Eddie Vedder
2011-09-24, 08:22
Abstract
Prolonged elevation of plasma free fatty acids (FFAs) induces insulin resistance and impairs pancreatic β-cell adaptation to insulin resistance. The mechanisms whereby lipid induces these impairments are not fully defined, but may involve oxidative stress, inflammation and endoplasmic reticulum stress. α-lipoic acid (ALA), a commonly used health supplement with antioxidant, anti-inflammatory and AMPK-activating properties, has been shown to have therapeutic value in type 2 diabetes and its complications. Here we examined the effects of ALA on insulin sensitivity and secretion in humans under the conditions of 24-h iv lipid infusion to elevate plasma FFAs. Eight overweight and obese male subjects underwent 4 randomized studies each, 4-6 weeks apart: 1) SAL, 2 week oral placebo followed by 24-h iv infusion of saline; 2) IH, 2 week placebo followed by 24-h iv infusion of Intralipid plus heparin to raise plasma FFAs by approximately 2-fold; 3) IH+ALA, 2 week ALA (1800 mg/day) followed by 24-h infusion of Intralipid plus heparin; and 4) ALA, 2 week of ALA followed by 24-h infusion of saline. Insulin secretion rates (ISR) and insulin sensitivity (SI) were assessed with a 2-h, 20-mmol/l hyperglycemic clamp and a hyperinsulinemic-euglycemic clamp, respectively. ISR was not significantly different between treatments. Lipid infusion impaired insulin sensitivity, with and without ALA pre-treatment. These results indicate that ALA, administered orally at this dose for 2 weeks, does not protect against lipid-induced insulin resistance in overweight and obese humans.
http://ajpendo.physiology.org/content/301/4/E736.full
Xiao C, Giacca A, Lewis GF. Short-term oral {alpha}-lipoic acid does not prevent lipid-induced dysregulation of glucose homeostasis in obese and overweight non-diabetic men. Am J Physiol Endocrinol Metab. 2011 Jul 12. [Epub ahead of print]
Prolonged elevation of plasma free fatty acids (FFAs) induces insulin resistance and impairs pancreatic β-cell adaptation to insulin resistance. The mechanisms whereby lipid induces these impairments are not fully defined, but may involve oxidative stress, inflammation and endoplasmic reticulum stress. α-lipoic acid (ALA), a commonly used health supplement with antioxidant, anti-inflammatory and AMPK-activating properties, has been shown to have therapeutic value in type 2 diabetes and its complications. Here we examined the effects of ALA on insulin sensitivity and secretion in humans under the conditions of 24-h iv lipid infusion to elevate plasma FFAs. Eight overweight and obese male subjects underwent 4 randomized studies each, 4-6 weeks apart: 1) SAL, 2 week oral placebo followed by 24-h iv infusion of saline; 2) IH, 2 week placebo followed by 24-h iv infusion of Intralipid plus heparin to raise plasma FFAs by approximately 2-fold; 3) IH+ALA, 2 week ALA (1800 mg/day) followed by 24-h infusion of Intralipid plus heparin; and 4) ALA, 2 week of ALA followed by 24-h infusion of saline. Insulin secretion rates (ISR) and insulin sensitivity (SI) were assessed with a 2-h, 20-mmol/l hyperglycemic clamp and a hyperinsulinemic-euglycemic clamp, respectively. ISR was not significantly different between treatments. Lipid infusion impaired insulin sensitivity, with and without ALA pre-treatment. These results indicate that ALA, administered orally at this dose for 2 weeks, does not protect against lipid-induced insulin resistance in overweight and obese humans.
http://ajpendo.physiology.org/content/301/4/E736.full
Xiao C, Giacca A, Lewis GF. Short-term oral {alpha}-lipoic acid does not prevent lipid-induced dysregulation of glucose homeostasis in obese and overweight non-diabetic men. Am J Physiol Endocrinol Metab. 2011 Jul 12. [Epub ahead of print]