@article{8a817df3f26f4a73883d23c0895d4492,
title = "Dynamic Functional Relay between Insulin Receptor Substrate 1 and 2 in Hepatic Insulin Signaling during Fasting and Feeding",
abstract = "Insulin receptor substrate (Irs) mediates metabolic actions of insulin. Here, we show that hepatic Irs1 and Irs2 function in a distinct manner in the regulation of glucose homeostasis. The PI3K activity associated with Irs2 began to increase during fasting, reached its peak immediately after refeeding, and decreased rapidly thereafter. By contrast, the PI3K activity associated with Irs1 began to increase a few hours after refeeding and reached its peak thereafter. The data indicate that Irs2 mainly functions during fasting and immediately after refeeding, and Irs1 functions primarily after refeeding. In fact, liver-specific Irs1-knockout mice failed to exhibit insulin resistance during fasting, but showed insulin resistance after refeeding; conversely, liver-specific Irs2-knockout mice displayed insulin resistance during fasting but not after refeeding. We propose the concept of the existence of a dynamic relay between Irs1 and Irs2 in hepatic insulin signaling during fasting and feeding.",
keywords = "HUMDISEASE",
author = "Naoto Kubota and Tetsuya Kubota and Shinsuke Itoh and Hiroki Kumagai and Hideki Kozono and Iseki Takamoto and Tomoka Mineyama and Hitomi Ogata and Kumpei Tokuyama and Mitsuru Ohsugi and Takayoshi Sasako and Masao Moroi and Kaoru Sugi and Shigeru Kakuta and Yoichiro Iwakura and Tetsuo Noda and Shin Ohnishi and Ryozo Nagai and Kazuyuki Tobe and Yasuo Terauchi and Kohjiro Ueki and Takashi Kadowaki",
note = "Funding Information: We thank Katsuyoshi Kumagai, Katsuko Takasawa, Eri Yoshida-Nagata, Namiko Kasuga, Miharu Nakashima, Ayumi Nagano, Sayaka Sasamoto, Yuko Miki, Ritsuko Fujita, Norie Ohtsuka-Kowatari, Eishin Hirata, and Hiroshi Chiyonobu for their excellent technical assistance and assistance with the animal care. This work was supported by a grant for CREST from Japan Science and Technology Corporation; a grant for Promotion of Fundamental Studies in Health Science of the Organization for Pharmaceutical Safety and Research; a grant for TSBMI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a Grant-in-aid for Scientific Research in Priority Areas (A) (16209030) and (A) (18209033) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to T. K.); and a Grant-in-aid for Scientific Research in Priority Areas (C) (19591037) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to N. K.). We certify that none of the authors of this manuscript have any financial interests to declare in relation to this work. ",
year = "2008",
month = jul,
day = "2",
doi = "10.1016/j.cmet.2008.05.007",
language = "英語",
volume = "8",
pages = "49--64",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}