Reduced Glutathione of Tissues and Insulin Sensitivity

Abstract

The sensitivity of an animal to insulin is usually judged by the extent and duration of the depression of the blood sugar level after the administration of insulin. The factors which are usually considered to exert an important influence upon the insulin depression curve are: the available carbohydrate stores in the liver and the ease with which these stores may be mobilized. 1 The state of the endocrine glands is important in both these respects, and it is well known that adrenalectomy, 2 hypophysectomy, 3 and thyroidectomy 4 increase the sensitivity to insulin. Another important factor in insulin sensitivity, to which less attention has been paid, is the rate of destruction or inactivation of insulin by the tissues of the body. That this factor is significant is shown by the well-established fact that the same amount of insulin becomes more effective when administered in divided doses or by prolonged constant injection than when given in a single dose. 5

The exact mode of insulin inactivation in the body is unknown, but ever since it was shown that insulin is a protein, the supposition has been that it is destroyed by proteolytic enzyme systems. 6 However, it is also known that the physiological action of insulin depends upon the integrity of its S-S groups, 7 , 8 and that the in vitro reduction of these groups by sulphydryl compounds renders the insulin inert upon subsequent injection. 9-13 That a similar mode of inactivation applies to insulin in the living organism is indicated by the work of Jacobs, who has recently demonstrated that the administration of cysteine decreases the reaction to subsequently injected insulin. 14