Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats

Majithiya, Jayesh B.; Balaraman, R

doi:10.1016/j.lfs.2005.10.020

Cited by 96 publications

(74 citation statements)

References 39 publications

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“…In line with the above study, in our animal model, invasive blood pressure measurement showed an increase in MAP and Ang II-induced ⌬MAP, which could not be reversed upon diet reversal. Metformin has been reported to have an anti-hypertensive effect in diabetes (31). Our study also found that metformin significantly mitigated the basal as well as the Ang IIinduced MAP elevation.…”

Section: Discussionsupporting

confidence: 80%

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Tikoo

Sharma

Amara

et al. 2016

Journal of Biological Chemistry

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Section: Discussionsupporting

confidence: 80%

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Tikoo

Sharma

Amara

et al. 2016

Journal of Biological Chemistry

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“…[32][33][34] Summarizing, these results allow us to suggest that n-STZ diabetes leads to an increase in superoxide levels, which could contribute to an impaired NO vasodilator-dependent responses found previously. 19) Corroborating with our in vivo data, Majithiya et al (2006) 35) showed an increase in superoxide concentration in aorta of adult STZ-induced diabetic rats.…”

Section: Discussionsupporting

confidence: 67%

Constrictor Responses to Noradrenaline, Hemodynamic Profile, and Superoxide Levels Measured by Hydroethidine Oxidation in Diabetic Rats

Sartoretto

Oliveira

Nigro

et al. 2007

Biological & Pharmaceutical Bulletin

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Vascular complications are more frequent and severe among diabetics as compared with healthy populations. 1-3)Cardiovascular disease is one of the leading causes of death in the Western world and diabetes mellitus is a major factor underlying its development.4) The pathogenesis of diabetesassociated hypertension is not completely understood, but may involve insulin resistance, which is associated with hypertension in both diabetic and non-diabetic individuals. 5,6) Most of the complications in diabetes are due to increased serum glucose and increased generation of oxygen-derived free radicals, which lead to endothelial dysfunction. Prolonged exposure to hyperglycemia is recognized as a major factor in the pathogenesis of atherosclerosis in diabetic patients, by inducing a large number of alterations at the cellular level of vascular tissue.7) The most important mechanisms involved in this process are glycation end products accumulating in vessel wall 8) and oxidative stress by impairment of oxidative defensive capacity as well as by an overproduction of reactive oxygen species (ROS). 9-11)The neonatal streptozotocin (n-STZ) rat model firstly described by Portha et al. (1974) 12) ; Weir et al. (1981) 13) is an alternate model that presents pancreatic b-cell destruction followed by partial b-cell regeneration and glucose intolerance.14) Other authors confirmed these findings and showed that neonatally-STZ treated rats in adulthood display some of the typical characteristics of diabetes. [15][16][17][18] We demonstrated in a previous study that responses of mesenteric microvessels of n-STZ diabetic rats to endothelium-dependent vasodilator acetylcholine and to sodium nitroprusside, an endothelium-independent vasodilator, were significantly reduced compared with non-diabetic rats. We concluded that the impaired vasodilatation is, in part, due to a reduced sensitivity of vessels to NO and to a reduced production and/or bioavailability of NO. 19) Reduction in bioavailability and/or sensitivity of NO in n-STZ diabetic rats may be causing several other alterations in vascular function. Therefore, the goal of the present study was to test the hypothesis that vascular dysfunction in neonatal streptozotocin-induced diabetic rats could be associated with alterations in blood pressure, hemodynamic profile, and levels of superoxide anion. MATERIALS AND METHODS Induction of DiabetesDiabetes mellitus was induced in male newborn (2-d-old, weighing 8 to 10 g) Wistar rats with bolus injection of STZ (160 mg/kg, i.p.) dissolved in citrate buffer (10 mM, pH 4.5). Control rats were sham injected with the same volume of citrate buffer. The n-STZ diabetic rats and matching controls were housed according to institutional guidelines (room temperature 22Ϯ0.5°C, 12 h light/dark cycle, 60% humidity, standard rat chow and water ad libitum). The experimental protocols were approved and performed in accordance with the guidelines of the Institute of Biomedical Sciences Ethical Committee.Characterization of the n-STZ Diabetic Rats The n-ST...

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“…Recently, Majithiya and Balaraman [34] reported that metformin protects liver, kidney and aorta tissues against lipid peroxidation promoted by streptozotocin-induced diabetes. It has also been shown that metformin decreases the level of lipid peroxidation markers in low-density and high-density lipoprotein particles obtained from adult type 2 diabetic patients [35].…”

Section: Discussionmentioning

confidence: 99%

Metformin promotes isolated rat liver mitochondria impairment

et al. 2007

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Metformin, a drug widely used in the treatment of type 2 diabetes, has recently received attention due to the new and contrasting findings regarding its effects on mitochondrial function. In the present study, we evaluated the effect of metformin in isolated rat liver mitochondria status. We observed that metformin concentrations ‡8 mM induce an impairment of the respiratory chain characterized by a decrease in RCR and state 3 respiration. However, only metformin concentrations ‡10 mM affect the oxidative phosphorylation system by decreasing the mitochondrial transmembrane potential and increasing the repolarization lag phase. Moreover, our results show that metformin does not prevent H 2 O 2 production, neither protects against lipid peroxidation induced by the prooxidant pair ADP/Fe 2+ . In addition, we observed that metformin exacerbates Ca 2+ -induced permeability transition pore opening by decreasing the capacity of mitochondria to accumulate Ca 2+ and increasing the oxidation of thiol groups. Taken together, our results show that metformin can promote liver mitochondria injury predisposing to cell death.

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Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats

Cited by 96 publications

References 39 publications

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Constrictor Responses to Noradrenaline, Hemodynamic Profile, and Superoxide Levels Measured by Hydroethidine Oxidation in Diabetic Rats

Metformin promotes isolated rat liver mitochondria impairment

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