The metabolic alterations of free fatty acid (FFA) were studied in diabetes mellitus, clinical and experimental, hyperthyroidism, and von Gierke's disease. Emphasis was placed on the relationship between disturbances in carbohydrate metabolism and mobilizations of FFA.
Clinical study
1) In non-ketotic diabetic patients no statistical correlation was found between serum FFA and blood glucose, determined on the same fasting venous blood. It was deduced, therefore, that the fasting serum FFA did not necessarily reflex the severity of diabetes in these patients, assuming the fasting blood glucose to be a indicator the severity of diabetes. However, in two cases of severe diabetic acidosis, the levels of fasting FFA were extremely high, 2250 μEq/1 and 1470 μEq/1, respectively, and no decrease in those levels occurred following the glucose administration. Even in non-ketotic diabetics the responsiveness of serum FFA to the glucose loading was found to be lower than in normal controls.
2) In the patients with hyperthyroidism, or with von Gierke's disease, the levels of fasting FFA were markedly higher than in normal controls. Contrary to diabetes mellitus, the fasting FFA in these conditions was found to decrease more sharply following the glucose loading than in normal controls.
Expepimental study :
The control mechanism on serum FFA level is known to exert at the point of release from the adipose tissue. Isolated epididymal fat pads were employed for experimental studies on changes of FFA release in diabetes mellitus.
1) In alloxan diabetic rats there was a statistical correlation between the fasting blood glucose and the amount of FFA released in vitro from isolated fat pads in the absence of glucose in the incubation medium (γ= 0.634).
2) It was confirmed that the addition of glucose to the medium decreases the FFA mobilization from fat pads isolated from normal animals. The inhibitory effect of glucose was found to be diminshed parallel with the severity of diabetes in alloxan treated rats.
3) When the epididymal fat pads were isolated from alloxan diabetic rats without any manifest ketosis, and concentration of medium glucose was adjusted to the value of fasting blood glucose of each animal, the release of FFA was found to be almost of the same magnitude. This fact may constitute a possible basis of the clinical findings mentioned above that the values of serum FFA remains almost constant within the individual variations irrespective of a wide range in blood glucose. It is reasonable to presume that the release of FFA in the adipose tissue is suppressed and adjusted by hyperglycemia in non-ketotic diabetics. It seems to be one of the compensative actions of hyperglycemia in diabetes mellitus.
4) The inhibitory effects of glucose could not be demonstrated when epididymal fat pads of severe ketotic rats were employed. The addition of insulin to the medium or the previous administration of insulin to the rats was found to restore the inhibitory effect of glucose upon the release of FFA from the isolated fat pads.