Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin

Fujii K., Fujishima Y., Kita S., et al. Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin. Scientific Reports 14, 3620 (2024); https://doi.org/10.1038/s41598-024-51935-6.Pharmacological activation of hypoxia-inducible factor 1 (HIF-1), a hypoxia-responsive transcription factor, has attracted increasing attention due to its efficacy not only in renal anemia but also in various disease models. Our study demonstrated that a HIF-1 activator enhanced extracellular vesicle (EV) production from cultured endothelial cells synergistically with adiponectin, an adipocyte-derived factor, through both transcriptional induction and posttranscriptional stabilization of an adiponectin binding partner, T-cadherin. Increased EV levels were observed in wild-type mice but not in T-cadherin null mice after consecutive administration of roxadustat. Adiponectin- and T-cadherin-dependent increased EV production may be involved in the pleiotropic effects of HIF-1 activators

Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment

Yusuke Kawachi; Yuya Fujishima; Hitoshi Nishizawa; Hirofumi Nagao; Takashi Nakamura; Seigo Akari; Takayo Murase; Naohiro Taya; Kazuo Omori; Akimitsu Miyake; Shiro Fukuda; Mitsuyoshi Takahara; Shunbun Kita; Naoto Katakami; Norikazu Maeda; Iichiro Shimomura. Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment. J Diabetes Investig. 2020

Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling

Okita T., Kita S., Fukuda S., et al. Soluble T-cadherin secretion from endothelial cells is regulated via insulin/PI3K/Akt signalling. Biochemical and Biophysical Research Communications 732, 150403 (2024); https://doi.org/10.1016/j.bbrc.2024.150403.Aim and objective: Our recent report showed that soluble T-cadherin promotes pancreatic beta-cell proliferation. However, how and where the secretion of soluble T-cadherin is regulated remain unclear. Methods and results: Soluble T-cadherin levels significantly increased in leptin receptor-deficient db/db mice with hypoinsulinaemia or in wild-type mice treated with insulin receptor blockade by S961. Similar results were observed in human subjects; Diabetic ketoacidosis patients at the time of hospitalization had increased plasma soluble T-cadherin levels, which decreased after insulin infusion therapy. Patients with recurrent ovarian cancer who were administered a phosphatidylinositol-3 kinase (PI3K)-alpha inhibitor (a new anticancer drug) had increased plasma soluble T-cadherin and plasma C-peptide levels. Endothelial cell-specific T-cadherin knockout mice, but not skeletal muscle- or cardiac muscle-specific T-cadherin knockout mice, showed a 26 % reduction in plasma soluble T-cadherin levels and a significant increase in blood glucose levels in streptozocin-induced diabetes. The secretion of soluble T-cadherin from human endothelial cells was approximately 20 % decreased by insulin and this decrease was canceled by blockade of insulin receptor/Akt signalling, not Erk signalling. Conclusion: We conclude that insulin regulates soluble T-cadherin levels and soluble T-cadherin secretion from endothelial cells is positively regulated by insulin/insulin receptor/Akt signalling

Feasibility pilot study of a Japanese teaching kitchen program

BackgroundThis pilot study examined the feasibility of a new lifestyle modification program involving a “Teaching Kitchen” in Japan. Our goal was to explore (1) feasibility of the program; (2) acceptability for class frequency (weekly vs. bi-weekly); and (3) changes in biometrics, dietary intakes, and lifestyle factors.MethodsA total of 24 employees with obesity in a Japanese company were recruited. Participants were randomly divided into two groups (weekly or bi-weekly group), each attending the program consisting of four two-hour classes (lectures on nutrition, exercise, mindfulness, and culinary instructions). Participants were observed for changes in dietary intakes, biometrics, and health related quality of life over the subsequent 3 months. We tested the between-group differences in changes using linear mixed-effect models.ResultsThe program completion rates were 83.3% in total (91.7% for weekly group and 75.0% for bi-weekly group). From baseline to post-intervention, significant decreases were observed in weight (p < 0.001), body mass index (p < 0.001), diastolic blood pressure (p = 0.03), body fat mass (p < 0.001), and dietary intakes in total fat (p = 0.03) and sodium (p = 0.008) among 17 participants who were available for measurements. Improvements in biometrics remained significant 1 month after the intervention (all p ≤ 0.03 in 14 participants). Participants' health related quality of life was significantly improved in bodily pain, general health, vitality, and mental component score (all p ≤ 0.047).ConclusionsThe new Japanese Teaching Kitchen program is feasible with high program completion rates in Japanese office workers with obesity. While this was a small feasibility study, significant multiple improvements in dietary intakes, biometrics, and health related quality of life suggest that this line of inquiry warrants further exploration to address obesity and obesity-related diseases in Japan

Correlation between plasma glutamate and adiponectin in patients with type 2 diabetes

