共 47 条
Hypothalamic Leptin Signaling Regulates Hepatic Insulin Sensitivity via a Neurocircuit Involving the Vagus Nerve
被引:124
作者:

German, Jonathan
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机构:
Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA

Kim, Francis
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h-index: 0
机构:
Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA

Schwartz, Gary J.
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h-index: 0
机构:
Yeshiva Univ Albert Einstein Coll Med, Ctr Diabet Res & Training, Dept Med, Bronx, NY 10461 USA
Yeshiva Univ Albert Einstein Coll Med, Ctr Diabet Res & Training, Dept Neurosci, Bronx, NY 10461 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA

Havel, Peter J.
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h-index: 0
机构:
Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA

Rhodes, Christopher J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Chicago, Dept Med, Kovler Diabet Ctr, Chicago, IL 60637 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA

Schwartz, Michael W.
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h-index: 0
机构:
Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA

Morton, Gregory J.
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h-index: 0
机构:
Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA
机构:
[1] Univ Washington, Dept Med, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA
[2] Yeshiva Univ Albert Einstein Coll Med, Ctr Diabet Res & Training, Dept Med, Bronx, NY 10461 USA
[3] Yeshiva Univ Albert Einstein Coll Med, Ctr Diabet Res & Training, Dept Neurosci, Bronx, NY 10461 USA
[4] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA
[5] Univ Chicago, Dept Med, Kovler Diabet Ctr, Chicago, IL 60637 USA
基金:
美国国家卫生研究院;
关键词:
CAUDAL BRAIN-STEM;
FOOD-INTAKE;
GLUCOSE-PRODUCTION;
ARCUATE NUCLEUS;
BODY-WEIGHT;
CONGENITAL LIPODYSTROPHY;
RECEPTOR SUBSTRATE-2;
PERIPHERAL GLUCOSE;
BETA-CELLS;
RAT-BRAIN;
D O I:
10.1210/en.2009-0445
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Recent evidence suggests that hormones such as insulin and leptin act in the hypothalamus to regulate energy balance and glucose metabolism. Here we show that in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats, adenovirally induced expression of leptin receptors in the area of the hypothalamic arcuate nucleus improved peripheral insulin sensitivity via enhanced suppression of hepatic glucose production, with no change of insulin-stimulated glucose uptake or disposal. This effect was associated with increased insulin signal transduction via phosphatidylinositol-3-OH kinase (as measured by pY-insulin receptor substrate-1 and pS-PKB/Akt) in liver, but not skeletal muscle, and with reduced hepatic expression of the gluconeogenic genes, glucose-6-phosphatase and phosphoenolpyruvate kinase. Moreover, the beneficial effects of hypothalamic leptin signaling on hepatic insulin sensitivity were blocked by selective hepatic vagotomy. We conclude that hypothalamic leptin action increases peripheral insulin sensitivity primarily via effects on the liver and that the mechanism underlying this effect is dependent on the hepatic branch of the vagus nerve. (Endocrinology 150: 4502-4511, 2009)
引用
收藏
页码:4502 / 4511
页数:10
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Edelstein, EA
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA

Coppari, R
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA

Balthasar, N
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA

Cowley, MA
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA

Chua, S
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA

Elmquist, JK
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA

Lowelll, BB
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机构: Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA