Increases of spinal kinin receptor binding sites in two rat models of insulin resistance.
An autoradiographic study was conducted to determine whether kinin receptors are altered in the rat spinal cord in two experimental models of chronic hyperglycemia and insulin resistance. Sprague-Dawley rats were given 10% d-glucose in their drinking water alone or with insulin (9 mU/kg/min with osmotic pumps) for 4 weeks. Both groups and control rats were treated either with a normal chow diet or with an alpha-lipoic acid-supplemented diet as antioxidant therapy. After 4 weeks of treatment, glycemia, insulinemia, blood pressure, insulin resistance index, the production of superoxide anion in the aorta and the density of B2 receptor binding sites in the dorsal horn were significantly increased in the two models. These effects were prevented or attenuated by alpha-lipoic acid. In contrast, B2 receptor binding sites of most spinal cord laminae were increased in the glucose group only and were not affected by alpha-lipoic acid. Results show that chronic hyperglycemia associated with insulin resistance increases B1 and B2 receptor binding sites in the rat spinal cord through distinct mechanisms, including the oxidative stress for the B1 receptor.
El Midaoui
Adil
A
Department of Physiology, Faculty of Medicine, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, Que., Canada H3C 3J7.
Ongali
Brice
B
Petcu
Mihai
M
Rodi
Donata
D
de Champlain
Jacques
J
Neugebauer
Witold
W
Couture
Réjean
R
D000818:Animals; D001665:Binding Sites; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000187:drug effects / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D013481:Superoxides; D008063:Thioctic Acid; D005947:Glucose