title: Isomeric effects of anti-diabetic α-lipoic acid with γ-cyclodextrin.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Naito
authors.affiliation: Department of Social/Community Medicine and Health Science, Food and Drug Evaluation Science, Kobe University Graduate School of Medicine, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ikuta
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Okano
authors.affiliation: CycloChem Bio Co., Ltd., Kobe, Japan.
authors.forename: Hinako
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: CycloChem Bio Co., Ltd., Kobe, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakata
authors.affiliation: CycloChem Bio Co., Ltd., Kobe, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.affiliation: Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women's University, Japan.
authors.forename: Kinuyo
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women's University, Japan.
authors.forename: Naemi
authors.initials: N
authors.lastname: Kajiwara
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, Japan; Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women's University, Japan. Electronic address: y-yoshikawa@yg.kobe-wu.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
mesh_terms: D052242:Adiponectin / Q000097:blood; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000494:pharmacology*; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D047408:gamma-Cyclodextrins; D008063:Thioctic Acid; C023792:gamma-cyclodextrin
keywords: AMP-activated protein kinase; Anti-diabetic effect; High fat diet (HFD); Peroxisome proliferator-activated receptor (PPAR); R-α-lipoic acid/γ-cyclodextrin (γCD) complex