Production and synthesis of a novel 191Pt-labeled platinum complex and evaluation of its biodistribution in healthy mice.

We previously reported that our sugar-conjugated platinum complex (cis-dichloro [(2-fluoro-α-d-glucopylanosidyl) propane-1,3-diamine] platinum: FGC-Pt) has low toxicity and tumor growth inhibitory effect comparable to that of cisplatin. We focused on radioactive Pt isotopes in order to analyze the kinetics of FGC-Pt using gamma-ray imaging techniques, assuming that FGC-Pt could be used for chemotherapy in the future. Therefore, in this study, we aimed to develop a non-invasive method to analyze the biodistribution of FGC-Pt using 191Pt-labeled FGC-Pt ([191Pt]FGC-Pt). 191Pt was produced via the (n,2n) reaction induced by accelerator neutrons. [191Pt]FGC-Pt was prepared using two different methods. In the first method, [191Pt]FGC-Pt (method A) was obtained through the accelerator neutron irradiation of FGC-Pt. In the second method, [191Pt]FGC-Pt (method B) was synthesized using [191Pt]K2PtCl4, which was obtained by the accelerator neutron irradiation of K2PtCl4. Highly purified [191Pt]FGC-Pt was obtained using the latter method, which suggests that the synthetic method using a 191Pt-labeled platinum reagent is suitable for the radioactivation of platinum complexes. We also aimed to investigate whether a significant correlation existed between the biodistribution of FGC-Pt and [191Pt]FGC-Pt in healthy mice 24 h after tail vein administration. FGC-Pt and [191Pt]FGC-Pt were similarly distributed in healthy mice, with a higher accumulation in the liver and kidney 24 h post injection. In addition, a significant correlation (p < 0.05, r = 0.92) between the 191Pt radioactivity concentration (%ID/g (gamma counter)) and platinum concentration (%ID/g (ICP-MS)) was observed in 13 organs. These results suggest that 191Pt-labeled compounds, synthesized using radioactive platinum reagents, can be used to confirm the biodistribution of platinum compounds. Our study on the biodistribution of [191Pt]FGC-Pt is expected to contribute to the development of novel platinum-based drugs in the future.

Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.

Currently, gapmer antisense oligonucleotide (ASO) therapeutics are under clinical development for the treatment of various diseases, including previously intractable human disorders; however, they have the potential to induce hepatotoxicity. Although several groups have reported the reduced hepatotoxicity of gapmer ASOs following chemical modifications of sugar residues or internucleotide linkages, only few studies have described nucleobase modifications to reduce hepatotoxicity. In this study, we introduced single or multiple combinations of 17 nucleobase derivatives, including four novel derivatives, into hepatotoxic locked nucleic acid gapmer ASOs and examined their effects on hepatotoxicity. The results demonstrated successful identification of chemical modifications that strongly reduced the hepatotoxicity of gapmer ASOs. This approach expands the ability to design gapmer ASOs with optimal therapeutic profiles.

Oxygenation saturation index in neonatal hypoxemic respiratory failure.

BACKGROUND: This study aimed to assess the validity of the oxygenation saturation index (OSI) and the ratio of oxygen saturation to the fraction of inspired oxygen (FIO2) (S/F ratio) with percutaneous oxygen saturation (OSISpO2 and the Sp/F ratio) and to evaluate the correlation between these values and the oxygen index (OI). It also determined their cut-off values for predicting OI in accordance with neonatal hypoxic respiratory failure severity. METHODS: We reviewed the data of 77 neonates (gestational age 31.7 ± 6.1 weeks; birthweight, 1768 ± 983 g) requiring invasive mechanical ventilation between 2013 and 2020, 1233 arterial blood gas samples in total. We calculated the OI, OSISpO2, OSI with arterial oxygen saturation (SaO2) (OSISaO2), Sp/F ratio, and the ratio of SaO2 to FIO2 (Sa/F ratio). RESULTS: The regression and Bland-Altman analysis showed good agreement between OSISpO2 or the Sp/F ratio and OSISaO2 or the Sa/F ratio. Although a significant positive correlation was found between OSISpO2 and OI, OSISpO2 was overestimated in SpO2 > 98% with a higher slope of the fitted regression line than that below 98% of SpO2. Furthermore, receiver-operating characteristic curve analysis using only SpO2 ≤ 98% samples showed that the optimal cut-off points of OSISpO2 and the Sp/F ratio for predicting OI were: OI 5, 3.0 and 332; OI 10, 5.3 and 231; OI 15, 7.7 and 108; OI 20, 11.0 and 149; and OI 25, 17.1 and 103, respectively. CONCLUSION: The cut-off OSISpO2 and Sp/F ratio values could allow continuous monitoring for oxygenation changes in neonates with the potential for wider clinical applications.

