Metabolic Effects of Thioctic Acid in Rodent Models of Insulin Resistance and Diabetes

Abstract

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.

Stimulation of Cardiac Glucose Transport by Thioctic Acid and Insulin

“…Increasing evidence obtained from both experimental studies and investigations in insulin-resistant individuals supports the notion that thioctic acid exerts a beneficial effect on insulin-regulated glucose disposal and may be considered as a new antidiabetic agent 18,19]. However, recently the peripheral effects of thioctic acid on glucose metabolism have been questioned [20]. By using a primary muscle cell with a very high sensitivity towards insulin [9-11], we have now provided additional evidence that thioctic acid is able to completely mimic insulin action on the glucose transport system.…”

Effects of alpha lipoic acid on metabolic syndrome: A comprehensive review

“…According to the information in Table 1, administration of different doses of α‐LA (50 and100 mg/kg, 4–12 weeks) to alloxan‐induced diabetic rats decreased lipid profile and blood glucose (Banji et al, 2011; Thaakur & Lakshmi, 2008). Also, it was observed that administration of α‐LA (10 and 50 mg/kg, 5–10 days) to STZ‐induced diabetic rats decreased fasting blood glucose and exhibited antidiabetic effects (Black et al, 1998; Khamaisi et al, 1999). In another study, oral administration of α‐LA 100 mg/kg for 8 weeks to STZ‐induced diabetes rats reduced HbA1c levels and blood glucose (Budin et al, 2007).…”

Chronic treatment of (R)‐α‐lipoic acid reduces blood glucose and lipid levels in high‐fat diet and low‐dose streptozotocin‐induced metabolic syndrome and type 2 diabetes in Sprague‐Dawley rats

“…), fructose‐fed (Black et al. ), streptozotocin‐induced diabetic rats (Nagamatsu et al. ; Black et al.…”