Role of Epac2A/Rap1 Signaling in Interplay Between Incretin and Sulfonylurea in Insulin Secretion

Takahashi, Harumi,Shibasaki, Tadao,Park, Jae-Hyung,Hidaka, Shihomi,Takahashi, Toshimasa,Ono, Aika,Song, Dae-Kyu,Seino, Susumu American Diabetes Association 2015 Diabetes Vol.64 No.4

<P>Incretin-related drugs and sulfonylureas are currently used worldwide for the treatment of type 2 diabetes. We recently found that Epac2A, a cAMP binding protein having guanine nucleotide exchange activity toward Rap, is a target of both incretin and sulfonylurea. This suggests the possibility of interplay between incretin and sulfonylurea through Epac2A/Rap1 signaling in insulin secretion. In this study, we examined the combinatorial effects of incretin and various sulfonylureas on insulin secretion and activation of Epac2A/Rap1 signaling. A strong augmentation of insulin secretion by combination of GLP-1 and glibenclamide or glimepiride, which was found in <I>Epac2A</I><SUP>+/+</SUP> mice, was markedly reduced in <I>Epac2A</I><SUP>−/−</SUP> mice. In contrast, the combinatorial effect of GLP-1 and gliclazide was rather mild, and the effect was not altered by Epac2A ablation. Activation of Rap1 was enhanced by the combination of an Epac-selective cAMP analog with glibenclamide or glimepiride but not gliclazide. In diet-induced obese mice, ablation of Epac2A reduced the insulin secretory response to coadministration of the GLP-1 receptor agonist liraglutide and glimepiride. These findings clarify the critical role of Epac2A/Rap1 signaling in the augmenting effect of incretin and sulfonylurea on insulin secretion and provide the basis for the effects of combination therapies of incretin-related drugs and sulfonylureas.</P>

Arteriovenous Fistula at the Craniocervical Junction Found After Cervical Laminoplasty for Ossification of the Posterior Longitudinal Ligament

Susumu Sasada,Masafumi Hiramatsu,Akira Ksumegi,Haruto Fujimura,Shogo Oshikata,Yuichi Takahashi,Kenki Nishida,Takao Yasuhara,Isao Date 대한척추신경외과학회 2020 Neurospine Vol.17 No.4

Ossification of the posterior longitudinal ligament (OPLL) is common in East Asia. Arteriovenous fistula at the craniocervical junction (CCJ-AVF), in contrast, is rare. As OPLL occurs most often in the cervical region, these 2 conditions can coexist in the cervical spinal canal of a single patient. We report a case of CCJ-AVF found after cervical laminoplasty (CLP) for OPLL. A 68-year-old man experienced progressive myelopathy due to cervical OPLL. Magnetic resonance imaging (MRI) revealed a high-intensity area inside the spinal cord. CLP was performed and his symptoms immediately improved. Three months after CLP, however, myelopathy recurred. MRI revealed an exacerbated and enlarged high-intensity area inside the cord from the medulla oblongata to the C4/5 level with a flow void around the cord. Left vertebral artery angiography revealed CCJ-AVF with ascending and descending draining veins. Direct surgery was performed to interrupt shunt flow into the draining veins. The patient’s symptoms improved to a limited degree. In this case, increased pressure inside the spinal canal due to OPLL might have decreased the shunt flow of the CCJ-AVF. Thus, the venous congestion induced by CCJ-AVF might have been exacerbated after the pressure was removed by CLP. Magnetic resonance angiography screening could help detect concurrent CCJ-AVF and OPLL.

이퇴계 「경(敬)」 사상の 윤리학적 고찰

고교진 퇴계학연구원 1987 退溪學報 Vol.54 No.1

동아시아에 있어서의 『경(敬)』 철학의 성립과 전개

고교진 퇴계학연구원 1984 退溪學報 Vol.44 No.1

『聖學十圖』의 思想體系

高橋進 단국대학교 퇴계학연구소 1987 退溪學硏究 Vol.1 No.-

이퇴계의 인간관(제1부)

