Influence of experimental diabetes and insulin treatment on the enantioselective pharmacokinetics of mexiletine and its metabolites

2014 ◽  
Vol 92 (3) ◽  
pp. 263-266
Author(s):  
Ana Leonor Pardo Campos Godoy ◽  
Edson Z. Martinez ◽  
Maria Paula Marques ◽  
Andréia de Carvalho Leone ◽  
Eduardo Barbosa Coelho ◽  
...  
Keyword(s):  
Body Mass ◽  
Insulin Treatment ◽  
Experimental Diabetes ◽  
Area Under The Curve ◽  
Diabetic Rats ◽  
Control Group ◽  
Blood Collection ◽  
Glucose Levels ◽  
Streptozotocin Induced Diabetes ◽  
Enantioselective Pharmacokinetics

This study evaluates the influence of streptozotocin-induced diabetes on the kinetic disposition and metabolism of mexiletine (MEX) enantiomers in rats. Animals in the control (n = 6 for each blood collection time), diabetic (single intravenous dosage of 45 mg·(kg body mass)−1 of streptozotocin), and insulin-treated groups (diabetic rats treated daily with 2 IU insulin) received by gavage a single dose of 10 mg·(kg body mass)−1 racemic MEX. MEX enantiomers and the metabolites hydroxymethylmexiletine (HMM) and p-hydroxymexiletine PHM) were analyzed by LC-MS/MS. Statistical analysis was based on a serial sacrifice design, and parameter estimation was performed using a Bayesian modeling procedure. Area under the curve (AUC) for the (−)-(R) enantiomers of MEX, HMM, and PHM did not differ between the control and diabetic groups. However, AUC for (+)-(S)-MEX and (+)-(S)-HMM were lower in the diabetic than in the control group. Insulin treatment recovered glucose levels to normal and the (+)-(S)-MEX AUC and (+)-(S)-HMM AUC became similar to the AUCs observed in the nondiabetic animals.

Reversibility of renal tubular dysfunction in streptozotocin-induced diabetes in the rat

1992 ◽  
Vol 70 (7) ◽  
pp. 977-982 ◽  
Author(s):  
S. Chouinard ◽  
C. Viau
Keyword(s):  
Molecular Weight ◽  
Urinary Excretion ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
Control Group ◽  
Low Molecular Weight ◽  
Tubular Dysfunction ◽  
Alanine Aminopeptidase ◽  
Group A ◽  
Streptozotocin Induced Diabetes

Enzymuria and specific proteinuria were examined over a period of 19 days in 4 groups of 5 rats: a control group, a non-diabetic polyuric group, a group of streptozotocin-induced diabetic rats treated with insulin as of the 10th day after the injection of the drug, and a similar group of untreated diabetic rats. Increased urinary excretion of β-N-acetyl-D-glucosaminidase, lactate dehydrogenase, and alanine aminopeptidase was observed shortly after the induction of diabetes. It was partly or totally reversible following insulin treatment. Nondiabetic polyuria had a slight effect on the excretion of alanine aminopeptidase only. The urinary excretion of β2-microglobulin also rapidly increased after the onset of diabetes to a level approximately 50 times the control values. This effect was largely reversible with insulin treatment and was absent in the nondiabetic polyuric group. A small but significant 3-fold increase in albumin excretion was also noted but was not affected by insulin treatment. We conclude that streptozotocin-induced diabetes causes an early tubular dysfunction that is unrelated to polyuria and is reversible upon insulin treatment. This tubular dysfunction is best revealed by the urinary excretion of the low molecular weight protein β2-microglobulin. Our results suggest that it would be of interest to further examine the usefulness of sensitive markers of tubular dysfunction, especially low molecular weight proteinuria, in the detection of early stages of diabetic nephropathy.Key words: diabetic nephropathy, enzyme, urine, proteinuria, β2-microglobulin, streptozotocin, insulin, rat.

scholarly journals Hypoglycemic Potential of Dietary Supplementation of Protein Isolate from Fermented Cucumeropsis manii in Streptozotocin Induced Hyperglycemic in Male Wistar Albino Rats

