5 糖の膜透過に対するホルモン性調節

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The theory that insulin acts to facilitate the transmembrane transport of sugars possessing the same configuration as d-glucose about carbons 1, 2 and 3 has received substantial support from subsequent confirmatory observations, which have added another important point that insulin-sensitive sugar transfer occurs only in the membranes which restrict the entry of glucose into cells in the absence of insulin. This fact has led us to assume that the facilitation of stereospecific sugar transfer should be caused by other peptide hormones than insulin in their target organs so long as the membranes of the organs confine sugars to a small fraction of intracellular water in the absence of the hormones concerned. In this respect, characteristics of sugar transport were investigated in the bisected rabbit adrenal preparations, showing that the difference between water-H3 space and 1-arabinose-1-C14 space remains constant and 1-arabinose space is always in close proximity to sucrose space, i.e. the extracellular space. These findings indicate that the permeability barrier is operative in adrenal tissue. The addition of synthetici β1-24 ACTH was shown to produce a significant increase in the d-xylose and 1-arabinose spaces in the adrenal preparations without causing any increase in the spaces of the corresponding optical isomers. Thus the proposal by Levine et al. concerning to the insulin action is compatible with the effect of synthetic ACTH on its target gland. The stereospecific effect on sugar transport was reproduced when cyclic AMP was added to the medium instead of synthetic ACTH. No effect of 5′-AMP was observed. Although prostaglandin E1 diminished the response of sugar permeability of rabbit adrenals to synthetic ACTH, the effect of cyclic AMP on sugar transport was uninfluenced by the addition of prostaglandin E1. It is quite possible from these data that β1-24 ACTH alters the sugar transport system in adrenal cortex by stimulating the formation of cyclic AMP. When bovine thyroid slices were incubated in the presence of a TSH preparation or cyclic AMP, there was also a stereospecific effect on sugar transport of the same type as observed in the rabbit adrenal preparations. When blood or tissue concentrations are compared among hormones, cyclic AMP and main metabolic intermediates, it is tempting to suggest that cyclic AMP acts as an amplifier of hormone actions rather than a simple transmitter. Blood concentrations of almost all peptide hormones are 10-10 molar range, while tissue concentrations of main metabolic intermediates such as glucose-6-P and ATP are 10-3-10-4 molar range. Cyclic AMP concentration in various tissues is just between the above two groups, varying with the absence or presence of hormones. The signal of hormones seems to be amplified markedly by fluctuations in cyclic AMP concentration in their target organs. Since serum insulin concentration is 10-10 molar range, it appears worthy to determine whether an amplifier may be involved in the mechanism of insulin action. The effects of various cyclic nucleotides on sugar transport in muscle preparations were examined. In intact rat diaphragms dibutyryl cyclic AMP did not increase the distribution space of 3-o-methylglucose. In frog sartorius muscles dibutyryl cyclic AMP and cyclic CMP caused a significant increase in 3-o-methylglucose space, but cyclic GMP, cyclic IMP and cyclic UMP had no such effect. It is noteworthy that there is an analogy in the chemical structure between adenine (6-amino purine) and cytosine (6-amino 2-oxypyrimidine). Cyclic AMP appears not to be involved in the permeability response to insulin, but the possibility remains that the insulin action is mediated by another amplifier containing a 6-amino derivative of the purine or pyrimidine base.
日本内分泌学会の論文

5 糖の膜透過に対するホルモン性調節

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