TogoID: an exploratory ID converter to bridge biological datasets.

MOTIVATION: Understanding life cannot be accomplished without making full use of biological data, which are scattered across databases of diverse categories in life sciences. To connect such data seamlessly, identifier (ID) conversion plays a key role. However, existing ID conversion services have disadvantages, such as covering only a limited range of biological categories of databases, not keeping up with the updates of the original databases and outputs being hard to interpret in the context of biological relations, especially when converting IDs in multiple steps. RESULTS: TogoID is an ID conversion service implementing unique features with an intuitive web interface and an application programming interface (API) for programmatic access. TogoID currently supports 65 datasets covering various biological categories. TogoID users can perform exploratory multistep conversions to find a path among IDs. To guide the interpretation of biological meanings in the conversions, we crafted an ontology that defines the semantics of the dataset relations. AVAILABILITY AND IMPLEMENTATION: The TogoID service is freely available on the TogoID website (https://togoid.dbcls.jp/) and the API is also provided to allow programmatic access. To encourage developers to add new dataset pairs, the system stores the configurations of pairs at the GitHub repository (https://github.com/togoid/togoid-config) and accepts the request of additional pairs. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor.

We have successfully synthesized piperidine and pyrrolidine derivatives by electroreductive cyclization using readily available imine and terminal dihaloalkanes in a flow microreactor. Reduction of the substrate imine on the cathode proceeded efficiently due to the large specific surface area of the microreactor. This method provided target compounds in good yields compared to a conventional batch-type reaction. Furthermore, piperidine and pyrrolidine derivatives could be obtained on preparative scale by continuous electrolysis for approximately 1 hour.

Technical considerations in Hi-C scaffolding and evaluation of chromosome-scale genome assemblies.

The recent development of ecological studies has been fueled by the introduction of massive information based on chromosome-scale genome sequences, even for species for which genetic linkage is not accessible. This was enabled mainly by the application of Hi-C, a method for genome-wide chromosome conformation capture that was originally developed for investigating the long-range interaction of chromatins. Performing genomic scaffolding using Hi-C data is highly resource-demanding and employs elaborate laboratory steps for sample preparation. It starts with building a primary genome sequence assembly as an input, which is followed by computation for genome scaffolding using Hi-C data, requiring careful validation. This article presents technical considerations for obtaining optimal Hi-C scaffolding results and provides a test case of its application to a reptile species, the Madagascar ground gecko (Paroedura picta). Among the metrics that are frequently used for evaluating scaffolding results, we investigate the validity of the completeness assessment of chromosome-scale genome assemblies using single-copy reference orthologues.

Integrated Flow Synthesis of α-Amino Acids by In Situ Generation of Aldimines and Subsequent Electrochemical Carboxylation.

The synthesis of α-amino acids was carried out in a continuous flow system. In this system, aldimines were efficiently generated in situ via the dehydration-condensation of aldehydes with anilines in a desiccant bed column filled with 4 Å molecular sieves desiccant, followed by reaction with CO2 in an electrochemical flow microreactor to afford the α-amino acids in high to moderate yields. The present system can provide α-amino acids without using stoichiometric amounts of metal reagents or highly toxic cyanide reagents.

Reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates with respiratory distress.

Hypercapnia occurs in ventilated infants even if tidal volume (VT) and minute ventilation (VE) are maintained. We hypothesised that increased physiological dead space (Vd,phys) caused decreased minute alveolar ventilation (VA; alveolar ventilation (VA) × respiratory rate) in well-ventilated infants with hypercapnia. We investigated the relationship between dead space and partial pressure of carbon dioxide (PaCO2) and assessed VA. Intubated infants (n = 33; mean birth weight, 2257 ± 641 g; mean gestational age, 35.0 ± 3.3 weeks) were enrolled. We performed volumetric capnography (Vcap), and calculated Vd,phys and VA when arterial blood sampling was necessary. PaCO2 was positively correlated with alveolar dead space (Vd,alv) (r = 0.54, p < 0.001) and Vd,phys (r = 0.48, p < 0.001), but not Fowler dead space (r = 0.14, p = 0.12). Normocapnia (82 measurements; 35 mmHg ≤ PaCO2 < 45 mmHg) and hypercapnia groups (57 measurements; 45 mmHg ≤ PaCO2) were classified. The hypercapnia group had higher Vd,phys (median 0.57 (IQR, 0.44-0.67)) than the normocapnia group (median Vd,phys/VT = 0.46 (IQR, 0.37-0.58)], with no difference in VT. The hypercapnia group had lower VA (123 (IQR, 87-166) ml/kg/min) than the normocapnia group (151 (IQR, 115-180) ml/kg/min), with no difference in VE.Conclusion: Reduction of VA in well-ventilated neonates induces hypercapnia, caused by an increase in Vd,phys. What is Known: • Volumetric capnography based on ventilator graphics and capnograms is a useful tool in determining physiological dead space of ventilated infants and investigating the cause of hypercapnia. What is New: • This study adds evidence that reduction in minute alveolar ventilation causes hypercapnia in ventilated neonates.

Evaluation of off-target effects of gapmer antisense oligonucleotides using human cells.

Antisense oligonucleotide (ASO) has the potential to induce off-target effects due to complementary binding between the ASO and unintended RNA with a sequence similar to the target RNA. Conventional animal studies cannot be used to assess toxicity induced by off-target effects because of differences in the genome sequence between humans and other animals. Consequently, the assessment of off-target effects with in silico analysis using a human RNA database and/or in vitro expression analysis using human cells has been proposed. Our previous study showed that the number of complementary regions of ASOs with mismatches in the human RNA sequences increases dramatically as the number of tolerated mismatches increases. However, to what extent the expression of genes with mismatches is affected by off-target effects at the cellular level is not clear. In this study, we evaluated off-target effects of gapmer ASOs, which cleave the target RNA in an RNase H-dependent manner, by introducing the ASO into human cells and performing microarray analysis. Our data indicate that gapmer ASOs induce off-target effects depending on the degree of complementarity between the ASO and off-target candidate genes. Based on our results, we also propose a scheme for the assessment of off-target effects of gapmer ASOs.

Bright and dark sides of exercise effects on biological responses such as energy metabolism and renal function in rats with renal failure and fructose-induced glucose intolerance.

In the present study, we investigated the beneficial and risky effects of exercise intended to prevent or treat lifestyle-related diseases on insulin sensitivity, lactic acid utilization, lipid metabolism, hepatic and renal oxidative stress, hepatic selenoprotein P and renal function in obese and glucose-intolerant rats with renal failure. We fed normal rats a 20% casein diet while the glucose-intolerant, obese rats received a high-fructose diet, and after then rats received single injection of vancomycin at a dose of 400 mg/kg for constructing the duplicative state of renal failure and diabetes mellitus. They were forced to run for 1 h/day, 6 days/week, for 10 weeks. Exercise reduced visceral fat and ameliorated insulin sensitivity in the high-fructose group, improved lactic acid usage efficiency, however, increased hepatic oxidative stress and complicated renal dysfunction in the normal and high-fructose fed groups with renal failure. Additionally, exercise upregulated hepatic selenoprotein P expression and enhanced renal antioxidative system in both groups. It is concluded that strictly controlled exercise conditions must be adapted to patient health states especially in view of kidney protection, and supplemental therapy is also recommended in parallel with exercise, using nutrients and vitamins for kidney protection.

Effects of exercise on biological trace element concentrations and selenoprotein P expression in rats with fructose-induced glucose intolerance.

In the present study, we investigated the effects of exercise intended to prevent or treat lifestyle-related diseases on the glucose tolerance, insulin level, lactic acid utilization, muscle glycogen synthesis, hepatic and renal oxidative stress, hepatic selenoprotein P and biological trace element levels in organs of obese, glucose-intolerant rats. We fed normal, healthy rats a 20% casein diet while the glucose-intolerant, obese rats received a high-fructose diet. They were forced to run for one hour per day, six days per week, for ten weeks. Exercise reduced visceral fat and ameliorated glucose tolerance in the high-fructose group, lowered blood lactic acid levels, improved lactic acid usage efficiency, and increased oxidative stress and hepatic levels of Mn, Fe, Cu, and Zn in the normal and high-fructose groups. Additionally, exercise significantly upregulated hepatic selenoprotein P expression in both groups, however, its effect was remarkable in healthy group. On the other hand, muscle glycogen synthesis was not markedly enhanced in high-fructose-diet rats but in normal-diet rats in response to exercise. It is concluded that exercise conditions rather than exercise load must be customized and optimized for each health and disease states in advance before starting exercise training intended to prevent or treat lifestyle-related diseases.

