Current Research:
The Rui laboratory investigates the physiological and molecular mechanisms of obesity and type 2 diabetes. Normal body weight is maintained by a balance between energy intake (food intake) and energy expenditure. Chronic energy imbalance results in obesity due to the accumulation of excess energy as triglycerides in adipose tissue. The brain, particularly the hypothalamus, controls energy balance and body weight by sensing and integrating various metabolic signals, including hormones (e.g. leptin and insulin) and nutrients (e.g. glucose and lipids). The ability of the hypothalamus to sense and integrate these signals is regulated by both genetic and environmental factors; impairment in this sensitivity is a key determinant for energy imbalance and obesity. We study signal transduction pathways in hypothalamic neurons that regulate energy homeostasis and body weight, and investigate molecular defects in the hypothalamic neural circuits that impair the ability of the hypothalamus to sense and integrate metabolic signals and to control energy balance and body weight (e.g. leptin resistance).
Obesity is the primary risk factor for type 2 diabetes. Type 2 diabetes is caused by defects in both insulin production and insulin action (e.g. insulin resistance in the liver, muscle, fat and brain). Insulin is secreted by pancreatic b cells in response to glucose, and reduces blood glucose both by stimulating glucose uptake into skeletal muscle and adipocytes and by suppressing glucose production in the liver. Importantly, adipose tissue produces and secretes a variety of bioactive substrates (e.g. adipokines) that regulate insulin sensitivity and glucose/lipid metabolism in other tissues. Obesity is associated with both insulin resistance and b cell dysfunction. We study b cell regeneration, insulin secretion, adipose endocrine function, the hepatic gluconeogenic and lipogenic programs, and the molecular mechanism of insulin resistance.
We have identified SH2B1, NIK and SLUG as key regulators of body weight and glucose/lipid metabolism. We found that the genetic deletion of SH2B1 impairs leptin and insulin signal transduction, thereby resulting in energy imbalance, obesity, and type 2 diabetes in mice. We have developed multiple genetic (e.g. tissue-specific knockout), physiological (e.g. metabolic phenotyping), immunohistochemical, and molecular/biochemical (e.g. gene silencing and molecular imaging) methods. Our goal is to elucidate the mechanisms of energy homeostasis and glucose homeostasis, and to identify potential drug targets for the treatment of obesity and type 2 diabetes.
Recent Publications:
Zhiqin Li, Yingjiang Zhou, Christin Carter-Su, Martin G. Myers Jr. and Liangyou Rui. SH2B1 enhances leptin signaling by both Janus Kinase 2 Tyr813-dependent and -independent mechanisms. Molecular Endocrinology. 21(9): 2270-2281; 2007
Liangyou Rui. A link between protein translation and body weight. Journal of Clinical Investigation. 117: 310-313; 2007
Decheng Ren, Yingjiang Zhou, David Morris, Minghau Li, Zhiqin Li, and Liangyou Rui. Neuronal SH2B1 is essential for controlling energy and glucose homeostasis. Journal of Clinical Investigation. 117: 397-406; 2007
Minghua Li, Zhiqin Li, David Morris and Liangyou Rui. Identification of SH2B2b as an inhibitor for SH2B1- and SH2B2a-promoted Janus Kinase-2 activation and insulin signaling. Endocrinology.148(4): 1615-1621; 2007
Minghua Li, Decheng Ren, Masanori Iseki, Satoshi Takaki, and Liangyou Rui. Differential Role of SH2-B and APS in Regulating Energy and Glucose Homeostasis. Endocrinology. 147(5):2163-2170; 2006
Decheng Ren, Minghua Li, Chaojun Duan, and Liangyou Rui. Identification of SH2-B as a key regulator of leptin sensitivity, energy balance, and body weight in mice. Cell Metabolism. 2:95-104; 2005
Chaojun Duan, Minghua Li, Liangyou Rui. SH2-B promotes insulin receptor 1 (IRS1)- and IRS2-mediated activation of the PI 3-kinase pathway in response to leptin. Journal of Biological Chemistry. 279(42):43684-91; 2004
Chaojun Duan, Hongyan Yang, Morris F. White, Liangyou Rui. Disruption of the SH2-B gene causes age-dependent insulin resistance and glucose intolerance. Molecular and Cellular Biology. 24(17): 7435-7443; 2004
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