| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
RecentIy, it was reported that centraI abministrati of GLP-l decreased food intake in rats. The amino acid sequences of GLP-1 are identical in all mammals, and chicken GLP-1 exhibits a high homology with mammalian GLP-1. The aim of first experiment was to elucidate whether central injection of mammalian or chicken GLP-l inhibits food intake in the chick, and to compare their effects. IntracerebroventricuIar administration of mammalian and chicken GLP-1 strongly inhibited food intake of chicks. However, the suppressive effect of both GLP-1 on food intake was similar. These results show that GLP-1 with a variety of amino acid sequences may be the most potent inhibitor of food intake in the chicken. The aim of second experiment was to elucidate whether suppressed food intake by central injection of GLP-1 would be modified by an appetite stimulant such as fasting and neuropeptide Y (MN). Birds starved for 6 h ate significantly more food than those starved for 3 h, while irrespective of the
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time for fasting GLP-1 strongly inhibited food intake as rapidly as 10 min after i.c.v injection., Central administration of NPY greatly enhanced food intake, but co-injection of GIP-1 (0.1,02 or 0.3 IOTAg/1O IOTA1) decreased food Intake in a dose-dependent fashion. The aim of third experiment was to elucidate whether the suppression of food intake induced by central injection of GLP-1 is mediated by activation of the hypothalamic-pituitary-adrenal axis. Fist, the effects of central administration of corticotropin-reIeasing factor (CRF) were investigated CRF strongly inhibited food intake. Thereafter, effects of central CRF or GLP-1 on plasma corticosterone concentration were examined CRF significantly stimulated corticosterone release, but GLP- I did not alter plasma corticosterone concentration These results suggest that CRF is a potent inhibitor of food intake in the chick, but the suppression of food intake induced by central GLP-1 may not involve the activation of hypothaIamic -pituitary-adrenal axis. Furthermore, it was dear that C-terminal amino acids of GLP-1(7-36) have an important role for the bioactivity in the central nervous system with special reference to feeding behavior in the fourth experiment and that modification of a part of ammo acid sequence of exendin (9-39) may be required to antagonize chicken GLP-1 receptor in fifth experiment Less
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