Comparative effectiveness of carvedilol and propranolol on glycemic control and insulin resistance associated with L-thyroxin-induced hyperthyroidism--an experimental study.
The present study was undertaken to investigate the effectiveness of adrenergic antagonists carvedilol and propranolol on L-thyroxin-induced cardiovascular and metabolic disturbances in rats. Treatment with L-thyroxin sodium (75 mg/kg body mass, s.c., every alternate day for 3 weeks), produced a significant increase in food and water intake, body temperature, heart rate, systolic blood pressure, along with an increase in serum T3, T4, and triglyceride levels. Besides a significant reduction in body mass, serum levels of TSH and cholesterol were also reduced following L-thyroxin treatment. Carvedilol (10 mg/kg body mass, orally) and propranolol (10 mg/kg body mass, i.p.) administered daily in the third week to 2 separate groups of L-thyroxin-treated animals reversed thyroxin-induced loss in body mass and rise in body temperature, blood pressure, and heart rate. Propranolol treatment increased TSH levels and decreased T3 and T4 levels in hyperthyroid animals, whereas carvedilol did not produce any effect on thyroid hormones. Carvedilol treatment reversed thyroxin induced hypertriglyceridemia, whereas propranolol treatment had no effect. Both carvedilol and propranolol prevented decrease in cholesterol levels induced by thyroxine. Compared with normal animals, L-thyroxin-treated animals showed a state of hyperglycemia, hyperinsulinaemia, impaired glucose tolerance, and insulin resistance, as inferred from elevated fasting serum glucose and insulin levels, higher area under the curve over 120 min for glucose, and decreased insulin sensitivity index (KITT). Propranolol and carvedilol treatment significantly decreased fasting serum glucose levels. Treatment with propranolol did not alter serum insulin levels, area-under-the-curve glucose, or KITT values. However, treatment with carvedilol significantly reduced area-under-the-curve glucose, decreased fasting serum insulin levels and significantly increased KITT values. In conclusion, carvedilol appears to produce favorable effects on insulin sensitivity and glycemic control and can therefore be considered as more efficacious adjunctive treatment than propranolol in hyperthyroidism.
Bhatt
Parloop
P
Department of Pharmacology, L.M. College of Pharmacy, Navarangpura, Ahmedabad-380009, Gujarat, India. parloop72@rediffmail.com
Makwana
Dharmesh
D
Santani
Devdas
D
Goyal
Ramesh
R
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001066:Appetite / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D001831:Body Temperature / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology* / Q000627:therapeutic use; D000077261:Carvedilol; D002784:Cholesterol / Q000097:blood; D005215:Fasting / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D006946:Hyperinsulinism / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D006980:Hyperthyroidism / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D011412:Propanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000633:toxicity; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D002227:Carbazoles; D007328:Insulin; D011412:Propanolamines; D014280:Triglycerides; D014284:Triiodothyronine; D000077261:Carvedilol; D013972:Thyrotropin; D002784:Cholesterol; D011433:Propranolol; D013974:Thyroxine