Effect of Antagonistic Albumin on Insulin-stimulated Intracellular Metabolic Pathways

Previous data on incorporation of glucose C-14 into glycogen by the rat diaphragm had suggested that this synthetic pathway was unaffected by the albumin-associated insulin antagonist. To test the hypothesis that only the transport functions of insulin were blocked by this antagonist, studies on two insulin-stimulated intracellular pathways independent of transport were carried out. The increase in tissue levels of the I form of glycogen synthetase seen with insulin was not affected by antagonistic albumin (human fraction V). The D form of glycogen synthetase was also unaffected. However, insulin-stimulated adenine-8-C-14 incorporation into RNA was completely abolished by this albumin. A nonantagonistic albumin (bovine fraction V) by itself increased RNA synthesis indicating that the inhibition of insulin-stimulated RNA synthesis was not a general property of the albumin molecule. The physical-chemical and metabolic characteristics of the albumin-associated antagonist are summarized and are considered to be incompatible with the postulated physiological role for this insulin antagonist.