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9. Intracellular calcium release channels: an update

Author

Santulli, Gaetano, Nakashima, Ryutaro, Yuan, Qi, Marks, Andrew R., Santulli, Gaetano, Nakashima, Ryutaro, Yuan, Qi, and Marks, Andrew R.

Subjects
Myocardium, Heart failure, Blood Pressure, Heart, Ryanodine Receptor Calcium Release Channel, Biochemistry, Special section reviews: Advances in calcium signalling, Hypertension, Diabetes Mellitus, Animals, Humans, Inositol 1,4,5-Trisphosphate Receptors, Calcium, Muscle, Skeletal, Intracellular calcium
Abstract

Ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP3Rs) are calcium (Ca(2+) ) release channels on the endo/sarcoplasmic reticulum (ER/SR). Here we summarize the latest advances in the field, describing the recently discovered mechanistic roles of intracellular Ca(2+) release channels in the regulation of mitochondrial fitness and endothelial function, providing novel therapeutic options for the treatment of heart failure, hypertension, and diabetes mellitus. This article is protected by copyright. All rights reserved.

Published
2017

14. Discovery of DS-1558: A Potent and Orally Bioavailable GPR40 Agonist

Author

Takano, Rieko, primary, Yoshida, Masao, additional, Inoue, Masahiro, additional, Honda, Takeshi, additional, Nakashima, Ryutaro, additional, Matsumoto, Koji, additional, Yano, Tatsuya, additional, Ogata, Tsuneaki, additional, Watanabe, Nobuaki, additional, Hirouchi, Masakazu, additional, Yoneyama, Tomoko, additional, Ito, Shuichiro, additional, and Toda, Narihiro, additional

Published
2015
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16. Report of a Joint Committee of the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: Inter-rater Agreement of Sputum Cytology for Lung Cancer Screening in Japan

Author

Sato, Masami, primary, Shiba, Mitsutoshi, additional, Saito, Yasuki, additional, Satoh, Yukitoshi, additional, Shibuya, Kiyoshi, additional, Tsuchida, Takaaki, additional, Nakayama, Tomio, additional, Horai, Takeshi, additional, Ikeda, Norihiko, additional, Kawahara, Ei, additional, Miura, Hiroyuki, additional, Nakashima, Ryutaro, additional, Taguchi, Akemi, additional, Yahata, Kazunobu, additional, Shimagaki, Nikako, additional, Kamio, Junko, additional, Nagao, Midori, additional, Miyake, Shinji, additional, Shimokawa, Yukihiro, additional, Tanaka, Ryota, additional, and Endo, Chiaki, additional

Published
2015
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17. Early hilar type lung cancer in Japan-A survey from January 2006 to December 2007-

Author

BABA, Masayuki, primary, IKEDA, Norihiko, additional, SAGAWA, Motoyasu, additional, IYODA, Akira, additional, HORAI, Takeshi, additional, NAKASHIMA, Ryutaro, additional, HIRATA, Tetsushi, additional, MIYAKE, Shinji, additional, SATO, Masami, additional, SAITO, Yasuki, additional, SHIBUYA, Kiyoshi, additional, NAKAYAMA, Tomio, additional, HIRANO, Takashi, additional, KONDO, Takashi, additional, KUSUNOKI, Yoko, additional, TADA, Hiroto, additional, FURUKAWA, Kinya, additional, and WATANABE, Yoichi, additional

Published
2012
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18. Early Hilar Type Lung Cancer in Japan: A Survey from January 2006 to December 2007

Author

Sato, Masami, primary, Saito, Yasuki, additional, Shibuya, Kiyoshi, additional, Nakayama, Tomio, additional, Hirano, Takashi, additional, Kondo, Takashi, additional, Baba, Masayuki, additional, Ikeda, Norihiko, additional, Sagawa, Motoyasu, additional, Iyoda, Akira, additional, Horai, Takeshi, additional, Nakashima, Ryutaro, additional, Hirata, Tetsushi, additional, Miyake, Shinji, additional, Kusunoki, Yoko, additional, Tada, Hiroto, additional, Furukawa, Kinya, additional, and Watanabe, Yoichi, additional

Published
2011
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23. Potent Antidiabetic Effects of Rivoglitazone, a Novel Peroxisome Proliferator–Activated Receptor-γAgonist, in Obese Diabetic Rodent Models

Author

Kanda, Shoichi, Nakashima, Ryutaro, Takahashi, Kanako, Tanaka, Jun, Ogawa, Junko, Ogata, Tsuneaki, Yachi, Makoto, Araki, Kazushi, and Ohsumi, Jun

