Isomeric effects of anti-diabetic α-lipoic acid with γ-cyclodextrin

Aims: Previous studies reported the anti-diabetic effects of a-lipoic acid (alpha LA) isomers: racemic-alpha LA, R-alpha LA, or S-alpha LA. Previously, we examined the anti-diabetic effects of alpha LA administered as a food additive, but were unable to demonstrate the differences among different isomers. In this study, alpha LAs were complexed with.-cyclodextrin (gamma CD) for the stability. We then investigated the anti-diabetic effects of racemic-, R-, and S-alpha LA/gamma CDs in KKA(y) mice. Main methods: Male type 2 diabetic KKAy mice were divided into 5 groups, and fed either a high-fat-diet (HFD), HFD supplemented with gamma CD, or HFD supplemented with racemic-alpha LA/gamma CD, R-alpha LA/gamma CD, or S-alpha LA/gamma CD for 4 weeks. At the end of the feeding period, HbA1c and adiponectin levels were measured, PPAR gamma 2 mRNA 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. Key findings: The anti-diabetic effects of alpha LA; the isomeric compounds racemic-, R-, and S-alpha LA/gamma CD were investigated using a male type 2 diabetic KKAy mouse model. Significant differences were observed in HbA1c and plasma adiponectin levels between R-alpha LA/gamma CD-treated mice and control mice. PPAR gamma 2 mRNA expression levels were slightly higher in racemic-and R-alpha LA/gamma CD-treated mice. Moreover, AMPK phosphorylation levels were elevated in racemic-alpha LA/gamma CD- and R-alpha LA/gamma CD-treated mice, but remained unchanged in S-alpha LA/gamma CD-treated mice. Significance: These results suggested that the stereoisomerism mediates a difference in the anti-diabetic effects of racemic-, R-, and S-alpha LA/gamma CDs. Furthermore, the anti-diabetic mechanism of alpha LA/gamma CD action may be attributed to the activation of AMPK in the liver. (C) 2015 Elsevier Inc. All rights reserved.