration and PECAM-1 expression were also increased by the mitogen-activated protein (MAP) kinase activator, anisomycin (1 micro M), and also attenuated by gliclazide. Nitric oxide (NO) synthase inhibitors did not modify either gliclazide effect. CONCLUSIONS: Our results suggest that the K(ATP) channel blocker, gliclazide, blocks high insulin-mediated neutrophil migration and PECAM-1 expression. These gliclazide effects may be mediated through the inhibition of MAP kinase activation and are unrelated to NO production.

Anisomycin↗

Effect of vitamin E and C supplementation combined with oral antidiabetic therapy on the endothelial dysfunction in the neonatally streptozotocin injected diabetic rat.

BACKGROUND: This study investigates the contribution of vitamin supplementation to the efficacy of oral antidiabetic therapy on the reversal of endothelial dysfunction in a model of type-2 diabetes in rat. METHODS: Diabetes was induced by streptozotocin injection to neonatal rats which were breastfed for 4 weeks, then fed 6 weeks with normal food or food supplemented with 2% vitamin E and 4% vitamin C. Some diabetic rats were treated with gliclazide for 6 weeks. Endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside (SNP) were recorded in thoracic aortic rings. Plasma insulin, HbA(1c) and antioxidant vitamins (A, C and E); plasma and aortic malondialdehyde (MDA) levels were determined. RESULTS: Induction of diabetes resulted in decreased body weight and increased blood glucose, plasma insulin and HbA(1c) levels compared to controls. Acetylcholine relaxation was impaired in diabetic aorta, while SNP relaxation remained unchanged. Aortic MDA level was significantly higher, while plasma vitamin levels were lower in diabetic rats. Diminished acetylcholine response, enhanced aortic MDA level and decreased plasma vitamin levels were all restored after gliclazide and/or vitamin therapy. However, vitamin supplementation in control rats significantly impaired acetylcholine relaxations and increased aortic MDA levels. CONCLUSIONS: Apparently, a selective endothelial dysfunction accompanies the imbalance in oxidant/antioxidant status in the type-2 diabetes model of rat and gliclazide and/or vitamin supplementation improves the impairment in diabetic vasculature. However, vitamin supplementation triggers oxidative stress in normal aortic tissue, thereby, leads to endothelial dysfunction; indicating that nutritional extra-supplementation of antioxidant vitamins isn't advisable for normal subjects, although it's beneficial in disease status.

Acetylcholine↗

Genotoxicity in rats treated with the antidiabetic agent, rosiglitazone.

Rosiglitazone (RSG), a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by increasing insulin sensitivity. The therapeutic mode of action of RSG involves its activity as a highly selective and potent agonist for peroxisome proliferator-activated receptor-gamma. Although other drugs in this class have displayed unacceptable hepatotoxicity, RSG was approved for human use. The package insert indicates that RSG has minimal genotoxicity, but information on the genotoxicity of RSG is not available in the published literature. In this study, we used the single cell gel electrophoresis (SCGE)/Comet assay to investigate the DNA damage in peripheral blood and liver cells of rats treated with RSG. Sixteen male Sprague-Dawley rats were randomly distributed into four groups, and dosed daily by oral gavage with 0.0, 0.5, 1.0, and 2.0 mg/kg/day RSG. The rats dosed with 2.0 mg/kg/day RSG received an approximately 10-times the area under the curve concentration of the maximum recommended human daily dose. After 14 days of treatment, the rats were euthanized, and peripheral blood and liver were collected and processed for the Comet assay. A dose-dependent increase in DNA damage (as assessed by % tail DNA and Olive Tail Moment) was observed in the hepatocytes of RSG-treated groups, with significant increases detected between rats treated with all the doses of RSG and the control, and between rats treated with different RSG doses (P < 0.05 - P < 0.0001). In contrast, DNA damage was detected in peripheral blood lymphocytes only in rats treated with the higher RSG doses (1.0 and 2 mg/kg/day). Taken together, the data indicate that RSG is able to induce primary DNA damage in rats, with greater damage being detected in liver cells than lymphocytes.

Animals↗

AO-128, alpha-glucosidase inhibitor: antiobesity and antidiabetic actions in genetically obese-diabetic rats, Wistar fatty.

Antiobesity and antidiabetic actions of the alpha-glucosidase inhibitor AO-128 were examined using genetically obese-diabetic rats, Wistar fatty. Ten-week-old, male fatty rats were kept on CE-2 diet containing 10 or 25 ppm of AO-128 for 4 weeks. The average drug intake was calculated to be 0.74 or 1.78 mg/kg/day from the average food intake, respectively. The intestinal maltase and sucrase activities were decreased by AO-128 in a dose-related fashion. Food intake of fatty rats treated with AO-128 was decreased throughout the experiment. This decrease in food intake could hardly be explained only by diarrhea which occurred for the first 5 days of the administration of AO-128. AO-128 normalized hyperglycemia and markedly reduced hypertriglyceridemia and hyperinsulinemia in fatty rats. In addition, AO-128 decreased body weight gain, food efficiency, epididymal adipose tissue weight, carcass weight, and body fat deposition. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.