Abstract

The pharmacological effects of rivoglitazone, a novel thiazolidinedione-derivative peroxisome proliferator–activated receptor (PPAR)-γagonist, were characterized in vitro and in vivo. Rivoglitazone activated human PPARγmore potently compared with rosiglitazone and pioglitazone and had little effect on PPARαand PPARδactivity in luciferase reporter assays. In Zucker diabetic fatty (ZDF) rats, 14-day administration of rivoglitazone decreased the plasma glucose and triglyceride (TG) levels in a dose-dependent manner. The glucose-lowering effect of rivoglitazone was much more potent than those of pioglitazone (ED50: 0.19 vs. 34 mg/kg) and rosiglitazone (ED50: 0.20 vs. 28 mg/kg). In addition, rivoglitazone showed potent antidiabetic effects in diabetic db/dbmice. In Zucker fatty rats, rivoglitazone at a dose of 0.1 mg/kg clearly ameliorated insulin resistance and lowered plasma TG levels by accelerating the clearance of plasma TG. Gene expression analysis in the liver and heart of ZDF rats treated with rivoglitazone for 14 days suggested that rivoglitazone may reduce hepatic glucose production and modulate the balance of the cardiac glucose/fatty acid metabolism in diabetic animals. In summary, we showed that rivoglitazone is a potent and selective PPARγagonist and has a potent glucose-lowering effect via improvement of the insulin resistance in diabetic animal models.

Published
2009
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25. The Effect of Rivoglitazone (Rivo) on Expression of Genes Targeted by PPARα and Those Implicated in Cardiac Function.

Author

Kanda, Shoichi, Tanaka, Jun, Takahashi, Kanako, Nakashima, Ryutaro, and Ohsumi, Jun

Subjects
HYPOGLYCEMIC agents, GENE expression, DIABETES, FATTY acids, BLOOD sugar, HOMEOSTASIS, LABORATORY rats
Abstract

Rivo is a novel PPARgamma agonist and potent antidiabetic agent. Expression of PPARalpha target genes and genes implicated in cardiac function was studied in the liver and heart of Zucker diabetic fatty rats treated with Rivo (1mg/kg) for 2 weeks, using pioglitazone (Pio; 100mg/kg), a PPARgamma agonist, and Wy-14,643 (Wy; 100mg/kg), a PPARalpha agonist, as comparators. Rivo and Pin normalized plasma concentrations of glucose, triglycerides (TG) and free fatty acids (FFA), while Wy decreased only plasma TG and FFA. In the heart and liver, Wy strongly increased expression of typical PPARalpha target genes such as acyl-coenzyme A oxidase 1 (ACO) and pyruvate dehydrogenase kinase 4 (PDK4), which may promote beta-oxidation of FFA as an energy source (Table). Rivo and Pio did not increase expression of these genes in the liver and Rivo decreased expression of ACO. In the heart, Rivo and Pin decreased the expression of ACO and medium chain acyl-CoA dehydrogenase (MCAD), suggesting reduced beta-oxidation of FFA and oxidative stress. They reduced expression of PDK4 and upregulated that of glucose transporter 4 (GLUT4) suggesting increased utilization of glucose. In addition, Rivo and Pin did not alter the expression of myosin heavy chain alpha and beta (MHCalpha and beta) or sarco/endoplasmic reticulum Ca[sup 2+] ATPase 2 (SERCA2), implicated in cardiac function. One week of treatment with Rivo (0.1 and 1mg/kg) or Wy (100mg/kg) reduced plasma TG primarily by accelerating TG clearance and reducing hepatic TG production, respectively. These results suggest that Rivo produces antidiabetic effects without augmenting the activity of PPARalpha and may have a desirable effect on cardiac function by improving cardiac energy homeostasis. Gene expression (% of control, meanSE; n=5, (*) p<0.05 vs control, ND=determined) [ABSTRACT FROM AUTHOR]

Published
2007

26. A small molecule K-3 promotes PDX1 expression and potentiates the differentiation of pluripotent stem cells into insulin-producing pancreatic β cells.

Author

Yano T, Shimaya Y, Enomoto T, Kiho T, Komoriya S, Nakashima R, Shiraki N, and Kume S

Abstract

Insulin-producing pancreatic β-like cells derived from human pluripotent stem cells (PSCs) are anticipated as a novel cell source for cell replacement therapy for diabetes patients. Here, we describe the identification of small molecule compounds that promote the differentiation of the PSCs into insulin-producing cells by high throughput screening with a chemical library composed of 55,000 compounds. The initial hit compound K-1 and one derivative K-3 increased the proportion of PSC-derived insulin-positive endocrine cells and their glucose-stimulated insulin secretory (GSIS) functions. K-3 preferentially acts on stage 3 pancreatic progenitor cells and increases the population expressing high levels of PDX1. As a result, the ratios of the PSC-derived PDX1 / NKX6.1 double-positive endocrine progenitor and INS / NKX6.1 double-positive mono-hormonal endocrine cells were increased. K-3 enhances the expression of functional pancreatic β cell markers and affects biological processes concerning organ development. K-3 also increased the yield of endocrine cells at the end of stage 5. The novel compound is a beneficial new tool for efficiently generating PSC-derived insulin-producing cells with high functionality and differentiation efficiency., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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