Amelioration of corticosteroid-induced type 2 diabetes mellitus by rosiglitazone is possibly mediated through stimulation of thyroid function and inhibition of tissue lipid peroxidation in mice.
We investigated the possible involvement of thyroid hormones and lipid peroxidation in the antidiabetic potential of rosiglitazone (a peroxisome proliferator-activated receptors gamma-agonist) on corticosteroid-induced type 2 diabetes mellitus. Rosiglitazone was administered to dexamethasone-induced hyperglycaemic male mice and the alterations in serum concentrations of thyroid hormones insulin, total cholesterol, triglycerides and fasting glucose were studied. Simultaneously changes in lipid peroxidation, reduced glutathione (GSH) content, superoxide dismutase and catalase activities in renal and cardiac tissues (which are commonly affected in diabetes mellitus), were also investigated. Administration of dexamethasone (1.0 mg/kg/day intramuscularly for 28 days) caused hyperglycaemia with a parallel increase in serum insulin, total cholesterol, triglycerides and tissue lipid peroxidation with a decrease in serum levels of both the thyroid hormones (triiodothyronine, T(3) and thyroxine, T(4)) and in the activity of associated tissue antioxidants such as superoxide, catalase and glutathione. However, rosiglitazone administration (3.2 mg/kg/day orally for 21 days) along with an equivalent amount of dexamethasone reverted most of these changes, including a marked inhibition of tissue lipid peroxidation and an increase in the serum levels of both thyroid hormones. The present findings reveal that the test drug ameliorates corticosteroid-induced type 2 diabetes mellitus through an increase in serum thyroid hormone concentrations and inhibition in tissue lipid peroxidation.
Jatwa
Rameshwar
R
Thyroid Research Unit, School of Life Sciences, Devi Ahilya University, Takshashila Campus, Indore, India. rjatwa80@hotmail.com
Parmar
Hamendra Singh
HS
Panda
Sunanda
S
Kar
Anand
A
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003907:Dexamethasone; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D005978:Glutathione / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D000077154:Rosiglitazone; D013482:Superoxide Dismutase / Q000378:metabolism; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013974:Thyroxine / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D014284:Triiodothyronine; D003907:Dexamethasone; D002784:Cholesterol; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D013974:Thyroxine