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Inhibition of renal gluconeogenesis contributes to hypoglycaemic action of NADPH oxidase inhibitor, apocynin.
Chem Biol Interact. 2011 Jan 15; 189(1-2):119-26.CB

Abstract

NADPH oxidase, catalysing superoxide radical (O₂(.-)) formation, is considered as a main source of reactive oxygen species in kidneys and its increased activity is supposed to be involved in the development of diabetic nephropathy. The aim of this study was to investigate the effect of NADPH oxidase inhibitor, apocynin, on renal gluconeogenesis, which is an important source of endogenous glucose under diabetic conditions. The following observations were made during the experiments performed on isolated renal proximal tubules of control and alloxan diabetic rabbits: (1) apocynin (200 μM) inhibited the rate of glucose synthesis by 45-80%, depending on the substrate applied; (2) the rate of glucose production was also significantly diminished in the presence of TEMPOL (5mM), a superoxide radical scavenger, suggesting that the decrease in O₂(.-) formation might be involved in apocynin-evoked gluconeogenesis inhibition; (3) the activities of phosphoenolpyruvate carboxykinase (PEPCK) and/or aldolase were lowered in the presence of either apocynin or TEMPOL, as concluded from the intracellular levels of gluconeogenic intermediates. The data from in vivo experiments indicated that apocynin treatment (2g/l of drinking water): (1) significantly (by about 30%) attenuated serum glucose concentration in diabetic rabbits and did not affect glycaemia in control animals; (2) normalized diabetes-stimulated rate of glucose synthesis and slightly inhibited gluconeogenesis in control rabbits; (3) normalized diabetes-increased activity of mitochondrial PEPCK and lowered cytosolic PEPCK activity by about 20% below the value for untreated control animals; (4) slightly decreased the activity of mitochondrial PEPCK and did not change the activity of cytosolic one in control rabbits. Thus, it is concluded that: (1) the inhibition of NADPH oxidase might contribute to lowered rate of renal gluconeogenesis, probably due to decreasing PEPCK activity; (2) inhibition of renal gluconeogenesis is involved in apocynin hypoglycaemic action in vivo; (3) apocynin might be beneficial for diabetes treatment.

Authors+Show Affiliations

Department of Metabolic Regulation, Institute of Biochemistry, University of Warsaw, I. Miecznikowa 1, Warsaw, Poland.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20934416

Citation

Winiarska, Katarzyna, et al. "Inhibition of Renal Gluconeogenesis Contributes to Hypoglycaemic Action of NADPH Oxidase Inhibitor, Apocynin." Chemico-biological Interactions, vol. 189, no. 1-2, 2011, pp. 119-26.
Winiarska K, Grabowski M, Rogacki MK. Inhibition of renal gluconeogenesis contributes to hypoglycaemic action of NADPH oxidase inhibitor, apocynin. Chem Biol Interact. 2011;189(1-2):119-26.
Winiarska, K., Grabowski, M., & Rogacki, M. K. (2011). Inhibition of renal gluconeogenesis contributes to hypoglycaemic action of NADPH oxidase inhibitor, apocynin. Chemico-biological Interactions, 189(1-2), 119-26. https://doi.org/10.1016/j.cbi.2010.09.033
Winiarska K, Grabowski M, Rogacki MK. Inhibition of Renal Gluconeogenesis Contributes to Hypoglycaemic Action of NADPH Oxidase Inhibitor, Apocynin. Chem Biol Interact. 2011 Jan 15;189(1-2):119-26. PubMed PMID: 20934416.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of renal gluconeogenesis contributes to hypoglycaemic action of NADPH oxidase inhibitor, apocynin. AU - Winiarska,Katarzyna, AU - Grabowski,Michal, AU - Rogacki,Maciej K, Y1 - 2010/10/08/ PY - 2010/08/27/received PY - 2010/09/30/accepted PY - 2010/10/12/entrez PY - 2010/10/12/pubmed PY - 2011/3/2/medline SP - 119 EP - 26 JF - Chemico-biological interactions JO - Chem Biol Interact VL - 189 IS - 1-2 N2 - NADPH oxidase, catalysing superoxide radical (O₂(.-)) formation, is considered as a main source of reactive oxygen species in kidneys and its increased activity is supposed to be involved in the development of diabetic nephropathy. The aim of this study was to investigate the effect of NADPH oxidase inhibitor, apocynin, on renal gluconeogenesis, which is an important source of endogenous glucose under diabetic conditions. The following observations were made during the experiments performed on isolated renal proximal tubules of control and alloxan diabetic rabbits: (1) apocynin (200 μM) inhibited the rate of glucose synthesis by 45-80%, depending on the substrate applied; (2) the rate of glucose production was also significantly diminished in the presence of TEMPOL (5mM), a superoxide radical scavenger, suggesting that the decrease in O₂(.-) formation might be involved in apocynin-evoked gluconeogenesis inhibition; (3) the activities of phosphoenolpyruvate carboxykinase (PEPCK) and/or aldolase were lowered in the presence of either apocynin or TEMPOL, as concluded from the intracellular levels of gluconeogenic intermediates. The data from in vivo experiments indicated that apocynin treatment (2g/l of drinking water): (1) significantly (by about 30%) attenuated serum glucose concentration in diabetic rabbits and did not affect glycaemia in control animals; (2) normalized diabetes-stimulated rate of glucose synthesis and slightly inhibited gluconeogenesis in control rabbits; (3) normalized diabetes-increased activity of mitochondrial PEPCK and lowered cytosolic PEPCK activity by about 20% below the value for untreated control animals; (4) slightly decreased the activity of mitochondrial PEPCK and did not change the activity of cytosolic one in control rabbits. Thus, it is concluded that: (1) the inhibition of NADPH oxidase might contribute to lowered rate of renal gluconeogenesis, probably due to decreasing PEPCK activity; (2) inhibition of renal gluconeogenesis is involved in apocynin hypoglycaemic action in vivo; (3) apocynin might be beneficial for diabetes treatment. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/20934416/Inhibition_of_renal_gluconeogenesis_contributes_to_hypoglycaemic_action_of_NADPH_oxidase_inhibitor_apocynin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(10)00579-X DB - PRIME DP - Unbound Medicine ER -