The effect of repaglinide on insulin secretion and oxidative stress in type 2 diabetic patients

Tankova, Tsvetalina; Koev, D; Dakovska, Lilia; Кirilov, Georgi

doi:10.1016/s0168-8227(02)00179-1

Cited by 42 publications

(32 citation statements)

References 37 publications

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“…At the same time, the enzyme activity was partly elevated. In the literature, an increase in the enzyme activity after repaglinide was observed in the serum of type 2 diabetic patients [25]. SOD activity was also normalized by gliclazide in the red blood cells of diabetic patients [31] and by glyburide in tissues of diabetic animals [32].…”

Section: Discussionmentioning

confidence: 89%

“…Pioglitazone, an agonist of nuclear peroxisome proliferator-activated receptor γ (PPARγ), was shown to affect some parameters of oxidative stress [19][20][21][22]. Some positive effects were also observed after addition of repaglinide, a short acting blocker of beta cell K AT P channels [23][24][25]. Hence, the final aim of the present study was to examine whether these two different oral antidiabetics could affect the oxidative DNA damage and Cu,Zn-SOD metabolism in the kidney of diabetic animals.…”

Section: Introductionmentioning

confidence: 93%

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DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide

et al. 2006

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Abstract:In the present study, DNA oxidative damage was elevated and superoxide dismutase (Cu,Zn-SOD) metabolism was disturbed in the kidney of alloxan-induced diabetic animals. The effects of pioglitazone and repaglinide, new oral antidiabetics, on 8-hydroxy-2'-deoxyguanosine (8-OHdG) and Cu,Zn-SOD were studied. Diabetic versus control levels (mean ± SE) of 8-OHdG were 24.9 ± 0.2 vs. 21.8 ± 0.1 and 21.5 ± 0.2 vs 20.1 ± 0.2 pmol/µg DNA after 4 and 8 weeks, respectively. At p<0.05, pioglitazone diminished this parameter in diabetic animals (22.0 ± 0.2 and 20.1 ± 0.3 pmol/µg DNA). The level was not affected in diabetic groups receiving repaglinide (24.9 ± 0.2 and 21.5 ± 0.3 pmol/µg DNA). In diabetic kidney, Cu,Zn-SOD mRNA was diminished relative to control animals and was modulated by pioglitazone and repaglinide treatments. Simultaneously, Cu,Zn-SOD activity was also diminished (1.5 ± 0.2 vs. 2.8 ± 0.3 and 1.8 ± 0.1 vs 2.9 ± 0.3 U/mg protein after 4 and 8 weeks, respectively) and partly changed after pioglitazone (2.1 ± 0.4 and 2.3 ± 0.3 U/mg protein) and repaglinide (2.0 ± 0.1 and 2.4 ± 0.2 U/mg protein). These results suggest that a reduction in oxidative stress in diabetic kidney can be achieved with the administration of pioglitazone and to some extent using repaglinide treatment.

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 93%

DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide

et al. 2006

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“…It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release (1). It has been reported that RG treatment decreases the concentration of lipid hydroperoxide (LPO) and increases the activity of superoxide dismutase (SOD) in kidneys of diabetic nephropathy (2)(3)(4)(5)(6). Cyclosporine A (CsA) is a drug used to treat many autoimmune diseases and to prevent transplant rejection.…”

