肝糖原に対するグルカゴンの晩期増量効果について
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概要
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Glu agon is known to cause a transient hyperglycemia by glycogenolysis in the liver. Liver glycogen immediately decreases after glucagon administration. On the contrary, some investigators has recently reported that the liver glycogen increased after more than 24 hours following injection of over medium doses of glucagon. On the other hand, a few studies have been published indicating that a negative balance of nitrogen occured by the administration of a large dose of glucagon. That is, the metabolic action of glucagon is similar to that of glucocorticoid. Therefore, it is reasonable to assume that glucagon causes a certain effect on gluconeogenesis. From the above mentioned stand-point, the mechanism of the delayed liver glycogen increase by glucagon was studied as follows. <BR>1. Liver glycogen production due to intraperitoneal injection of 2g/kg. of alanine to 24 hours fa sting rats definitely increased by the pre-treatment of 300γ/kg. of glucagon (intraperitoneal injection). This fact indicates that glucagon accelerates gluconeogenesis from alanine. <BR>2. The general pattern of metabolism in the acceleating condition of gluconeogenesis was investigated. In this case alloxan diabetic and hydrocortisone given animals were adopted as favourable materials for investigating. At first, alanine (200μM) was added as a substrate to the liver slices of these treated rats. After 1 hour's incubation at 37°C in Warburg flask, the formation of glucose, pyruvate or glycogen from alanine in vitro was found to be increased in the liver slices of treated rats fasted for 24 hours. Secondly, the liver transaminase (glutamic pyruvic- and glutamic oxaloacetic transaminase) was confirmed to be increased 3 to 7 fold, especially a pronounced rise of activity was noted in glutamic-pyruvic transaminase. <BR>3. The experiments were performed in the same may with glucagon and the same trend was confirmed. That is, the delayed increase of liver glycogen is concerned with the enhancement of gluconeogenesis, which is due to a rise of activity in liver transaminase. <BR>4. In order to elucidate whether such an accelerating effect of gluconeogenesis by glucagon depends on the adrenal cortex, 20γ/kg. body weight of glucagon was intravenously administered to human adults, and the urinary excretion of 17-OHCS were measured. Of total 8 cases, increased excretion of 17-OHCS were recognized in 6 cases. On the other hand, in adrenalectomized rats, daily injection of glucagon for 3 days did not promote the liver transaminase activity. <BR>Accordingly, it is concluded that glucagon causes the delayed liver glycogen increase mainly by way of the adrenal cortex.
- 一般社団法人 日本内分泌学会の論文