고교진 퇴계학연구원 1983 退溪學報 Vol.39 No.1

The problems of the acceptance by Yi T'oegye of the philosophy of Chu Hsi(朱熹), and Neo-Confucianism, in the Sung (宋) era, and the nature of the philosophy he himself established are closely connected with the development of Chu Hsi's philosophy in East Asia and its historical features. From this perspective, I attempt in this paper to investigate Yi T'oegye's thoughts in the Cheonmyeongtoseol (天命圖說), which engendered a famous controversy concerning the Four Beginnings-Seven Emotions Thesis (四端七情論) between Yi T'oegye and Ki Kobong (奇高峰). Yi T'oegye's view of human being, especially his theory of the interrelation between heaven and man found in the Cheonmyeongtoseol, which he himself established consequent upon his acceptance of traditional Confucianism and Neo-Confucianism in the Sung era, remains an important point in his philosophy. Firstly, he asserted that $quot;Heaven has the identity of Ultimate Principle$quot; (天卽理, cheon jeuk ri). ana recognized the functions of won, hyon, ri, and jeong (元亭利貞) both as the four virtues (四德, sa deong) and the four fundamental principles (四理, sa ri). Further, his elaborate theories specified the relationships between the four virtues-four fundamental principles, the functions of ki (氣), eum (陰), and yang (陽), and the five elements(五行 o haeng). Thus, secondly, he clearly explained the derivation of all things and affairs (all phenomenal existence) through his rational theory of i and ki. Consequently, although he retained the concept of the $quot;Mandate of Heaven$quot; (天命) as a mere word, its literal meaning, as the functions of Heaven, appeared to become rare or extinct. This was a typical argument, and may be contrusted with Chu Hsi's logic of T'ien-ming (天命), which is commented on in the first phrase of the Doctrine of the Mean (中庸). Thirdly, Yi T'oegye indubitably imported dynamic characteristics to i and original human nature. Thus he argued that i, in the human mind, had four virtues, and established the five basic virtues (五常) and the four innate moral senses (the so called Four Beginnings), which he called original human nature, and ki, in human mind, formed the nature of physical despositions or material nature, from which arose the seven emotions. In this logical process, he argued that $quot;the names of human nature or emotion are identical, but their functions appear in various ways.$quot; Thus, the controversy between Yi T'oegye and Ki Kobong arose from the theory of nature and emotion in human being. This lead Yi T'oegye to formulate his specific theories of practice.

퇴계철학의 체계적 구성 「성학십도(聖學十圖)」 를 기초로

고교진,이재희 퇴계학연구원 1983 退溪學報 Vol.40 No.1

세계사상사における퇴계학 - 「경(敬)」 の 철학とカソト윤리학 -

고교진 퇴계학연구원 1986 退溪學報 Vol.52 No.1

Perceptions of older adults and generativity among older citizens in Japan: a descriptive cross-sectional study

Yuho Shimizu,Tomoya Takahashi,Kenichiro Sato,Susumu Ogawa,Daisuke Cho,Yoshifumi Takahashi,Daichi Yamashiro,Yan Li,Keigo Hinakura,Ai Iizuka,Tomoki Furuya,Hiroyuki Suzuki 질병관리본부 2023 Osong Public Health and Research Persptectives Vol.14 No.5

Objectives: As the population ages worldwide, including in Japan, there is a growing expectation for older adults to remain active participants in society. The act of sharing one’s experiences and knowledge with younger generations through social engagement not only enriches the lives of older individuals, but also holds significant value for our society. In this study, we examined both positive and negative perceptions of older adults and investigated the correlation between these perceptions and generativity among older citizens. Additionally, we evaluated the impact of life satisfaction on these factors. Methods: We conducted a survey of 100 older adults in Japan (mean age, 71.68 years) and utilized multiple regression analyses, using positive and negative perceptions of older adults, life satisfaction, and demographic factors as independent variables. The sub-categories of generativity—namely, generative action, concern, and accomplishment—were used as dependent variables. Results: Participants who held a more positive perception of older adults demonstrated a higher level of generative actions and concerns. Additionally, participants who reported higher levels of life satisfaction also exhibited more generative actions, concerns, and accomplishments. Conversely, those who held a more negative perception of older adults were found to have higher levels of generative actions. Conclusion: Enhancing positive perceptions of older adults among them can boost the sub-categories of generativity. This study, which was conducted from an exploratory perspective, has several limitations, including a potential sampling bias. A more comprehensive examination of the relationship between perceptions of older adults and generativity is anticipated in future research.

Transformer Equivalent Model for Switching Transients Computation

Maekawa, Toshihiro,Nishiwaki, Susumu,Takahashi, Hideaki,Chigiri, Takeshi,Hosokawa, Osamu,Saida, Toshiyuki The Korean Institute of Electrical Engineers 2011 The Journal of International Council on Electrical Vol.1 No.4

We measured transient recovery voltage (TRV) in a 1500 MVA-525 kV/276 kV/63 kV transformer of the three-phase-in-one-tank type. We proved that TRV can be measured by interrupting the current generated by discharging a capacitor of low voltage through the transformer. The current was interrupted at its zero point by a diode at a low voltage. To calculate TRV via a computation, we developed a transformer equivalent model composed of a L-C multi-mesh circuit. The TRV waveform computed using the transformer equivalent model we developed agreed well with the measured TRV waveform.