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Protein tyrosine phosphatase 1B (PTP1B) and SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) have been shown in mice to regulate metabolism via the central nervous system, but the specific neurons mediating these effects are unknown. Here, we have shown that proopiomelanocortin (POMC) neuron-specific deficiency in PTP1B or SHP2 in mice results in(More)
The FDA-approved glucagon-like-peptide-1 receptor (GLP-1R) agonists exendin-4 and liraglutide reduce food intake and body weight. Nausea is the most common adverse side effect reported with these GLP-1R agonists. Whether food intake suppression by exendin-4 and liraglutide occurs independently of nausea is unknown. Further, the neurophysiological mechanisms(More)
Protein tyrosine phosphatase 1B (PTP1B) is a ubiquitously expressed tyrosine phosphatase implicated in the negative regulation of leptin and insulin receptor signaling. PTP1B(-/-) mice possess a lean metabolic phenotype attributed at least partially to improved hypothalamic leptin sensitivity. Interestingly, mice lacking both leptin and PTP1B(More)
Cancer chemotherapy drugs, such as cisplatin, potently produce nausea and vomiting. Acute effects of these treatments are partly controlled by antiemetic drugs, but the delayed effects (>24 h), especially nausea, are more difficult to treat. It is unknown what brain pathways produce this delayed sickness. Our prior data show that brain Fos expression is(More)
The incretin and food intake suppressive effects of intraperitoneally administered glucagon-like peptide-1 (GLP-1) involve activation of GLP-1 receptors (GLP-1R) expressed on vagal afferent fiber terminals. Central nervous system processing of GLP-1R-driven vagal afferents results in satiation signaling and enhanced insulin secretion from(More)
Leptin regulates energy balance through central circuits that control food intake and energy expenditure, including proopiomelanocortin (POMC) neurons. POMC neuron-specific deletion of protein tyrosine phosphatase 1B (PTP1B) (Ptpn1(loxP/loxP) POMC-Cre), a negative regulator of CNS leptin signaling, results in resistance to diet-induced obesity and improved(More)
CCK-A receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and develop obesity and Type 2 diabetes. In this strain, taste preference functions have not been investigated. Therefore, a series of short-access, two-bottle tests were performed in age-matched prediabetic OLETF and nonmutant Long-Evans Tokushima Otsuka (LETO) rats to(More)
Cocaine addiction continues to be a significant public health problem for which there are currently no effective FDA-approved treatments. Thus, there is a clear need to identify and develop novel pharmacotherapies for cocaine addiction. Recent evidence indicates that activation of glucagon-like peptide-1 (GLP-1) receptors in the ventral tegmental area (VTA)(More)
Glucagon-like peptide-1 receptor (GLP-1R) activation within the nucleus tractus solitarius (NTS) suppresses food intake and body weight (BW), but the intracellular signals mediating these effects are unknown. Here, hindbrain (fourth i.c.v.) GLP-1R activation by Exendin-4 (Ex-4) increased PKA and MAPK activity and decreased phosphorylation of AMPK in NTS.(More)
Accumulating evidence has indicated a link between dopamine signaling and obesity in both animals and humans. We have recently demonstrated heightened avidity to sapid sweet solutions in the obese cholecystokinin (CCK)-1 receptor deficient Otsuka Long Evans Tokushima fatty (OLETF) rat. To investigate the dopamine dependence and the respective contribution(More)