Estimated number of off-target candidate sites for antisense oligonucleotides in human mRNA sequences.

Antisense oligonucleotide (ASO) therapeutics are single-stranded oligonucleotides which bind to RNA through sequence-specific Watson-Crick base pairings. A unique mechanism of toxicity for ASOs is hybridization-dependent off-target effects that can potentially occur due to the binding of ASOs to complementary regions of unintended RNAs. To reduce the off-target effects of ASOs, it would be useful to know the approximate number of complementary regions of ASOs, or off-target candidate sites of ASOs, of a given oligonucleotide length and complementarity with their target RNAs. However, the theoretical number of complementary regions with mismatches has not been reported to date. In this study, we estimated the general number of complementary regions of ASOs with mismatches in human mRNA sequences by mathematical calculation and in silico analysis using several thousand hypothetical ASOs. By comparing the theoretical number of complementary regions estimated by mathematical calculation to the actual number obtained by in silico analysis, we found that the number of complementary regions of ASOs could be broadly estimated by the theoretical number calculated mathematically. Our analysis showed that the number of complementary regions increases dramatically as the number of tolerated mismatches increases, highlighting the need for expression analysis of such genes to assess the safety of ASOs.

Pituitary apoplexy after cardiac surgery in a 14-year-old girl with Carney complex: a case report.

A 14-year-old girl was referred to our department because of headache and visual impairment following the resection of recurrent cardiac myxoma. Head magnetic resonance imaging (MRI) scan detected an intra- and supra-sellar tumor. Moreover, the patient showed the presence of spotty skin pigmentations on her cheeks and lower lip. Blood examination revealed hypothyrotropinemia, and ultrasonography results revealed multiple thyroid nodules. She was diagnosed with Carney complex (CNC). Her pituitary tumor was suspected as growth hormone (GH)-secreting adenoma, because overgrowth was observed in the patient. However, biochemical examinations, including oral glucose tolerance test, failed to show the characteristic findings of GH-secreting adenoma. In contrast, insulin tolerance test showed GH deficiency. Her visual impairment improved without performing decompression surgery, and the tumor size decreased, as per the MRI findings. Based on clinical course, the patient was diagnosed with pituitary apoplexy in pituitary adenoma, following which she was discharged. At 3 months after discharge, thyrotropin-releasing hormone loading test performed revealed low thyrotropin-stimulating hormone and thyroid hormone levels, and the patient was in a depressed mood. Therefore, l-T4 replacement was initiated, following which her GH secretory capacity gradually improved. Here, we report, to the best of our knowledge, the first case of a patient with pituitary apoplexy in CNC. Such condition must be identified in young patients with recurrent cardiac myxoma, and examinations, such as head MRI, must be performed.

Competing Interactions in Hierarchical Porphyrin Self-Assembly Introduce Robustness in Pathway Complexity.

Pathway complexity in supramolecular polymerization has recently sparked interest as a method to generate complex material behavior. The response of these systems relies on the existence of a metastable, kinetically trapped state. In this work, we show that strong switch-like behavior in supramolecular polymers can also be achieved through the introduction of competing aggregation pathways. This behavior is illustrated with the supramolecular polymerization of a porphyrin-based monomer at various concentrations, solvent compositions, and temperatures. It is found that the monomers aggregate via an isodesmic mechanism in weakly coupled J-type aggregates at intermediate solvent quality and temperature, followed by nucleated H-aggregates at lower solvent qualities and temperatures. At further increased thermodynamic driving forces, such as high concentration and low temperature, the H-aggregates can form hierarchical superhelices. Our mathematical models show that, contrary to a single-pathway polymerization, the existence of the isodesmic aggregation pathway buffers the free monomer pool and renders the nucleation of the H-aggregates insensitive to concentration changes in the limit of high concentrations. We also show that, at a given temperature or solvent quality, the thermodynamically stable aggregate morphology can be selected by controlling the remaining free external parameter. As a result, the judicious application of pathway complexity allows us to synthesize a diverse set of materials from only a single monomer. We envision that the engineering of competing pathways can increase the robustness in a wide variety of supramolecular polymer materials and lead to increasingly versatile applications.

