共查询到20条相似文献,搜索用时 46 毫秒
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Yusuke Nakatsu Hideyuki Sakoda Akifumi Kushiyama Hiraku Ono Midori Fujishiro Nanao Horike Masayasu Yoneda Haruya Ohno Yoshihiro Tsuchiya Hideaki Kamata Hidetoshi Tahara Toshiaki Isobe Fusanori Nishimura Hideki Katagiri Yoshitomo Oka Toshiaki Fukushima Shin-Ichiro Takahashi Hiroki Kurihara Takafumi Uchida Tomoichiro Asano 《The Journal of biological chemistry》2010,285(43):33018-33027
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Coordination of skeletal muscle growth and metabolism with nutrient availability is critical for metabolic homeostasis. To establish the role of insulin-like signaling in this process, we used muscle creatine kinase (MCK)-Cre to disrupt expression of insulin receptor substrates Irs1 and Irs2 in mouse skeletal/cardiac muscle. In 2-week-old mice, skeletal muscle masses and insulin responses were slightly affected by Irs1, but not Irs2, deficiency. In contrast, the combined deficiency of Irs1 and Irs2 (MDKO mice) severely reduced skeletal muscle growth and Akt→mTOR signaling and caused death by 3 weeks of age. Autopsy of MDKO mice revealed dilated cardiomyopathy, reflecting the known requirement of insulin-like signaling for cardiac function (P. G. Laustsen et al., Mol. Cell. Biol. 27:1649-1664, 2007). Impaired growth and function of MDKO skeletal muscle were accompanied by increased Foxo-dependent atrogene expression and amino acid release. MDKO mice were resistant to injected insulin, and their isolated skeletal muscles showed decreased insulin-stimulated glucose uptake. Glucose utilization in MDKO mice and isolated skeletal muscles was shifted from oxidation to lactate production, accompanied by an elevated AMP/ATP ratio that increased AMP-activated protein kinase (AMPK)→acetyl coenzyme A carboxylase (ACC) phosphorylation and fatty acid oxidation. Thus, insulin-like signaling via Irs1/2 is essential to terminate skeletal muscle catabolic/fasting pathways in the presence of adequate nutrition. 相似文献
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Horike N Sakoda H Kushiyama A Ono H Fujishiro M Kamata H Nishiyama K Uchijima Y Kurihara Y Kurihara H Asano T 《The Journal of biological chemistry》2008,283(49):33902-33910
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TORC1 and TORC2 converge to regulate the SAGA co‐activator in response to nutrient availability 下载免费PDF全文
Thomas Laboucarié Dylane Detilleux Ricard A Rodriguez‐Mias Céline Faux Yves Romeo Mirita Franz‐Wachtel Karsten Krug Boris Maček Judit Villén Janni Petersen Dominique Helmlinger 《EMBO reports》2017,18(12):2197-2218
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Sadagurski M Leshan RL Patterson C Rozzo A Kuznetsova A Skorupski J Jones JC Depinho RA Myers MG White MF 《Cell metabolism》2012,15(5):703-712
Irs2-mediated insulin/IGF1 signaling in the CNS modulates energy balance and glucose homeostasis; however, the site for Irs2 function is unknown. The hormone leptin mediates energy balance by acting on leptin receptor (LepR-b)-expressing neurons. To determine whether LepR-b neurons mediate the metabolic actions of Irs2 in the brain, we utilized Lepr(cre) together with Irs2(L/L) to ablate Irs2 expression in LepR-b neurons (Lepr(ΔIrs2)). Lepr(ΔIrs2) mice developed obesity, glucose intolerance, and insulin resistance. Leptin action was not altered in young Lepr(ΔIrs2) mice, although insulin-stimulated FoxO1 nuclear exclusion was reduced in Lepr(ΔIrs2) mice. Indeed, deletion of Foxo1 from LepR-b neurons in Lepr(ΔIrs2) mice normalized energy balance, glucose homeostasis, and arcuate nucleus gene expression. Thus, Irs2 signaling in LepR-b neurons plays a crucial role in metabolic sensing and regulation. While not required for leptin action, Irs2 suppresses FoxO1 signaling in LepR-b neurons to promote energy balance and metabolism. 相似文献
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Dehydrozingerone exerts beneficial metabolic effects in high‐fat diet‐induced obese mice via AMPK activation in skeletal muscle 下载免费PDF全文
Su Jin Kim Hong Min Kim Eun Soo Lee Nami Kim Jung Ok Lee Hye Jeong Lee Na Yeon Park Joo Yeon Jo Bo Young Ham Si Hyun Han Sun Hwa Park Choon Hee Chung Hyeon Soo Kim 《Journal of cellular and molecular medicine》2015,19(3):620-629
Dehydrozingerone (DHZ) exerts beneficial effects on human health; however, its mechanism of action remains unclear. Here, we found that DHZ suppressed high‐fat diet‐induced weight gain, lipid accumulation and hyperglycaemia in C57BL/6 mice and increased AMP‐activated protein kinase (AMPK) phosphorylation and stimulated glucose uptake in C2C12 skeletal muscle cells. DHZ activated p38 mitogen‐activated protein kinase (MAPK) signalling in an AMPK‐dependent manner. Inhibiting AMPK or p38 MAPK blocked DHZ‐induced glucose uptake. DHZ increased GLUT4 (major transporter for glucose uptake) expression in skeletal muscle. Glucose clearance and insulin‐induced glucose uptake increased in DHZ‐fed animals, suggesting that DHZ increases systemic insulin sensitivity in vivo. Thus, the beneficial health effects of DHZ could possibly be explained by its ability to activate the AMPK pathway in skeletal muscle. 相似文献
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Gustavo A. Santos Vinícius D. Pereira Erika A. F. R. Roman Leticia Ignacio-Souza Daniele C. Vitorino Rodrigo Ferreira de Moura Daniela S. Razolli Adriana S. Torsoni Licio A. Velloso Marcio A. Torsoni 《PloS one》2013,8(4)