2021 ◽  
pp. 31-42
Author(s):  
A. O. Abiola ◽  
A. O. Iyoribhe ◽  
S. A. Adeniyi ◽  
O. B. Adu ◽  
A. S. Ogunbowale ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Concentration ◽  
Diabetic Control ◽  
Protein Isolate ◽  
Diabetic Rats ◽  
Control Group ◽  
Albino Rats ◽  
Antioxidant Enzyme Activities ◽  
Cvd Risk ◽  
Streptozotocin Induced Diabetes

The effect of Protein isolate from fermented melon seeds (Ogiri Protei Isolates; OPI) of Cucumeropsis manii on blood glucose, lipid profile, and antioxidant enzyme activities in streptozotocin (STZ)-induced diabetic rats was investigated. Thirty Male Wistar rats were divided into five equal groups. GThe first control group with no exposure. The second group of rats with Streptozotocin-induced non-treated diabetes. The 3rd and 4th groups of rats with Streptozotocin-induced diabetes supplemented with Ogiri protein isolates (200, 600 mg/kg in diet). And the 5th group of rats with Streptozotocin-induced diabetes administered glibenclamide in a dose 500 ug/kg in diet [17]. The OPI was administered for 6 weeks. The administration of OPI reduced the blood glucose concentration of the STZ-induced diabetic rats. Sera and hepatic superoxide dismutase, activities of the STZ-induced diabetic rats were significantly (P< 0.05) increased in comparison with the diabetic control rats. Lipid peroxidation of the supplemented OPI diabetic rats was significantly (P< 0.05) decreased in comparison with the diabetic control rats as the administration of OPI to the STZ-induced diabetic rats significantly increased the enzymes’ activities. The concentration of low-density lipoproteins in the OPI supplemented rats was significantly elevated. These data demonstrate that OPI supplements might be beneficial for correcting hyperglycemia but the consumption of OPI can modulate some tissue lipids in a direction not beneficial for CVD risk in patients with diabetes.

scholarly journals BLOOD GLUCOSE LEVELS AND THE MICROSCOPIC STRUCTURE OF KIDNEY WISTAR RAT DIABETES MELLITUS UNDER THE EFFECT OF LAWSONIA INERMIS (LINN.) LEAVES ETHANOLIC EXTRACT

2018 ◽  
Vol 11 (4) ◽  
pp. 257
Author(s):  
Mutiara Indah Sari ◽  
Maya Anjelir Antika ◽  
Dwi Rita Anggraini
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Ethanolic Extract ◽  
Wistar Rat ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Control Group ◽  
Lawsonia Inermis ◽  
Control Group Design ◽  
Glucose Levels

 Objective: Lawsonia inermis (Linn.) leaves are one of the alternative medicines to treat diabetes mellitus in Indonesia. We investigated the blood glucose level (BGL) of the L. inermis (Linn.) leaves ethanolic extract (LLEE) leaves and evaluated the histopathological alterations in diabetic rats.Methods: This study was an experimental study with posttest - only control group design. Alloxan (120 mg/kg, intraperitoneally)-induced diabetic rats. 35 of Wistar rats (Rattus norvegicus) were divided randomly into five groups, i.e. K: Normal control, P1: Diabetic control, and P2, P3, and P4 (200 mg/kg body weight [BW], 400 mg/kg BW, and 600 mg/kg BW of LLEE, orally) for 28 days. At the end of the treatment, the rats were sacrificed to obtain the kidney for histopathological evaluation using hematoxylin and eosin technique. BGLs were conducted using a glucose meter (GlucoDR).Results: One-way ANOVA test showed that dose 400 mg/kg BW of the LLEE was related to BGL of alloxan-induced diabetic rats (p=0.000). The histopathological of kidney showed glomerular inflammation (GI), epithelial membrane lining degeneration, vascular congestion, and interstitial tubule hemorrhage at diabetic control (P1). Meanwhile, treated with 600 mg/kg BW of LLEE (P4) showed increase cellular regeneration as normal architecture of the kidney.Conclusion: The LLEE at dose 400 mg/kg BW effective decreased BGL and was able to restore the kidney destruction of alloxan-induced diabetic rats at dose 600 mg/kg BW.

scholarly journals EVALUATION OF ANTIDIABETIC AND ANTIOXIDANT EFFECTS OF ETHANOLIC LEAF EXTRACT OF ERYTHRINA ABBYSINICA LAM, EX DC

