期刊
MOLECULAR METABOLISM
卷 3, 期 1, 页码 55-63出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molmet.2013.10.004
关键词
insulin receptor substrate 2; Insulin receptor substrate 4; Leptin; Obesity; Nutrient homeostasis; Energy balance
资金
- NIDDK NIH HHS [R01 DK038712, P30 DK020572, R01 DK055326, R01 DK098655, R37 DK056731, R01 DK056731, R01 DK057768] Funding Source: Medline
- NIGMS NIH HHS [P50 GM021700] Funding Source: Medline
Insulin receptor substrates (Irs1, 2, 3 and Irs4) mediate the actions of insulin/IGF1 signaling. They have similar structure, but distinctly regulate development, growth, and metabolic homeostasis. Irs2 contributes to central metabolic sensing, partially by acting in leptin receptor (LepRb)-expressing neurons. Although Irs4 is largely restricted to the hypothalamus, its contribution to metabolic regulation is unclear because Irs4-null mice barely distinguishable from controls. We postulated that Irs2 and Irs4 synergize and complement each other in the brain. To examine this possibility, we investigated the metabolism of whole body Irs4(-/y) mice that lacked Irs2 in the CNS (bIrs2(-/-) . Irs4(-/y)) or only in LepRb-neurons (Lepr(Delta Irs2) . Irs4(-/y)) . bIrs2(-/-) . Irs4(-/y) mice developed severe obesity and decreased energy expenditure, along with hyperglycemia and insulin resistance. Unexpectedly, the body weight and fed blood glucose levels of Lepr(Delta Irs2) . Irs4(-/y) mice were not different from Lepr(Delta Irs2) mice, suggesting that the functions of Irs2 and Irs4 converge upon neurons that are distinct from those expressing LepRb. (C) 2013 The Authors. Published by Elsevier GmbH. (C) 2013 The Authors. Published by Elsevier GmbH. Open access under CC BY-NC-ND license.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据