Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice

Abstract

Aim: To investigate whether alpha-lipoic acid (ALA) could attenuate the insulin resistance and metabolic disorders in high fat diet-fed mice. Methods: Male mice were fed a high fat diet (HFD) plus ALA (100 and 200 mg·kg -1 ·d -1 ) or HFD plus a positive control drug metformin (300 mg·kg ) for 24 weeks. During the treatments, the relevant physiological and metabolic parameters of the mice were measured. After the mice were euthanized, blood samples and livers were collected. The expression of proteins and genes related to glucose metabolism in livers were analyzed by immunoblotting and real time-PCR. Results: HFD induced non-alcoholic fatty liver disease (NAFLD) and abnormal physiological and metabolic parameters in the mice, which were dose-dependently attenuated by ALA. ALA also significantly reduced HFD-induced hyperglycemia and insulin resistance in HFD-fed mice. Furthermore, ALA significantly upregulated the glycolytic enzymes GCK, HK-1 and PK, and the glycogen synthesis enzyme GS, and downregulated the gluconeogenic enzymes PEPCK and G6Pase, thus decreased glucose production, and promoted glycogen synthesis and glucose utilization in livers. Moreover, ALA markedly increased PKB/Akt and GSK3β phosphorylation, and nuclear carbohydrate response element binding protein (ChREBP) expression in livers. Metformin produced similar effects as ALA in HFD-fed mice. Conclusion: ALA is able to sustain glucose homeostasis and prevent the development of NAFLD in HFD-fed mice.

The Flower Tea Coreopsis tinctoria Increases Insulin Sensitivity and Regulates Hepatic Metabolism in Rats Fed a High-Fat Diet

“…Increased gluconeogenesis occurs during substantial hepatic insulin deficiency, thus likely representing the course of type 2 diabetes mellitus (40). Previous results showed that G6Pase and PEPCK, the key gluconeogenic enzymes, were significantly increased in the liver of HFD mice, consistent with our current findings (41,42). As a potential cause of CTregulated hepatic glucose metabolism, the expression levels of G6Pase and PEPCK were significantly decreased upon CT treatment ( Figure 8).…”

The synergistic action of antioxidative enzymes - correlations of catalase and superoxide dismutase in the development and during the treatment of type 2 diabetes

“…The current findings suggest that α-lipoic acid is beneficial and thus should be considered for routine administration in patients with diabetes and peripheral neuropathy [24]. A study by Yang et al [25] demonstrated that metformin might be effective for reducing blood glucose and promoting glucose uptake and utilization and that ALA might be effective for improving insulin sensitivity and activating insulin-signaling pathways. They demonstrated that ALA enhances hepatic insulin sensitivity and prevents the development of Non-alcoholic fatty liver disease, furthermore, ALA ameliorates glucose metabolism by modulating the insulin-signaling pathway.…”

Nε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells

“…ALA also attenuated high-fat diet-induced hyperglycemia and insulin resistance significantly in mice (40). Dietary supplementation of ALA in aged rats was also reported to improve mitochondrial function and reduced oxidative insults in rat models (12).…”