2018 ◽  
Vol 11 (8) ◽  
pp. 300
Author(s):  
Kamadyaapa Davie Rexon ◽  
Gondwe Mavuto Masopera ◽  
Shauli Mathulo ◽  
Sewani Rusike Constance ◽  
Nkeh Chungag Benedicta
Keyword(s):  
Blood Glucose ◽  
Leaf Extract ◽  
Antioxidant Properties ◽  
Diabetic Rats ◽  
Control Group ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Ethanolic Leaf Extract ◽  
Antioxidant Effects

  Objective: This study was conducted to scientifically evaluate the antidiabetic and antioxidant effects of ethanolic leaf extract of Erythrina abbysinica (EEA).Methods: Acute and sub-chronic effects of EEA at 100, 200, and 400 mg/kg/bwt and glibenclamide (GL) at 5 mg/kg/bwt. were evaluated in both normal and streptozotocin (STZ)-induced diabetic male Wistar rats (250–300 g). The acute studies were performed using oral glucose tolerance test (OGTT). In sub-chronic studies, animals were orally administered with EEA and GL daily for 6 w. Brine shrimp assay was used to determine the toxicity of EEA. 1, 1-diphenyl-2-picrylhydrazyl, ferric reducing capacity of plasma, and thiobarbituric acid reactive substances assays were used to determine antioxidant properties of EEA.Results: Following OGTT, EEA significantly (p<0.05) and dose-dependently (100, 200, and 400 mg/kg/bwt) decreased blood glucose levels in both normal and STZ-induced diabetic rats when compared with positive and negative control counterparts at all-time points, whereas GL significantly (p<0.05) decreased blood glucose only in normal rats but not in diabetic rats. Daily, oral administration of EEA for 6 w significantly (p<0.05) and dose-dependently (100, 200, and 400 mg/kg/bwt) decreased blood glucose levels in STZ-induced diabetic rats when compared with the diabetic control group. EEA revealed weak toxicity with a lethal concentration50 value of 997 μg/ml). Furthermore, EEA showed significant free radical scavenging, total antioxidant, and anti-lipid peroxidative capacities.Conclusion: The study has shed more light on the scientific basis for the use of E. abbysinica in management of diabetes in some communities of Eastern Cape of South Africa.

scholarly journals Comparison of Glucose Influx and Blood Flow in Retina and Brain of Diabetic Rats

2004 ◽  
Vol 24 (4) ◽  
pp. 449-457 ◽  
Author(s):  
Michelle A. Puchowicz ◽  
Kui Xu ◽  
Danielle Magness ◽  
Casey Miller ◽  
W. David Lust ◽  
...  
Keyword(s):  
Blood Flow ◽  
Glucose Transporter ◽  
Dry Weight ◽  
Diabetic Rats ◽  
Indicator Method ◽  
Glucose Levels ◽  
Diabetic Retina ◽  
Nondiabetic Control ◽  
Microvascular Pathology ◽  
Streptozotocin Induced Diabetes

Diabetes is associated with extensive microvascular pathology and decreased expression of the glucose transporter (GLUT-1) in retina, but not brain. To explore the basis of these differences, the authors simultaneously measured glucose influx (μmol · g−1 · min−1) and blood flow (mL · g−1 · min−1) in retina and brain cortex of nondiabetic control rats (normoglycemic and acute-hyperglycemic) and in rats with streptozotocin-induced diabetes (with or without aminoguanidine (AMG) treatment) using a single-pass, dual-label indicator method. In addition, tissue glucose and adenosine triphosphate (nmol/mg dry weight) levels were measured. Glucose influx in retina exceeded that of cortex by about threefold for both the nondiabetic and diabetic groups. In contrast, blood flow in retina was significantly lower than in cortex by about threefold for each group. Retinal and cortical glucose influx in the diabetic rats was lower than in the nondiabetic acute-hyperglycemic group, but not in the normoglycemic group. Blood flow in these tissues remained relatively unchanged with glycemic conditions. The glucose levels in the diabetic retina (aminoguanidine untreated and aminoguanidine treated) were fourfold to sixfold greater than the nondiabetic retina. The cortical glucose levels remained unchanged in all groups. These data suggest that the accumulation of glucose in the diabetic retina cannot be explained by increased endothelial-glucose uptake or increased vascular membrane permeability.