Anti-hyperglycemic Effect of Long-Term Bis(hinokitiolato)zinc Complex ([Zn(hkt)2]) Ingestion on Insulin Resistance and Pancreatic Islet Cells Protection in Type 2 Diabetic KK-Ay Mice.

Zinc (Zn) is a trace element with anti-diabetes mellitus (anti-DM) effects. Zn complexes exhibit stronger insulin-like activity than Zn ions. Bis(hinokitiolato)zinc complex ([Zn(hkt)2]) was recently reported to be a potent anti-DM candidate. We examined the effects of [Zn(hkt)2] on insulin resistance and pancreatic islet cells through in vivo long-term ingestion studies. In an in vivo study, we performed 4-month long-term [Zn(hkt)2] administration experiments in KK-Ay mice as a type 2 DM animal model. Ingestion of [Zn(hkt)2] resulted in lower blood glucose levels compared with the non-treated KK-Ay mice (control group). Additionally, [Zn(hkt)2] treatment decreased plasma insulin concentration compared with that of the non-treated KK-Ay group. [Zn(hkt)2] treatment resulted in a significant suppression of islet cell enlargement and a significantly decreased number of insulin-positive cells compared with the non-treated KK-Ay control group. The [Zn(hkt)2] treatment group showed the increasing tendency in the amount of Zn levels in peripheral organs; liver, muscle, adipose, and pancreas, compared with the non-treated KK-Ay control group. However, the Zn level in the pancreas of the [Zn(hkt)2] treatment group did not show the significant increase compared with the non-treated KK-Ay control group. This accumulation of Zn in pancreas suggested that [Zn(hkt)2] mainly effects on the peripheral tissue, and [Zn(hkt)2] has the less effect on the pancreas directly. Thus, we concluded that [Zn(hkt)2] exerted the main effect on peripheral organs by ameliorating insulin resistance.

CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites.

UNLABELLED: CRISPRdirect is a simple and functional web server for selecting rational CRISPR/Cas targets from an input sequence. The CRISPR/Cas system is a promising technique for genome engineering which allows target-specific cleavage of genomic DNA guided by Cas9 nuclease in complex with a guide RNA (gRNA), that complementarily binds to a ∼ 20 nt targeted sequence. The target sequence requirements are twofold. First, the 5'-NGG protospacer adjacent motif (PAM) sequence must be located adjacent to the target sequence. Second, the target sequence should be specific within the entire genome in order to avoid off-target editing. CRISPRdirect enables users to easily select rational target sequences with minimized off-target sites by performing exhaustive searches against genomic sequences. The server currently incorporates the genomic sequences of human, mouse, rat, marmoset, pig, chicken, frog, zebrafish, Ciona, fruit fly, silkworm, Caenorhabditis elegans, Arabidopsis, rice, Sorghum and budding yeast. AVAILABILITY: Freely available at http://crispr.dbcls.jp/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bis(hinokitiolato)zinc complex ([Zn(hkt)2]) activates Akt/protein kinase B independent of insulin signal transduction.

Since many Zn complexes have been developed to enhance the insulin-like activity and increase the exposure and residence of Zn in the animal body, these complexes are recognized as one of the new candidates with action mechanism different from existing anti-diabetic drugs. However, the molecular mechanism by which Zn complexes exert an anti-DM effect is unknown. Therefore, we evaluated the activity of Zn complexes, especially related to the phosphorylation of insulin signaling pathway components. We focused on the insulin-like effects of the bis(hinokitiolato)zinc complex, [Zn(hkt)2], using 3T3-L1 adipocytes. [Zn(hkt)2] was taken up by cells and induced Akt phosphorylation in a time-dependent manner. Additionally, it showed inhibitory activity against PTP1B and PTEN, which are major negative regulators of insulin signaling. It did not promote the phosphorylation of IR (insulin receptor)-ß or IRS (insulin receptor substrate)-1 by itself, but in combination with insulin, it enhanced the phosphorylation of IRß. We conclude that [Zn(hkt)2] has effects on the proteins of insulin signaling pathway without insulin receptor mediation, and [Zn(hkt)2] promotes insulin function and shows the anti-DM effects. Thus, [Zn(hkt)2] may be the basis for improved DM treatments.

