Metabolic effects of thioctic acid in rodent models of insulin resistance and diabetes.
1. The antioxidant thioctic acid (TA) has been used in the treatment of diabetic neuropathy and recent studies have suggested that TA also has pancreatic and peripheral effects that improve glucose transport and metabolism. In the present study, the metabolic effects of TA were evaluated in rodent models of insulin resistance (fructose-fed Sprague-Dawley rat) and insulin deficiency (streptozotocin (STZ)-induced diabetic rat). Oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in conscious rats after treatment with 50 mg/kg per day TA or vehicle for 5 days. 2. Fructose feeding for 7 days induced insulin resistance and impaired glucose tolerance and hypertriglycerideaemia. Treatment of fructose-fed rats with TA had no significant effect on fasting or stimulated glucose levels or on fasting triglyceride concentrations (e.g. the area under the curve for glucose (AUCglu) following OGTT was 1233 +/- 67 and 1284 +/- 59 in fructose-fed rats treated with either TA (n = 12) or vehicle (n = 12), respectively). Similarly, TA had no significant effect on IVGTT profiles in fructose-induced insulin resistance. 3. Low-dose STZ (80 mg/kg, i.p., over 2 days) induced hyperglycaemia, but TA had no significant glucose-lowering effects in STZ-diabetic rats (AUCglu (OGTT) following oral administration was 5507 +/- 27 and 5450 +/- 27 in TA (n = 12) and vehicle-treated (n = 12) rats, respectively). Nor did pretreatment with TA affect the diabetogenic response to STZ. 4. In contrast with previous in vitro studies reporting favourable metabolic effects of TA, the present study shows that after short-term oral therapy there are no significant improvements in glucose tolerance in rodent models of insulin resistance and insulin deficiency. Thioctic acid is unlikely to be of therapeutic benefit as an anti-diabetic drug in clinical practice.
Black
K
K
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Qu
X
X
Seale
J P
JP
Donnelly
R
R
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D005632:Fructose / Q000008:administration & dosage; D005947:Glucose / Q000378:metabolism; D006946:Hyperinsulinism / Q000188:drug therapy / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D000975:Antioxidants; D014280:Triglycerides; D005632:Fructose; D008063:Thioctic Acid; D005947:Glucose