Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.

Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Research Abstract Details 

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Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Abstract Text:

Decheng Ren,Yingjiang Zhou,David Morris,Minghua Li,Zhiqin Li,Liangyou Rui,

SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2 and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta) were expressed in numerous tissues, including the brain, hypothalamus, liver, muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice expressing SH2B1 only in neural tissue but not in other tissues. Systemic deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice, including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia, insulin resistance, and glucose intolerance. Neuron-specific restoration of SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic neuropeptide expression in the hypothalamus. Moreover, neuron-specific overexpression of SH2B1 dose-dependently protected against high-fat diet-induced leptin resistance and obesity. These observations suggest that neuronal SH2B1 regulates energy balance, body weight, peripheral insulin sensitivity, and glucose homeostasis at least in part by enhancing hypothalamic leptin sensitivity.

Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Publishing Authors By Initials

D Ren,Y Zhou,D Morris,M Li,Z Li,L Rui,

For similar nutritional and metabolic diseases: nutrition disorders: overnutrition: obesity research abstracts see: nutritional and metabolic diseases: nutrition disorders: overnutrition: obesity research

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MEDLINE DATE:

Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of clinical investigation

VOLUME: 117

Page Numbers: 397-406

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 18

MONTH: 01

YEAR: 2007

Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Keywords Mesh Terms:

KEYWORDS: Obesity

MESH TERMS: metabolism

Chemical & Substance for Abstract: Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Information

Substance Name: Glucose

Registry Number: 50-99-7

Grant and Affiliation Information for Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.

AFFILIATION: Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0622, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32 GM008322

ACRONYM: GM

MEDLINETA: J Clin Invest

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