Nagao H., Nishizawa H., Fukuda S., et al. Correlation between plasma glutamate and adiponectin in patients with type 2 diabetes. Endocrine Journal 71, 55 (2024); https://doi.org/10.1507/endocrj.EJ23-0506.Visceral fat accumulation is a major determinant of type 2 diabetes mellitus and cardiovascular diseases. Recent studies have reported that glutamate is the most elevated amino acid in the plasma amino acid profile in patients with obesity and/or visceral fat accumulation. Here, we show the relationship between plasma glutamate and the clinical features of patients with type 2 diabetes. The study subjects were 62 (28 men and 34 women) Japanese patients with type 2 diabetes. Blood profiles, including glutamate and adiponectin (APN) levels and estimated visceral fat area (eVFA), were measured. We also evaluated the plasma amino acid levels in mice with or without obesity by GC/MS analysis. In patients with type 2 diabetes, plasma glutamate was positively correlated with BMI, eVFA, and fasting insulin but negatively correlated with APN and duration of diabetes. Additionally, multiple regression analysis revealed that plasma glutamate was a significant determinant of APN. The plasma glutamate level was most significantly increased in obese mice compared to control mice, and it was negatively correlated with APN. These results suggest that the level of plasma glutamate could be a strong indicator of adipocyte dysfunction in patients with type 2 diabetes

Correlation between plasma glutamate and adiponectin in patients with type 2 diabetes

Visceral fat accumulation is a major determinant of type 2 diabetes mellitus and cardiovascular diseases. Recent studies have reported that glutamate is the most elevated amino acid in the plasma amino acid profile in patients with obesity and/or visceral fat accumulation. Here, we show the relationship between plasma glutamate and the clinical features of patients with type 2 diabetes. The study subjects were 62 (28 men and 34 women) Japanese patients with type 2 diabetes. Blood profiles, including glutamate and adiponectin (APN) levels and estimated visceral fat area (eVFA), were measured. We also evaluated the plasma amino acid levels in mice with or without obesity by GC/MS analysis. In patients with type 2 diabetes, plasma glutamate was positively correlated with BMI, eVFA, and fasting insulin but negatively correlated with APN and duration of diabetes. Additionally, multiple regression analysis revealed that plasma glutamate was a significant determinant of APN. The plasma glutamate level was most significantly increased in obese mice compared to control mice, and it was negatively correlated with APN. These results suggest that the level of plasma glutamate could be a strong indicator of adipocyte dysfunction in patients with type 2 diabetes

Influence of Reinforcing Rebar on Expansion due to Delayed Ettringite Formation along the Bonding Length – Part II: Bond Performance of Reinforced Concrete Affected by DEF Expansion

International audienceThe purpose of this study is to clarify the bond behavior between rebar and concrete during DEF expansion and pullout testing. The details of the expansion test and the influence of reinforcing bar on DEF expansion have been precisely described in Part I. In Part II, the data related to the bond test is described. The change in bond behavior due to DEF expansion is investigated via the one-end pullout test and the influence of DEF expansion on the bond behavior is discussed. The local bond behavior (slip and bond stress) during the pullout test of the specimens without stirrups is observed to be dramatically changed by DEF expansion. Regarding the specimens with stirrups, failure did not occur during the pullout test and the local bond behavior slightly changed as in the case without stirrups. From the experimental results, a conceptual diagram is proposed to explain the bond behavior during DEF expansion and the pullout test based on the general conceptual understanding of the bond. It can be considered that the direction of local slip and local bond stress during the pullout test is opposite to that during the expansion process. This results in the observed complex local bond behavior during DEF expansion and the pullout test and the effect of stirrups on DEF expansion

Influence of Reinforcing Rebar on Expansion due to Delayed Ettringite Formation along the Bonding Length – Part I: The Role of Bond on Expansive Behavior of Concrete

International audienceThis paper explores the effects of rebar as an internal restraint on the expansion of delayed ettringite formation (DEF) in concrete. Concrete specimens embedded with steel bars without end plates are subjected to heat treatment followed by immersion in water. The effect of stirrups on expansion is also investigated. The results show that the longitudinal expansion of specimens without stirrups differs depending on the longitudinal position, owing to the different degrees of restraint resulting from stress in the steel bar. The final transverse expansions of the specimens without stirrups are close to those measured for stress-free specimens. Conversely, longitudinal and transverse expansions are significantly reduced in the specimens with stirrups. This indicates that the combination of a longitudinal steel bar and stirrups induces three-dimensional confinement stresses that help to limit DEF expansion in both the longitudinal and transverse directions. Furthermore, possible debonding along the longitudinal bar is observed in specimens without stirrups when the transverse expansion of the prismatic specimens is 0.4 to 0.6%. This behavior is not observed in the specimens with stirrups, which demonstrates the effectiveness of three-dimensional restraints in significantly mitigating the risk of debonding, as well as DEF expansion