Inhibitory Effect of Astraxanthin Combined with Flavangenol® on Oxidative Stress Biomarkers in Streptozotocin-Iduced Diabetic Rats

2008 ◽  
Vol 78 (45) ◽  
pp. 175-182 ◽  
Author(s):  
Masako Nakano ◽  
Natsumi Orimo ◽  
Nakako Katagiri ◽  
Masahito Tsubata ◽  
Jiro Takahashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxide ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Control Group ◽  
Cataract Formation ◽  
Oxidative Stress Biomarkers ◽  
Stress Biomarkers ◽  
Liver And Kidney ◽  
Streptozotocin Induced Diabetes

In this study, the effect of dietary antioxidants, such as astaxanthin and Flavangenol®, and a combination of both, in counteracting oxidative stress in streptozotocin-induced diabetes was investigated. Streptozotocin-induced diabetic rats were divided into four groups: control, astaxanthin, Flavangenol, and combined astaxanthin and Flavangenol (mix group). Each group other than the control group was fed with an astaxanthin diet (0.1 g/kg), Flavangenol diet (2.0 g/kg), or an astaxanthin (0.1 g/kg)-Flavangenol (2.0 g/kg) mixture diet, respectively. After 12 weeks of feeding, the results showed that the lipid peroxide levels of plasma and lens and the plasma triglyceride (TG) level in the mix group were significantly decreased by 44%, 20%, and 20%, respectively, compared with the control group. In the mix group, lipid peroxidation was also significantly reduced by 70% in the liver and 20% in the kidney compared with the control group. Furthermore, the level of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mix group was significantly lower, 36%, than the control group. The α-tocopherol concentrations in the plasma, liver, and kidney in the astaxanthin and mix groups were significantly higher, 3-9 times, than in the control group. The degree of cataract formation in the Flavangenol and mix groups tended to be lower than the control group. These results indicate that the combination of astaxanthin with Flvangenol has an improved protective effect on oxidative stress associated with streptozotocin-induced diabetes than either agent used alone. Thus, this combination may be beneficial in preventing the progression of diabetic complications.

scholarly journals Electroacupuncture-Induced Cholinergic Nerve Activation Enhances the Hypoglycemic Effect of Exogenous Insulin in a Rat Model of Streptozotocin-Induced Diabetes

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Yu-Chen Lee ◽  
Te-Mao Li ◽  
Chung-Yuh Tzeng ◽  
Yu-Wen Cheng ◽  
Ying-I Chen ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Challenge Test ◽  
Diabetic Rats ◽  
Hypoglycemic Effect ◽  
Control Group ◽  
Exogenous Insulin ◽  
Glucose Lowering ◽  
Cholinergic Nerve ◽  
Streptozotocin Induced Diabetes ◽  
The Relationship

The aim of this study is to explore the mechanisms by which electroacupuncture (EA) enhances the hypoglycemic effect of exogenous insulin in a streptozotocin- (STZ-) diabetic rats. Animals in the EA group were anesthetized and subjected to the insulin challenge test (ICT) and EA for 60 minutes. In the control group, rats were subjected to the same treatment with the exception of EA stimulation. Blood samples were drawn to measure changes in plasma glucose, free fatty acids (FFA), and insulin levels. Western blot was used to assay proteins involved in insulin signaling. Furthermore, atropine, hemicholinium-3 (HC-3), and Eserine were used to explore the relationship between EA and cholinergic nerve activation during ICT. EA augmented the blood glucose-lowering effects of EA by activating the cholinergic nerves in STZ rats that had been exposed to exogenous insulin. This phenomenon may be related to enhancement of insulin signaling rather than to changes in FFA concentration.

scholarly journals The effect of streptozotocin-induced diabetes and of insulin supplementation on glycogen metabolism in rat liver

1977 ◽  
Vol 168 (3) ◽  
pp. 541-548 ◽  
Author(s):  
R L Khandelwal ◽  
S M Zinman ◽  
E J Zebrowski
Keyword(s):  
Phosphatase Activity ◽  
Insulin Treatment ◽  
Glycogen Synthase ◽  
Glycogen Metabolism ◽  
Diabetic Rats ◽  
Phosphorylase Kinase ◽  
Metabolizing Enzymes ◽  
Heat Stable ◽  
Heat Stable Protein ◽  
Streptozotocin Induced Diabetes

