gamma-cyclodextrin and Diabetes-Mellitus--Type-2

Previous studies reported the anti-diabetic effects of α-lipoic acid (αLA) isomers: racemic-αLA, R-αLA, or S-αLA. Previously, we examined the anti-diabetic effects of αLA administered as a food additive, but were unable to demonstrate the differences among different isomers. In this study, αLAs were complexed with γ-cyclodextrin (γCD) for the stability.We then investigated the anti-diabetic effects of racemic-, R-, and S-αLA/γCDs in KKAy mice.. Male type 2 diabetic KKAy mice were divided into 5 groups, and fed either a high-fat-diet (HFD),HFD supplemented with γCD, or HFD supplemented with racemic-αLA/γCD, R-αLA/γCD, or S-αLA/γCD for 4 weeks. At the end of the feeding period, HbA1c and adiponectin levels were measured, PPARγ2mRNA expression levels were assessed in adipose tissues using real-time PCR, and AMP-activated protein kinase (AMPK) phosphorylation levels were evaluated in the liver by Western blotting.. The anti-diabetic effects of αLA; the isomeric compounds racemic-, R-, and S-αLA/γCD were investigated using amale type 2 diabetic KKAy mousemodel. Significant differences were observed in HbA1c and plasma adiponectin levels between R-αLA/γCD-treated mice and control mice. PPARγ2 mRNA expression levels were slightly higher in racemic- and R-αLA/γCD-treated mice. Moreover, AMPK phosphorylation levels were elevated in racemic-αLA/γCD- and R-αLA/γCD-treated mice, but remained unchanged in S-αLA/γCD-treated mice.. These results suggested that the stereoisomerism mediates a difference in the anti-diabetic effects of racemic-, R-, and S-αLA/γCDs. Furthermore, the anti-diabetic mechanism of αLA/γCD action may be attributed to the activation of AMPK in the liver.

Topics: Adiponectin; Adipose Tissue, White; Animals; Diabetes Mellitus, Type 2; Drug Evaluation, Preclinical; gamma-Cyclodextrins; Gene Expression; Hypoglycemic Agents; Male; Mice; PPAR gamma; Signal Transduction; Stereoisomerism; Thioctic Acid