Samuel Soskin

Relationship Between Sugar Concentration and Glycogenetic Action of Insulin on Rat Diaphragm in vitro

Summary Glycogen deposition in rat diaphragm in vitro varies directly with the concentration of glucose in the medium. Insulin catalyzes this process greatly at low sugar concentrations but very little at high concentrations. The bearing of these results on the mechanism of insulin action is briefly discussed.

Mechanism of Estrogen Effect on Nasal Mucosa in Atrophic Rhinitis; Successful Treatment with Prostigmin

Periodic changes in the appearance of the nasal mucosa during the menstrual cycle, have long been recognized. A consideration of this so-called “naso-sexual relationship” led Mortimer, Wright and Collip 1 to observe the effects of parenterally administered estrogenic substance upon the mucous membranes of the nose. The changes which they observed suggested the use of estrogens in the treatment of atrophic rhinitis. They reported clinical improvement in such cases, following the repeated application of oily solutions of estrone directly to the nasal mucous membranes. Blaisdell 2 arrived at the same therapeutic idea from the similarity in the pathology of atrophic rhinitis and of atrophic or senile vaginitis, and from the previously reported efficacy of local estrogen therapy in the latter condition. He also reported clinical improvement in atrophic rhinitis obtained by intranasal estrin therapy. The local treatment of atrophic rhinitis with estrone has produced only mildly favorable or negative results in our hands. We were also impressed by the lack of any evidence of gonadal deficiency in most of our cases. Both these facts deprecated the importance of the “naso-sexual relationship”, but did not offer any other explanation for such therapeutic results as were obtained with the estrogens. The situation was clarified by a recent study of one of us and coworkers, 3 in which it was found that the various component phenomena of estrus may be classified into 2 categories: 1. The specific proliferative effects of estrin, and 2. Those effects which are secondary to hyperemia. The latter effects can be reproduced by non-specific hyperemic agents such as yohimbin. However, when they result from estrin action, they are due to the acetylcholine-liberating properties of this hormone, as demonstrated by Reynolds. 4

Use and Abuse of the Dextrose Tolerance Test

The dextrose tolerance test is commonly misinterpreted as an index of the ability to oxidize carbohydrate. This misinterpretation and the fact that the test dose of sugar is usually administered by the oral route render the test practically worthless. Actually, the test is chiefly an index of the efficiency of blood sugar regulation by the liver, under the influence of various endocrine glands. Thus interpreted and done intravenously, it can yield useful information.

Effect of Added Glucose on Rate of Appearance of Free Sugar in Liver Brei

Summary and Conclusions It is concluded that the inhibition of the rate of appearance of free sugar in glycogenolyzing liver brei, probably depends upon an inhibition of the first step in glyco-genolysis, namely, the phosphorylosis of glycogen to glucose-1-mono-phosphate. These results confirm the previously postulated intrinsic hepatic homeostatic mechanism which contributes to blood sugar regulation by determining the rate of sugar output by the liver. Since it occurs in vitro, the non-essential nature of extra insulin secretion for this regulatory activity is confirmed. 3 The actual relationship of insulin and other hormones to this mechanism has already been indicated.

Validity of Chemical Balance Studies in Eviscerated Animals, as Index of Carbohydrate Utilization

Discussion and Summary It is clear that neither of the possible objections to our previous method of calculating carbohydrate utilization is sufficiently valid to materially affect the end results. That is, the amounts of free sugar, higher carbohydrate intermediates, or lactic acid present in the muscles are not such as to invalidate calculations based on blood sugar and lactic acid values, and distribution ratios. This agrees with the earlier, basic work of Best, Dale, Hoet and Marks, 9 who demonstrated that the sugar which disappeared from the blood of eviscerated spinal cats was equal to the sum of the glycogen deposited in the muscles and the glucose equivalent of the oxygen consumed.

Effect of Insulin on Rate of Appearance of Free Sugar in Liver Brei

Summary Insulin inhibits glycogenolysis in the liver, and reinforces the inhibitory effect of added dextrose.

Possible Physiologic Significance of the Zinc Content of Insulin

It is known that the effectiveness of insulin in lowering the blood sugar level is dependent upon the integrity of the S-S groups which form part of its protein structure. 1 This suggested the possibility that insulin might exert its physiologic action through the influence of its S-S groups upon such tissue enzymes as are dependent upon S-H groups for their activity. 2-5 We therefore studied the in vitro effect of insulin upon succino-oxidase activity. A significant effect was found. But, it soon became apparent that this in vitro action of insulin did not depend upon its S-S groups, but rather upon its zinc content. Methods and Results. An active succino-oxidase preparation was obtained from minced, fresh beef heart. Its activity was determined by measuring the oxygen consumption in the presence of excess succinate in the Warburg apparatus (38°C; gas phase—air; pH 7.4). Table I presents a typical experiment of a large number which consistently showed a significant inhibition of the succino-oxidase system by crystalline insulin.†

Reduced Glutathione of Tissues and Insulin Sensitivity

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

Acid-Base Balance and the Distribution of Fat in the Blood

Conclusions 1. A reciprocal relationship has been shown to exist between the carbon dioxide combining power of the blood and the concentration of total fat in the blood serum. 2. Changes in serum fat content produced by altering the acid-base balance are not accompanied by changes in the fat content of the whole blood, within the duration of our acute experiments. 3. The changes in serum fat are therefore the result of a shift of fat between the red blood cells and the blood plasma. 4. The significance of serum and whole blood lipemias as regards fat transport, is discussed.

Cyclic Inhibitory Influence of the Rat's Ovary on the Uterine Response to Estrin

Discussion and Summary We have demonstrated the existence of an ovarian factor in the rat, which inhibits the uterine response to estrin, and which operates in a cyclic manner corresponding to the estrus cycle of the animal. Although the development of uterine inhibition during the cycle is paralleled by the development of corpora lutea in the ovary, we do not believe that the inhibition is due to progestin. This conclusion is based on evidence that progestin, in amounts sufficient to inhibit the effects of estrin on the uterus, always results in progestational phenomena in this organ. 2 , 3 , 4 But, at no time in the present or previous 1 work did we observe progestational changes in the uterus. Furthermore, the antagonism between progestin and estrin also includes the inhibition of vaginal cornification, 2 , 3 while in our work the vaginal mucosa never failed to become cornified after estrin administration.