Reactive oxygen species facilitate the insulin-dependent inhibition of glucagon-induced glucose production in the isolated perfused rat liver.
Recent studies indicate that intracellular insulin signalling involves the formation of reactive oxygen species (ROS) by NADPH oxidases (NOX). ROS inhibit intracellular protein tyrosin phosphatases whereby phosphoprotein signalling is enhanced and prolonged. We used the isolated perfused rat liver and detected ROS formation by measuring the surface fluorescence at wavelengths specific for the intracellular ROS sensor carboxydihydrodichlorofluorescein. Insulin (2, 5, 20 nM) induced low level ROS formation that was abolished by the NOX inhibitor diphenyleneiodonium chloride (4 microM). Studying insulin-dependent inhibition of glucagon-activated glucose production showed that melatonin (50 microM), used as ROS scavenger, inhibited ROS formation and blunted the effect of insulin on glucose production. The data support the general notion that hormone-dependent ROS formation modifies intracellular signal transduction.
Messner
Jürgen
J
Department of Pathophysiology, Medical University of Vienna, Vienna, Austria. juergen.messner@meduniwien.ac.at
Graf
Jürg
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005934:Glucagon / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D008297:Male; D008550:Melatonin / Q000502:physiology; D019255:NADPH Oxidases / Q000502:physiology; D009924:Organ Culture Techniques; D010750:Phosphoproteins / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D005934:Glucagon; D019255:NADPH Oxidases; D011505:Protein-Tyrosine Kinases; D008550:Melatonin