title: Glucose handling in streptozotocin-induced diabetic rats is improved by tyramine but not by the amine oxidase inhibitor semicarbazide.
abstract: A soluble form of semicarbazide-sensitive amine oxidase (SSAO) circulating in plasma is known to increase in type 1 and 2 diabetes. This cuproenzyme generates hydrogen peroxide, ammonia, and aldehydes when oxidizing circulating biogenic or exogenous amines. Based on the angiotoxicity of these products, inhibition of SSAO has been proposed to prevent vascular complications of diabetes. However, substrates of SSAO and monoamine oxidase (MAO) have been recently evidenced to activate glucose utilisation in insulin-sensitive tissues and to exhibit antihyperglycemic actions. To determine whether amine oxidase blockade or activation could be beneficial for diabetes, we aimed at comparing the influence of prolonged treatments with semicarbazide (SSAO-inhibitor), pargyline (MAO-inhibitor), or tyramine (amine oxidase substrate) on amine oxidase activities and glycemic control in streptozotocin-induced diabetic rats. The increase in plasma SSAO was confirmed in diabetic rats, while MAO and SSAO were decreased in subcutaneous adipose tissue when compared with normoglycemic controls. Among the diabetic rats, only those receiving tyramine exhibited slightly decreased hyperglycemia and improved glucose tolerance. Adipocytes from untreated or treated diabetic rats shared similar sensitivity to insulin. However glucose uptake activation and lipolysis inhibition in response to amine oxidase substrates combined with vanadate were impaired in rats treated with amine oxidase inhibitors. Thus, amine oxidase inhibition does not improve metabolic control while prolonged administration of tyramine slightly improves glucose disposal. It is therefore concluded that amine oxidase activation by increased substrate supply elicits insulin-like actions that may be more beneficial in diabetes than SSAO inhibition formerly proposed to prevent vascular complications.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U586, IFR 31, Bat. L3, CHU Rangueil, Toulouse, France.
authors.forename: Virgile
authors.initials: V
authors.lastname: Visentin
authors.forename: Sandy
authors.initials: S
authors.lastname: Bour
authors.forename: Jérémie
authors.initials: J
authors.lastname: Boucher
authors.forename: Danielle
authors.initials: D
authors.lastname: Prévot
authors.forename: Philippe
authors.initials: P
authors.lastname: Valet
authors.forename: Catherine
authors.initials: C
authors.lastname: Ordener
authors.forename: Angelo
authors.initials: A
authors.lastname: Parini
authors.forename: Christian
authors.initials: C
authors.lastname: Carpéné
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood / Q000378:metabolism; D000818:Animals; D001596:Benzylamines / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008066:Lipolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008995:Monoamine Oxidase / Q000097:blood / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009206:Myocardium / Q000201:enzymology; D010084:Oxidation-Reduction / Q000187:drug effects; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012663:Semicarbazides / Q000494:pharmacology*; D014439:Tyramine / Q000378:metabolism / Q000494:pharmacology*; D014638:Vanadates / Q000494:pharmacology
chemical_list: D001596:Benzylamines; D001786:Blood Glucose; D008996:Monoamine Oxidase Inhibitors; D012663:Semicarbazides; C010059:carbamylhydrazine; D014638:Vanadates; D010293:Pargyline; C030796:benzylamine; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D005947:Glucose; D014439:Tyramine