| Project/Area Number |
01570161
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Ehime University |
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Principal Investigator |
SHIMAZU Takashi (1990) Ehime School of University Medicine, Professor, 医学部, 教授 (30090400)
高橋 章 (1989) 愛媛大学, 医学部, 助手 (40171467)
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| Co-Investigator(Kenkyū-buntansha) |
IWAI Masaru Ehime School of University Medicine, Assistant Professor, 医学部, 助手 (00184854)
OKUMURA Nobuaki Ehime School of University Medicine, Assistant Professor, 医学部, 助手 (20224173)
嶋津 孝 愛媛大学, 医学部, 教授 (30090400)
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| Project Period (FY) |
1989 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Glucose transporter / Tissue glucose uptake / Cytochalasin B binding / Ventromedial hypothalamus / Sympathetic nerve / Brown adipose tissue / Heart muscle / Sarcolemmal membrane / 糖輸送活性 / 骨格筋 / 視床下部腹内側核(VMH) / 2-デオキシグルコ-ス / 糖の取り込み / 糖輸送体動態 / 心筋,骨格筋 / 褐色脂肪組織(BAT) |
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| Research Abstract |
To clarify the role of the ventromedial hypothalamus (VMH) -sympathetic nervous system in insulin-independent glucose transport in peripheral tissues, tissue glucose uptake was assessed in vivo by the 2-[^3H]deoxyglucose method during electrical and chemical stimulation of the VMH in anesthetized rats. VMH stimulation increased the rate constant of glucose uptake in brown adipose tissue (BAT) (about 10-fold), heart (3-fold) and skeletal muscles (1.5-fold), but not in white adipose tissue, diaphragm and brain. The effect of VMH stimulation on glucose uptake in BAT was abolished by local sympathetic denervation, indicating that the increase in glucose uptake is mediated by the sympathetic nerves. Electrical stimulation of the lateral hypothalamus, on the other hand, had no appreciable effects on 2-[^3H] deoxyglucose uptake in any tissues.
The mechanism of hypothalamic effect on glucose uptake was analyzed by measuring D-glucose transport in vitro, using sarcolemmal membrane vesicles isolated from heart muscle. Non-specific L-glucose transport was subtracted from D-glucose value to obtain specific D-glucose transport. It was found that VMH stimulation caused significant increase in D-glucose transport in heart plasma membrane, as observed after insulin treatment.
Changes in glucose transporters after VMH stimulation were also examined by the [^3H] cytochalasin B binding method using heart sarcolemmal membrane. Scatchard analysis of cytochalasin B binding indicated that VMH stimulation did not alter both the number and affinity (dissociation constant) of glucose transporters in the heart sarcolemmal membrane, whereas insulin administration increased the number of transporters in the membrane. These results suggest that the mechanism by which VMH-sympathetic nervous system enhances glucose uptake in certain tissues is different from that of insulin, probably deriving from an activation of glucose transporter molecule in the plasma membrane.
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