The effects of streptozotocin-induced diabetes and of insulin supplementation to diabetic rats on glycogen-metabolizing enzymes in liver were determined. The results were compared with those from control animals. The activities of glycogenolytic enzymes, i.e. phosphorylase (both a and b), phosphorylase kinase and protein kinase (in the presence or in the absence of cyclic AMP), were significantly decreased in the diabetic animals. The enzyme activities were restored to control values by insulin therapy. Glycogen synthase (I-form) activity, similarly decreased in the diabetic animals, was also restored to control values after the administration of insulin. The increase in glycogen synthase(I-form) activity after insulin treatment was associated with a concomitant increase in phosphoprotein phosphatase activity. The increase in phosphatase activity was due to (i) a change in the activity of the enzyme itself and (ii) a decrease in a heat stable protein inhibitor of the phosphatase activity.

scholarly journals Antecedent glycemic control reduces severe hypoglycemia-induced neuronal damage in diabetic rats

2013 ◽  
Vol 304 (12) ◽  
pp. E1331-E1337 ◽  
Author(s):  
Candace M. Reno ◽  
Tariq Tanoli ◽  
Adam Bree ◽  
Dorit Daphna-Iken ◽  
Chen Cui ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Brain Damage ◽  
Insulin Treatment ◽  
Neuronal Damage ◽  
Blood Glucose Control ◽  
Severe Hypoglycemia ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Sprague Dawley Rats

Brain damage due to severe hypoglycemia occurs in insulin-treated people with diabetes. This study tests the hypothesis that chronic insulin therapy that normalizes elevated blood glucose in diabetic rats would be neuroprotective against brain damage induced by an acute episode of severe hypoglycemia. Male Sprague-Dawley rats were split into three groups: 1) control, non-diabetic; 2) STZ-diabetic; and 3) insulin-treated STZ-diabetic. After 3 wk of chronic treatment, unrestrained awake rats underwent acute hyperinsulinemic severe hypoglycemic (10–15 mg/dl) clamps for 1 h. Rats were subsequently analyzed for brain damage and cognitive function. Severe hypoglycemia induced 15-fold more neuronal damage in STZ-diabetic rats compared with nondiabetic rats. Chronic insulin treatment of diabetic rats, which nearly normalized glucose levels, markedly reduced neuronal damage induced by severe hypoglycemia. Fortunately, no cognitive defects associated with the hypoglycemia-induced brain damage were observed in any group. In conclusion, antecedent blood glucose control represents a major modifiable therapeutic intervention that can afford diabetic subjects neuroprotection against severe hypoglycemia-induced brain damage.

Change in tissue concentrations of lipid hydroperoxides, vitamin C and vitamin E in rats with streptozotocin-induced diabetes

1999 ◽  
Vol 96 (2) ◽  
pp. 185-190 ◽  
Author(s):  
Fang SUN ◽  
Kozue IWAGUCHI ◽  
Reiko SHUDO ◽  
Yoshie NAGAKI ◽  
Kyoko TANAKA ◽  
...  
Keyword(s):  
Vitamin E ◽  
Vitamin C ◽  
Tissue Concentration ◽  
Diabetic Rats ◽  
Control Group ◽  
Specific Method ◽  
Lipid Hydroperoxides ◽  
Tissue Concentrations ◽  
Streptozotocin Induced Diabetes ◽  
The Brain

The tissue concentration of lipid hydroperoxides, which was determined by a specific method involving chemical derivatization and HPLC, increased significantly in the heart, liver, kidney and muscle of diabetic rats 8 weeks after the intraperitoneal injection of streptozotocin compared with that of the control group. These results demonstrate that an enhanced oxidative stress is caused in these tissues by diabetes. Vitamin C concentrations of the brain, heart, lung, liver, kidney and plasma of the diabetic rats decreased significantly after 8 weeks compared with those of the control group. Vitamin E concentrations of the brain, heart, liver, kidney, muscle and plasma of the diabetic rats increased significantly after 4 weeks compared with the control group. After 8 weeks, an elevation in vitamin E concentration was observed in the heart, liver, muscle and plasma of the diabetic rats.

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