Section: Introductionmentioning

confidence: 99%

Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression

Jin¹,

Li²,

Li³

et al. 2018

Turk J Med Sci

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IntroductionRepaglinide (RG) is an oral antihyperglycemic agent used for the treatment of noninsulin-dependent diabetes mellitus. It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release (1). It has been reported that RG treatment decreases the concentration of lipid hydroperoxide (LPO) and increases the activity of superoxide dismutase (SOD) in kidneys of diabetic nephropathy (2-6). Cyclosporine A (CsA) is a drug used to treat many autoimmune diseases and to prevent transplant rejection. Nephrotoxicity constitutes its main adverse effect and can cause acute or chronic kidney damage (7). Many studies demonstrated that CsA-induced nephrotoxicity is mediated by oxidative damage (8-10). Our recent study showed that RG plays an important role in CsA-induced nephrotoxicity through its antioxidant properties (11).Other studies showed that CsA-induced cytotoxicity was related to apoptosis in renal tubular or endothelial cells (12,13). It is not known, however, whether RG has any effect on CsA-induced renal tubular apoptosis by affecting the expression of apoptosis-associated proteins. Therefore, the purpose of the present study was to investigate the effects of RG on CsA-induced renal tubular apoptosis, and the expression of Bax and Bcl-2 proteins in rats. Materials and methods Animals and treatmentAdult male Sprague Dawley rats weighing 250-300 g were used. The animals were obtained from the Experimental Research Centre, Wuhan, China. The animals were maintained at 25 °C in a room with a 12/12 light/dark cycle and had free access to water and food.Forty rats were randomly allocated into 4 groups (n = 10). Olive oil (1 mL) was administered by gavage (IG) to Background/aim: Repaglinide (RG) is a prandial glucose regulator used for the treatment of type 2 diabetes. Our recent study showed that RG plays an important role in cyclosporine A (CsA)-induced nephrotoxicity through its antioxidant properties. However, it is not known whether or not RG has any protective effect on CsA-induced renal tubular toxicity by affecting apoptosis and expression of apoptosis-associated protein. The purpose of this study was to investigate the effects of RG on CsA-induced renal tubule apoptosis and Bax and Bcl-2 protein expression in rats.Materials and methods: Forty male Sprague Dawley rats weighing 250-300 g were randomly divided into four groups: administrations of olive oil (control, per os (PO)), CsA (30 mg/kg in olive oil, subcutaneous (SC)), and RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil, SC) every day for 15 days. Results:Our results showed that SC administration of CsA (30 mg/kg) to rats produced marked injury and apoptosis, elevation of Bax protein expression, and inhibition of Bcl-2 protein expression in the kidneys, which were reversed significantly by oral administration of RG (0.2 or 0.4 mg/kg). Conclusion:The findings of our study indicate that RG may play an important role in protecting the kidneys through inhibiting ...

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“…There had been reported antioxidative and anti-inflammatory effects of repaglinide in diabetic animals and patients [7][8][9][10] . Part of these anti-inflammatory effects might be secondary to repaglinide's effect on modulating the diabetes.…”

Section: Introductionmentioning

confidence: 99%

Novel Anti-Inflammatory Effects of Repaglinide in Rodent Models of Inflammation

Tung¹,

Cheung²,

Ciallella

et al. 2011

Pharmacology

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Background: Repaglinide is an FDA-approved treatment for type 2 diabetes mellitus. The anti-inflammatory effect of repaglinide in the absence of diabetes has not been reported previously. It is the objective of this set of studies to investigate the potential anti-inflammatory effects of repaglinide. Method: The in vivo anti-inflammatory effects of repaglinide were studied in two different models of delay type hyperreactivity (DTH) response induced by sheep red blood cells (sRBC) and 2,5′-dinitrofluorobenzene (DNFB), and in two different rodent models of lipopolysaccharide (LPS) challenge. Results: In mice systemically sensitized with sRBC, which subsequently received a local injection of sRBC in the footpad, local swelling occurred within 24 h after challenge. Repaglinide was efficacious in attenuating this response. In an orthogonal DTH model using DNFB as the antigen, the animals received topical sensitization with DNFB on their shaved backs, followed by topical challenge on the left ears. Repaglinide efficaciously downregulated the resulting ear swelling response. In mice challenged systemically or intratracheally with LPS, repaglinide significantly decreased serum tumor necrosis factor α level and bronchial alveolar lavage fluid MCP-1 levels, respectively. Conclusion: This set of data suggests novel anti-inflammatory effects of repaglinide in nondiabetic animals. However, the high dose required for an efficacious effect would make this application impractical in the clinic.

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The effect of repaglinide on insulin secretion and oxidative stress in type 2 diabetic patients

Cited by 42 publications

References 37 publications

DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide

DNA oxidation and superoxide dismutase in the kidney of diabetic animals: effects of pioglitazone and repaglinide

Repaglinide inhibits cyclosporine A-induced renal tubular toxicity by affecting apoptosis and Bax and Bcl-2 expression

Novel Anti-Inflammatory Effects of Repaglinide in Rodent Models of Inflammation

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