白鼠副睾丸脂肪組織の糖質並びに脂質代謝に関する研究
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Increased knowledge of metabolic disorder of adipose tissues in diabetes mellitus is presenting an important problem in the pathological physiology of diabetes. Stetten and Boxer (J. Biol. Chem., 156 : 271, 1944) studied the fat metabolism of diabetes using D<SUB>2</SUB>O and reported the possible inhibition of fat synthesis from glucose in diabetic animals, resulting in glycosuria caused by the unused glucose. The direct metabolic studies of the isolated adipose tissue thus makes an interesting problem.<BR>Studies were made on the behavior of glucose uptake and glycogen synthesis of the isolated diaphragm and liver slices of rats, and compared with those of epididymal adipose tissues with reference to normal and alloxan diabetic rats. Various hormones and antidiabetic drugs were also tested for their effect on the metabolism of isolated tissues excised from normal and diabetic rats. For the entire procedure, Warburg's apparatus was employed and the isolated tissues were incubated under ordinary experimental conditions, following the basic method previously described by Tsuji (Diabetes, Tokyo, 2 : 15, 1959.) and Waimatsu (will be published in Folia Endocrinologica Japonica). The results are summarized as follows : <BR>1) Cortisone and prednisolone showed definite inhibitive effects upon glucose uptake of the epididymal adipose tissues. This inhibition could not be overcome by insulin. Comparative studies on the diaphragm showed only a slight increase of glucose uptake ; those on the liver slices showed a decrease of glucose uptake both by pretreatment with cortisone or prednisolone.<BR>2) Pretreatment with ACTH gave decreased glucose uptake in the liver slices, but with the epididymal adipose tissues and diaphragm, both glucose uptake and insulin effect were found to be increased. As regards to epididymal adipose tissues it is assumed that ACTH can exert a direct lipolytic action, through which liberation of NEFA and increased glucose uptake could be induced. Similar effects on glucose uptake had been observed on pretreatment with growth hormone. After Waimatsu, however, in a certain pre-exhaustion state, the glucose uptake of epididymal adipose tissues seems to be accelerated. These variable glucose uptakes of epididymal adipose tissues seem to indicate that glucose uptake of this particular tissue is generally increased in the physiological conditions, when accompanied with moderate fat consumption.<BR>3) Gonadotropin, androgen and estrogen were not capable of inducing appreciable metabolic changes of epididymal adipose tissues.<BR>4) Isolated tissues of alloxan diabetic rats, in general, showed decreased glucose uptake, especially with the epididymal adipose tissues, but the insulin effect in vitro was markedly increased. This phenomenon implies the relatively easy restoration of the disturbed carbohydrate metabolism of experimental diabetic animals. Comparative therapeutic studies with insulin, D860 and DBI disclosed almost identical therapeutic effects with insulin and D860, where as DBI induced a decrease of glucose uptake after a long-term administration.<BR>5) Formation and liberation of NEFA in and from the epididymal adipose tissues of alloxan diabetic rats showed an increase in proportion to the decreased glucose uptake. These metabolic disturbances of epididymal adipose tissues could be restored more or less by addition of glucose alone or glucose plus insulin to the incubation medium or through pretreatment of diabetic rats with insulin or D860. Addition of ACTH or hydrocortisone to the incubation medium invited further inhibition of glucose uptake and more liberation of NEFA possibly through the disturbance of fat synthesis. Metabolic behavior similar to this tendency was observed also in vivo experiments. Comparison of metabolic effects of insulin and D860 showed almost no difference in the above experiments.
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