Interaction between diazepam and oral antidiabetic agents on serum glucose, insulin and chromium levels in rats

Alahmed, FawzeyaA; El-Denshary, Ezz-El-Din S.; Zaki, M. J.; El-Sawaf, H. A.; Abu-Jayyab, Abdulrahim

doi:10.1007/bf01114687

Cited by 7 publications

(3 citation statements)

References 5 publications

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“…Further, metformin in presence of diazepam exhibited pronounced antihyperglycemic and antihypertriglyceridaemic effect than metformin monotherapy in cooccurring T2DM and stress exposed rats. In an earlier report, it has been documented that diazepam treatment augmented the hyperglycemic condition in hyperglycemic rats and this effect was ameliorated with metformin administration [29]. However, in the present study diazepam did not alter the hyperglycemic condition in the cooccurring condition of T2DM and stress.…”

Section: Discussioncontrasting

confidence: 76%

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Diazepam Potentiates the Antidiabetic, Antistress and Anxiolytic Activities of Metformin in Type-2 Diabetes Mellitus with Cooccurring Stress in Experimental Animals

Garabadu

Krishnamurthy

2014

BioMed Research International

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Psychological stress is considered as one of the limiting factors in the management of type-2 diabetes mellitus (T2DM). Therefore, the basic objective of the present study was to evaluate the antidiabetic effect of metformin, diazepam, and their combination in cooccurring T2DM and stress condition (DMS). T2DM was induced in the male rats by administering streptozotocin (45 mg/kg, i.p.) and nicotinamide (110 mg/kg, i.p.) with time lag of 15 min. Rats were subjected to two sessions of cold restraint stress paradigm for one hour on the sixth and seventh day after streptozotocin injection. Administration of metformin (25 mg/kg, p.o.) and diazepam (1 mg/kg, p.o.) in combination from the seventh to thirteenth day after streptozotocin injection showed better improvement in glucose tolerance and insulin sensitivity compared to monotherapy of either drug. In addition, the combination significantly attenuated DMS-induced hyperglycemia, hypertriglyceridaemia, hypercorticosteronemia, anxiety-like behavior, and insulin resistance through modulating insulin signaling pathway in the liver compared to monotherapy. Further, improvement of mitochondrial function, integrity, and oxidative stress in hippocampus, hypothalamus, prefrontal cortex, striatum, amygdala, and nucleus accumbens was observed with the combination. Therefore, metformin in combination with diazepam may be a better therapeutic option in the management of T2DM with cooccurring stress condition.

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Section: Discussioncontrasting

confidence: 76%

“…Diazepam is widely prescribed for the treatment of anxiety, insomnia, or stress disorders. Diazepam augmented the blood glucose level in hyperglycemic rats; however, it did not alter the same in presence of metformin in the animals [29]. Thus, the antihyperglycemic activity of metformin is not impaired in the presence of diazepam.…”

Section: Introductionmentioning

confidence: 99%

Diazepam Potentiates the Antidiabetic, Antistress and Anxiolytic Activities of Metformin in Type-2 Diabetes Mellitus with Cooccurring Stress in Experimental Animals

Garabadu

Krishnamurthy

2014

BioMed Research International

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“…But diazepam may alter insulin secretion and insulin sensitivity after a single administration in healthy volunteers [34], and diazepam-induced hyperglycemia, might be related to changes in serum chromium levels [35]. However in this study the increase in glycemia in diabetic women would be the result of the stress due to operation rather than diazepam treatment.…”

