Possible Involvement of Hypothalamic Nucleobindin-2 in Hyperphagic Feeding in Tsumura Suzuki Obese Diabetes Mice
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概要
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The aim of this study was to clarify the hypothalamic neuropeptides that are associated with hyperphagic feeding in Tsumura Suzuki Obese Diabetes (TSOD) mice, a model of type 2 diabetes with polygenic abnormalities. TSOD mice showed an increase in body weight and hyperleptinemia from 1 month of age and hyperphagic feeding, hyperglycemia, hyperlipidemia and hyperinsulinemia from 3 to 12 months of age compared with age-matched non-diabetic control Tsumura Suzuki Non Obesity (TSNO) mice. The mRNA level of nucleobindin-2 (NUCB2), the precursor of the anorexigenic neuropeptide nesfatin-1, was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice from 3 to 12 months of age. The protein level of NUCB2 was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice at 3 months of age. The mRNA levels of galanin, melanin-concentrating hormone, neuropeptide Y, and pro-opiomelanocortin were significantly changed in the hypothalamus in TSOD mice at several time points. Another model of type 2 diabetes, db/db mice, which is a mutant mouse that lacks a functional leptin receptor, showed hyperphagic feeding but no change in hypothalamic NUCB2 mRNA compared with non-diabetic control db/+ mice. The results suggest that the disrupted control of hypothalamic NUCB2-mediated signaling may contribute to hyperphagic feeding in TSOD mice. In addition, the mechanism for the development of hyperphagic feeding in TSOD mice is different than that in db/db mice.
- 公益社団法人 日本薬学会の論文
著者
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Kawada Tomie
Department of Clinical Pharmacy, Faculty of Pharmacy, Musashino University
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Miyata Shigeo
Research Institute of Pharmaceutical Sciences, Musashino University
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Yamada Nao
Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University
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KAWADA Tomie
Department of Clinical Pharmacology, Faculty of Pharmacy, Musashino University
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Miyata Shigeo
Research Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Musashino University
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Kawada Tomie
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences
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