著者

TOSHIAKI TANAKA YOSHIKI SEINO KENJI FUJIEDA YUTAKA IGARASHI SUSUMU YOKOYA KATSUHIKO TACHIBANA YUNOSUKE OGAWA

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.46, no.4, pp.605-612, 1999 (Released:2006-11-25)

参考文献数

20

被引用文献数

4 5

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To evaluate pharmacokinetics of growth hormone (GH) and its effects on IGF-I, glucose, insulin, nonesterified fatty acid (NEFA) and riglyceride (TG), fifteen Japanese healthy adult male volunteers (20-27 years old) were studied. The subjects were divided into three groups, and received with a single s.c. injection of 0.075, 0.15 and 0.30IU/kg of GH, respectively. The subjects assigned to receive 0.30IU/kg were administered for additional 6 days. After a single administration of GH, Cmax and AUC of GH were increased in a dose-dependent manner. There was a significant positive correlation between the AUC and the T1/2 (r=0.516, P<0.05). Total body clearance was significantly greater in 0.075IU/kg group than the other groups and showed a significant negative correlation with Cmax (r=-0.694, P<0.005) and AUC (r=-0.723, P<0.005). After a single administration of each dose, serum IGF-I concentrations were increased gradually. In the repeated administered group (0.30IU/kg), IGF-I concentrations almost reached a plateau at a significantly high level four days after the start of administration and remained at a high level (786-405.4ng/ml) until day 8. There was no significant difference in diurnal change of blood glucose and serum insulin after a single administration of GH among three groups. In the 0.3U/kg group, there was no significant difference in diurnal change of blood glucose between day 1 and day 7, but serum insulin level was significantly higher in day 7 than in day 1 (P<0.01). Serum concentrations of NEFA were increased over time after administration in all subjects administered once or repeatedly. TG concentrations showed no changes after single administration of each dose level, but were significantly increased on day 7 in the subjects repeatedly treated with 0.30 IU/kg/day. This effect is speculated to be caused by high dose GH treatment. The above findings demonstrated that higher GH dose significantly influences on carbohydrate and lipid metablism. It remains necessary to elucidate what kinds of effects of the long-lasting increased levels of insulin and triglyceride, even if reversible, would have on glucose and lipid metabolism.