Section: Discussionmentioning

confidence: 90%

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

Lalić-Popović

Paunkovic

Grujić

et al. 2013

BMC Pregnancy Childbirth

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BackgroundPrevious studies carried out in our laboratories have demonstrated impaired drug permeation in diabetic animals. In this study the permeation of diazepam (after a single dose of 5 mg/day, administered intramuscularly) will be investigated in diabetic and hypertensive pregnant women.MethodsA total 75 pregnant women were divided into three groups: group 1 (healthy control, n = 31), group 2 (diabetic, n = 14) and group 3 (hypertensive, n = 30). Two sets of diazepam plasma concentrations were collected and measured (after the administration of the same dose of diazepam), before, during and after delivery. The first set of blood samples was taken from the mother (maternal venous plasma). The second set of samples was taken from the fetus (fetal umbilical venous and arterial plasma). In order to assess the effect of diabetes and hypertension on diazepam placental-permeation, the ratios of fetal to maternal blood concentrations were determined. Differences were considered statistically significant if p ≤ 0.05.ResultsThe diabetes and hypertension groups have 2-fold increase in the fetal umbilical-venous concentrations, compared to the maternal venous concentrations. Feto: maternal plasma-concentrations ratios were higher in diabetes (2.01 ± 1.10) and hypertension (2.26 ± 1.23) groups compared with control (1.30 ± 0.48) while, there was no difference in ratios between the diabetes and hypertension groups. Umbilical-cord arterial: venous ratios (within each group) were similar among all groups (control: 0.97 ± 0.32; hypertension: 1.08 ± 0.60 and diabetes: 1.02 ± 0.77).ConclusionsOn line with our previous findings which demonstrate disturbed transcellular trafficking of lipophilic drugs in diabetes, this study shows significant increase in diazepam placental-permeation in diabetic and hypertensive pregnant women suggesting poor transcellular control of drug permeation and flux, and bigger exposure of the fetus to drug-placental transport.

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The effects of different anaesthetic treatments on the adreno-cortical functions and glucose levels in NZW rabbits

Illera

Gil

Silván

et al. 2000

J. Physiol. Biochem.

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The effects of five anaesthetics on the corticosterone, cortisol and glucose concentrations were investigated in the NZW rabbit. Sixty animals were assigned to 6 treatment groups (n= 10 per group): control ( iv saline solution injection), ketamine (10 mg/kg iv) with either xylazine (3 mg/kg iv) or diazepam (2 mg/kg iv), pentobarbitone (30 mg/kg iv), thiopentone (20 mg/kg iv) and fentanyl/droperidol (1 mg/kg sc). Plasma glucocorticoids were measured by competitive enzymeimmunoassay EIA and glucose by an autoanalyzer, previously validated for this species in both cases. Blood samples were obtained at 6 time-points: before injection, at 10, 30, 60, 120 min and 24 h after injection of the anaesthetics/saline. A significant decrease of plasma glucocorticoids at 10-60 min was observed in the pentobarbitone and fentanyl/ droperidol groups, whereas the administration of ketamine/diazepam or thiopentone stimulated plasma glucocorticoid release, principally in the recovery period. However, in the ketamine/xylazine group no changes were observed in the glucocorticoid levels, except for a significative increase of cortisol at 60-120 min. Glucose levels significantly increased after ketamine/diazepam administration and principally, after ketamine/xylazine treatment. The present data suggest that ketamine/xylazine has little effect on glucocorticoid levels and provides an adequate level of surgical anaesthesia, hence it would be the anaesthetic of choice, although the hyperglycaemic effect after injection has to be considered for any experimental procedures in rabbits.

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Interaction between diazepam and oral antidiabetic agents on serum glucose, insulin and chromium levels in rats

Cited by 7 publications

References 5 publications

Diazepam Potentiates the Antidiabetic, Antistress and Anxiolytic Activities of Metformin in Type-2 Diabetes Mellitus with Cooccurring Stress in Experimental Animals

Diazepam Potentiates the Antidiabetic, Antistress and Anxiolytic Activities of Metformin in Type-2 Diabetes Mellitus with Cooccurring Stress in Experimental Animals

Diabetes and hypertension increase the placental and transcellular permeation of the lipophilic drug diazepam in pregnant women

The effects of different anaesthetic treatments on the adreno-cortical functions and glucose levels in NZW rabbits

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