Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver

被引：181

作者：

Imai, Junta ^{[2
]}

Katagiri, Hideki ^{[1
]}

Yamada, Tetsuya ^{[2
]}

Ishigaki, Yasushi ^{[2
]}

Suzuki, Toshinobu ^{[1
,2
]}

Kudo, Hirohito ^{[1
,2
]}

Uno, Kenji ^{[1
]}

Hasegawa, Yutaka ^{[2
]}

Gao, Junhong ^{[1
]}

Kaneko, Keizo ^{[1
,2
]}

Ishihara, Hisamitsu ^{[2
]}

Niijima, Akira ^{[3
]}

Nakazato, Masamitsu ^{[4
]}

Asano, Tomoichiro ^{[5
]}

Minokoshi, Yasuhiko ^{[6
]}

Oka, Yoshitomo ^{[2
]}

机构：

[1] Tohoku Univ, Grad Sch Med, Div Adv Therapeut Metab Dis, Ctr Translat & Adv Anim Res, Sendai, Miyagi 9808575, Japan

[2] Tohoku Univ, Grad Sch Med, Div Mol Metab & Diabet, Sendai, Miyagi 9808575, Japan

[3] Niigata Univ, Sch Med, Niigata 9518150, Japan

[4] Miyazaki Univ, Miyazaki Med Coll, Dept Internal Med 3, Miyazaki 8891692, Japan

[5] Hiroshima Univ, Grad Sch Med, Dept Med Sci, Hiroshima, Japan

[6] Natl Inst Physiol Sci, Div Endocrinol & Metab, Dept Dev Physiol, Okazaki, Aichi 444, Japan

来源：

SCIENCE | 2008年 / 322卷 / 5905期

关键词：

D O I：

10.1126/science.1163971

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Metabolic regulation in mammals requires communication between multiple organs and tissues. The rise in the incidence of obesity and associated metabolic disorders, including type 2 diabetes, has renewed interest in interorgan communication. We used mouse models to explore the mechanism whereby obesity enhances pancreatic beta cell mass, pathophysiological compensation for insulin resistance. We found that hepatic activation of extracellular regulated kinase (ERK) signaling induced pancreatic b cell proliferation through a neuronal- mediated relay of metabolic signals. This metabolic relay from the liver to the pancreas is involved in obesity- induced islet expansion. In mouse models of insulin- deficient diabetes, liver- selective activation of ERK signaling increased b cell mass and normalized serum glucose levels. Thus, interorgan metabolic relay systems may serve as valuable targets in regenerative treatments for diabetes.

引用

页码：1250 / 1254

页数：5

共 24 条

[1] Anatomy and function of sensory hepatic nerves [J].