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ラット褐色脂肪組織におけるグルコース利用とグルコーストランスポーターのアドレナリン性調節
| Title: | ラット褐色脂肪組織におけるグルコース利用とグルコーストランスポーターのアドレナリン性調節 |
| Other Titles: | Adrenergic Regulation of Glucose Utilization and Glucose Transporter in Rat Brown Adipose Tissue |
| Authors: | 二上, 英樹1 Browse this author |
| Authors(alt): | Nikami, Hideki1 |
| Issue Date: | 25-Mar-1998 |
| Publisher: | Hokkaido University |
| Abstract: | Most mammals have two types of adipose tissues. White adipose tissue is the site for energy storage, whereas brown adipose tissue(BAT) for energy dissipation: that is, this is the major site of nonshivering heat production during cold acclimation, spontaneous overfeeding, and arousal from hibeination. The metabolic activation and subsequent heat production in BAT are primarily controlled by sympathetic nerves distributed abundantly to this tissue. Although the main substrate for BAT thermogenesis is fatty acids derived from intracellular triglyceride, glucose metabolism in BAT is also activated by the sympathetic nerves. In order to clarify the regulatory mechanism of BAT glucose metabolism, in this study, I examined the effcts of cold exposure and adrenergic sdmulation on tissue glucose utilization and glucose transporter both in vivo using the rat as an experimental animal and in vitro using a primary culture cell system. Exposure of rats to a cold environment at 4℃ for 10 days increased the uptake of 2-deoxy-D-glucose, an index of cellular glucose utilization, remarkably in BAT. In parallel with tissue glucose utilization, the protein and mRNA levels of an insulin-responsive glucose transporter GLUT4, which is the major glucose transporter in rat adipose tissues, were also increased after cold exposure. The stmulative effects of cold exposure on BAT glucose utilization and GLUT4 expression were completely abolished when sympathetic nerves into BAT had been surgically severed, but were mimicked when noradrenaline was admmistered continuously using an osmotic mini-pump for 10 days at 24℃. Continuous admmistration of a β-adrenergic agonist (isoproterenol) was as effective as noradrenaline, whereas an α-adrenergic agonist (phenylephrine) showed no effect. In contrast to BAT, in other insulin-sensitive tissues such as white adipose tissue, skeletal muscle and heart, neither cold exposure nor adrenergic agonist-treatment showed noticeable effects on tissue glucose utilization and GLUT4. From these results, it was concluded that the stimulative effect of cold exposure on glucpse utilization in BAT is based on the increased synthesis of GLUT4 protein evoked by the β-adrenergic action of noradrenaline released from sympathetic nerve entering to this tissue. To confirm the above results obtained from the in vivo experiments and to investigate the molecular mechanism of the β-adrenergic action on BAT glucose utilization, next, some in vitro experiments were perfomled using a primary culture system of brown adipocytes, with special reference to adrenoceptors. Precursor cells of brown adipocytes were isolated from the interscapular BAT of newborn rats and cultured on collagen-coated dishes. When confluent cells were treated with dexamethasone, mRNAs for GLUT4, hormone-sensitive lipase, and CCAAT/enhancer binding protein α were increased remarkably, indicating a predominant effect of dexamethasone on the terminal differentiation of the cultured cell. BAT has an adipocyte-specific β-adrenoceptor(β3) in addition to β1- and β2-adrenoceptors. Effects of dexamethasone on the expression of three subtypes of β-adrenoceptor were also examined. β1-and β2-adrenoceptor mRNA remained constant regardless of dexamethasone-treatment, while β3-adrenoceptor mRNA was present only in dexamethasone-treated differentiated cells. To assess the metabolic response mediated by β3-adrenoceptor, glucose transport into the cells was estimated. Noradrenaline enhanced glucose transport in dexamethasone-treated differentiated cells, but not in undifferentiated cells. β3-adrenergic agonists mimicked completely the stmulatory effect of noradrenaline at concentrations lower by two orders of magnitude. These results suggest that the β3-adrenoceptor plays a significant role in the response of glucose transport to adrenergic stimulation. |
| Conffering University: | 北海道大学 |
| Degree Report Number: | 乙第5325号 |
| Degree Level: | 博士 |
| Degree Discipline: | 獣医学 |
| Type: | theses (doctoral) |
| URI: | http://hdl.handle.net/2115/51518 |
| Appears in Collections: | 学位論文 (Theses) > 博士 （獣医学）
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Submitter: 二上 英樹
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