Animals↗

Effect of physiological concentrations of insulin and antidiabetic drugs on RNA release from isolated liver nuclei.

The addition of 10(-11) M insulin to a cell-free system from rat liver promotes the release of messengerlike RNA from isolated prelabeled nuclei. The stimulation was similar whether the nuclei were preincubated with insulin, or if insulin was added directly to the cell-free system with or without a protease inhibitor. Dot blot hybridization using cloned cDNA for alpha 2u-globulin mRNA showed that this was one of the messages whose release was enhanced by insulin. Nuclei isolated from rats treated with either of the antidiabetics tolbutamide or tolazamide showed no increase in RNA release in the presence of insulin over the concentration range 10(-5) - 10(-14) M. Furthermore, these nuclei did not release detectable levels of alpha 2u-globulin mRNA.

Animals↗

Antidiabetic AD4743 enhances adipocyte differentiation of 3T3 T mesenchymal stem cells.

AD4743 is an antidiabetic agent that, when added to fetal bovine serum (FBS), has been shown to have adipogenic activity for some proadipocyte cell lines once they reach confluence. In the current study, the effects of AD4743 on the growth and adipocytic differentiation of 3T3 T multipotential mesenchymal stem cells have been tested. 3T3 T cells, unlike other cells capable of undergoing adipocyte differentiation, are routinely induced to differentiate at low cell density. This is done using platelet-poor human plasma (HP), a potent inducer of growth arrest and differentiation. AD4743 (0-200 micrograms/ml) was tested in varied concentrations of HP or FBS, at varied cell densities, and at various times during growth and differentiation. AD4743 slowed the growth rate of 3T3 T cells and it induced their differentiation in a dose-dependent manner in medium containing 10% FBS once they reached confluence. The data suggest that the ability of AD4743 to inhibit growth may also be coupled with its ability to enhance differentiation. In addition, AD4743 (1-10 micrograms/ml) in the presence of 25% HP markedly increased the kinetics of adipocyte differentiation, at low (less than 5,000 cells/cm2) or high cell density. Greater than 50% cell differentiation could be achieved in 2 days in low density cultures; 80-95% differentiation could be achieved in just 4 days, compared to 8-12 days in a typical culture. The maximum amount of differentiation in HP was potentiated by AD4743 to a greater degree in poor lots of HP; however, the kinetics were increased in all lots. Adipocytic differentiation was measured both morphologically and by Northern blot analyses of differentiation-specific genes. AD4743 at 1-10 micrograms/ml appeared to be most effective, depending on the cell density and other conditions. The mechanism of action of AD4743 remains to be elucidated, but the enhancement of adipocyte differentiation does not appear to occur via an insulin-dependent pathway.

Adipose Tissue↗

The interaction of human serum albumin with a novel antidiabetic agent--SU-118.

SU-118 is a newly synthesized antidiabetic agent and shows the best hypoglycemic effect among a series of analogs. Its binding properties and binding sites located on human serum albumin (HSA) have been studied using UV absorption and fluorescence spectroscopy. The results of spectroscopic study and the thermodynamic parameters obtained suggest that SU-118 binds to the hydrophobic cavity of human serum albumin and the hydrophobic interaction is the predominant intermolecular force stabilizing the complex. Fluorescent probe displacement studies show that SU-118 can displace competitively both dansylamide and dansylsarcosine from HSA. It is suggested that SU-118 can bind to both site I and site II, but the primary interaction may take place at site I. A binding constant of 1.4 x 10(4) M(-1) and a binding site of 2.0 are obtained from absorbance titration data. The value of binding constant is of the same order of magnitude as that from fluorescence titration. This study provides a molecular basis for elucidating the mechanism of drug acting and predicting unfavorable drug interaction.

Binding Sites↗

Preparation and antidiabetic activity of cyclic sulfonylthiourea derivatives.

3-Substituted 5-methyl-1-(p-[(3,5-dimethyl)pyrazol-1-yl]-, 5-methyl-1-(p-[(5-methyl-3-carboxy)pyrazol-1-yl]-, 1-(p-[(3-methyl-5-phenyl)pyrazol-1-yl]-, and 1-(p-[(3-methyl-4-bromo-5-phenyl)pyrazol-1-yl]benzenesulfonyl)-2-thiohydantoin and their 5-methyl-2-thiohydantoin and 5,6-dihydro-4(3H)-oxo-2(1H)-pyrimidinethione derivatives were prepared for evaluation as hypoglycemic agents. Biological testing showed that some of these compounds possessed antidiabetic activity.

Animals↗

Antidiabetic behavior of biguanides.