Intercontinental dispersal of HIV-1 subtype B associated with transmission among men who have sex with men in Japan.

UNLABELLED: Transmission clusters of HIV-1 subtype B uniquely associated with the epidemic among men who have sex with men (MSM) in East Asia have recently been identified. Using the Los Alamos HIV sequence database and the UK HIV drug resistance database, we explored possible links between HIV MSM epidemics in East Asia and the rest of the world by using phylogenetic and molecular clock analyses. We found that JP.MSM.B-1, a subtype B MSM variant that accounts for approximately one-third of the infections among Japanese MSM, was detected worldwide, in the United Kingdom (n=13), mainland China (n=3), the United States, Germany, Canada, and Taiwan (n=1 each). Interestingly, 10 United Kingdom samples plus two from Germany and the United States formed a distinct monophyletic subgroup within JP.MSM.B-1. The estimated divergence times of JP.MSM.B-1 and the latter subgroup were ∼1989 and ∼1999, respectively. These dates suggest that JP.MSM.B-1 was circulating for many years in Japan among MSM before disseminating to other countries, most likely through global MSM networks. A significant number of other Asian MSM HIV lineages were also detected in the UK HIV drug resistance database. Our study provides insight into the regional and global dispersal of Asian MSM HIV lineages. Further study of these strains is warranted to elucidate viral migration and the interrelationship of HIV epidemics on a global scale. IMPORTANCE: We previously identified several transmission clusters of HIV-1 subtype B uniquely associated with the epidemic among men who have sex with men (MSM) in East Asia. Using the Los Alamos HIV sequence database and the UK HIV drug resistance database, we explored the possible interplay of HIV MSM epidemics in the different geographic regions and found previously unrecognized interrelationships among the HIV-1 epidemics in East Asia, the United Kingdom, and the rest of the world. Our study provides insight into the regional and global dispersal of Asian MSM HIV lineages and highlights the importance of strengthening HIV monitoring efforts and the need for implementing effective control measures to reduce HIV transmission on a global scale.

GGRNA: an ultrafast, transcript-oriented search engine for genes and transcripts.

GGRNA (http://GGRNA.dbcls.jp/) is a Google-like, ultrafast search engine for genes and transcripts. The web server accepts arbitrary words and phrases, such as gene names, IDs, gene descriptions, annotations of gene and even nucleotide/amino acid sequences through one simple search box, and quickly returns relevant RefSeq transcripts. A typical search takes just a few seconds, which dramatically enhances the usability of routine searching. In particular, GGRNA can search sequences as short as 10 nt or 4 amino acids, which cannot be handled easily by popular sequence analysis tools. Nucleotide sequences can be searched allowing up to three mismatches, or the query sequences may contain degenerate nucleotide codes (e.g. N, R, Y, S). Furthermore, Gene Ontology annotations, Enzyme Commission numbers and probe sequences of catalog microarrays are also incorporated into GGRNA, which may help users to conduct searches by various types of keywords. GGRNA web server will provide a simple and powerful interface for finding genes and transcripts for a wide range of users. All services at GGRNA are provided free of charge to all users.

Antidiabetic effect of the α-lipoic acid γ-cyclodextrin complex.

In recent years, the number of patients suffering from diabetes mellitus has been increasing worldwide. In particular, type 2 diabetes mellitus, a lifestyle-related disease, is recognized as a serious disease with various complications. Many types of pharmaceutics or specific health foods have been used for the management of diabetes mellitus. At the same time, the relationship between diabetes mellitus and α-lipoic acid has been recognized for many years. In this study, we found that the α-lipoic acid γ-cyclodextrin complex exhibited an HbA1c lowering effect for treating type 2 diabetes mellitus in animal models. Moreover, in this study, we investigated the activation of phosphorylation of AMP-activated protein kinase, which plays a role in cellular energy homeostasis, in the liver of KKA(y) mice by using α-lipoic acid and the α-lipoic acid γ-cyclodextrin complex. Our results show that the α-lipoic acid γ-cyclodextrin complex strongly induced the phosphorylation of AMP-activated protein kinase. Thus, we concluded that intake of the α-lipoic acid γ-cyclodextrin complex exerted an antidiabetic effect by suppressing the elevation of postprandial hyperglycemia as well as doing exercise.