The existence of active electron pairs on some nitrogen atoms in phenformin hydrochloride is inferred from the presence of a hydrogen catalytic polarographic wave. This finding emphasizes the ability of biguanides to form hydrogen bridges with other molecular species such as amino acids and proteins, as well as to form coordination complexes with zinc and other metallic cations by means of these electron pairs. The antidiabetic action of phenformin and other related biguanides can be explained in terms of competition between these molecules and insulin to coordinate cationic oligoelements together with their ability to form hydrogen bonds between the biguanide moiety and insulin itself.

Biguanides↗

Prevention of diet-induced type 2 diabetes in the C57BL/6J mouse model by an antidiabetic herbal formula.

Significant positive effects of an antidiabetes herbal formula (ADHF) on the prevention of progressive diet-induced type 2 diabetes (NIDDM) in the well recognized C57BL/6J mouse model were demonstrated. The results of the present studies confirm that C57BL/6J mice, through a genetic predisposition, developed NIDDM-like symptoms on a regular schedule when fed solely on a diabetes induction diet containing high fat, high simple carbohydrate and low fibre. Blood glucose levels consistent with type 2 diabetes were detected after 8 weeks on this induction diet. In contrast, no members of the prevention study groups of C57BL/6J mice, which had ADHF mixed into their diabetes induction diet, developed progressive evidence of NIDDM-like symptoms. Specific parameters observed to be significantly reduced in mice in the prevention diet groups fed ADHF mixed into the diabetes induction diet compared with the diabetes positive control groups fed diabetes induction diet only were clinical signs, blood glucose and serum insulin levels, insulin resistance and histopathological changes in major organs. This is the first report to our knowledge to show in vivo evidence for the successful prevention of progressive NIDDM-like symptoms by the addition of an anti-diabetes herbal formula to a effective diabetes induction diet.

Animals↗

Analgesic, antiinflammatory and antidiabetic properties of Harpagophytum procumbens DC (Pedaliaceae) secondary root aqueous extract.

South Africa is blessed with a rich floral biodiversity of medicinally useful plants. One such plant is Harpagophytum procumbens DC (Family: Pedaliaceae). H. procumbens is widely used in South African traditional medicine for the treatment, management and/or control of a variety of human ailments. In the present study, the analgesic effect of H. procumbens secondary root aqueous extract was evaluated in mice, using the 'hot-plate' and 'acetic acid' test methods; while the antiinflammatory and antidiabetic effects of the plant's secondary root extract were investigated in rats. Fresh egg albumin-induced pedal oedema and streptozotocin (STZ)-induced diabetes mellitus were used as experimental test models of inflammation and diabetes Diclofenac (DIC, 100 mg/kg i.p.) was used as a reference analgesic and antiinflammatory agent for comparison. Chlorpropamide (250 mg/kg p.o.) was used as a reference hypoglycaemic agent for comparison. H. procumbens root aqueous extract (HPE, 50-800 mg/kg i.p.) produced significant (p < 0.05-0.001) analgesic effects against thermally and chemically induced nociceptive pain stimuli in mice. H. procumbens root extract (HPE, 50-800 mg/kg i.p.) also produced dose-related, significant reductions (p < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw oedema. Furthermore, the plant extract (HPE, 50-800 mg/kg i.p.) produced dose-dependent, significant reductions (p < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. The results of this experimental animal study indicate that H. procumbens root aqueous extract possesses analgesic, antiinflammatory and hypoglycaemic properties, and lend pharmacological support to the suggested folklore uses of Harpagophytum procumbens root in the management and/or control of painful, arthritic and other inflammatory conditions, as well as for adult-onset, type-2 diabetes mellitus in some communities of South Africa.

Acetic Acid↗

Antidiabetic effect of Cinnamomum cassia and Cinnamomum zeylanicum in vivo and in vitro.

Rats were given Cinnamomum cassia bark or extracts from Cinnamomum cassia and zeylanicum to evaluate blood glucose and plasma insulin levels in rats under various conditions. The cassia extract was superior to the zeylanicum extract. The cassia extract was slightly more efficacious than the equivalent amount of Cassia bark. A decrease in blood glucose levels was observed in a glucose tolerance test (GTT), whereas it was not obvious in rats that were not challenged by a glucose load. The elevation in plasma insulin was direct since a stimulatory in vitro effect of insulin release from INS-1 cells (an insulin secreting cell line) was observed. Thus the cassia extract has a direct antidiabetic potency.

Animals↗

Evaluation of the antidiabetic action of Mangifera indica in mice.

The leaves of Mangifera indica were assessed for antidiabetic properties using normoglycaemic, glucose-induced hyperglycaemia and streptozotocin (STZ) induced diabetic mice. The aqueous extract produced a reduction of blood glucose level in normoglycaemic and glucose-induced hyperglycaemia, but did not have any effect on streptozotocin-induced diabetic mice. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity.

Animals↗