Marvin L. Mitchell

GROWTH-HORMONE RELEASE BY GLUCAGON

Abstract Significant increments in serum-growth-hormone levels were found within 2-3 hours of subcutaneous administration of 1 mg. glucagon to both men and women. The response to glucagon corresponded to some extent to the decline in glucose but the values of growth hormone bore no relationship to the magnitude of the decrease. In view of its reliability, safety, and convenience, glucagon seems to be a valuable agent for the assessment of pituitary release of growth hormone.

Control of hypoglycemia with diazoxide and hormones.

Our interest in organic hypoglycemia stemmed from the need for an effective treatment of this disorder, particularly in patients no longer responsive to conventional measures. Although small doses of human growth hormone had been used with considerable success,1 the scarcity of the preparation precluded its application on a wide scale. Thus, faced with the problem of severe and recurrent episodes of hypoglycemia in a 76-year-old woman, our attention was directed to diazoxide, a hypotensive agent whose hyperglycemic properties had been noted previously during clinical trials.2 The patient, whose underlying disease was pancreatic islet cell carcinoma with metastases, was given several combinations of benzothiadiazines until symptoms were completely relieved. Normal blood sugar was obtained with the daily administration of 150 mg of diazoxide and 5 mg of bendr~flumethiazide.~ After five months of hospitalization, she was discharged and followed for an additional 19 months. During this time she required readmission three times. The information obtained during her hospitalization, plus data collected on a 55-year-old man with hypoglycemia secondary to an hemangiopericytoma, will serve as the basis for this discussion.

Use of Growth Hormone as a Diabetic Stimulus in Man

The diabetogenic potency of 10 mg. of human growth hormone and of 100 mg. of cortisone acetate was studied in five normal volunteers. Measurements of glucose, free fatty acids, immunoreactive insulin and immunoreactive growth hormone following a carbohydrate load revealed that twelve hours after a single intramuscular dose of growth hormone impairment of glucose tolerance and elevation in both serum insulin and free fatty acids were evident. Cortisone alone resulted in minimal changes in these indices, and the combination of cortisone and growth hormone was similar in effect to growth hormone alone. Concentrations of growth hormone in serum were still elevated twelve to fifteen hours after the intramuscular administration of a single 10 mg. dose.

Use of Enzyme Proteolysis for the Immunochemical Measurement of Insulin

An immunochemical assay has been designed that utilizes the catalytic properties of glutathione-activated ficin to separate antibody-bound radioinsulin from unbound insulin I-131. Both the recovery of human insulin added to serum and the failure to detect chemically inactivated insulin provide evidence for the precision and specificity of the procedure. Measurements of endogenous insulin in serum (diluted 1:10) made after the administration of glucose or tolbutamide revealed rapid increases in circulating levels of hormone in nondiabetic subjects. The successful application of enzyme hydrolysis as the basis of a reliable and rapid immunoassay for insulin suggests that with the appropriate antibody and labeled antigen, the same principle could be employed to measure concentrations of other hormones or substances that are potentially antigenic.

The Measurement of Insulin Binding By Resin Paper in Vitro

In a previous communication, mention was made of a method for measuring the protein-binding of insulin in serum by interacting serum containing insulin I-131 with a strip of resin paper and calculating the fraction of radioactive insulin adhering to the paper after the serum had been displaced by a buffer. Although specific values were not given in that report, the measurements of insulin-binding and of maximal insulin-binding capacities of serum were distinctly different in insulin-responsive and insulin-resistant diabetic patients. This technic, therefore, provided a simple and reliable means for rapid assessment of insulin binding in large numbers of serum samples, and for studying diabetic patients who require unusually high doses of insulin. The details of the resin paper technic and the results of the insulin-binding determinations are presented at this time.

Metabolism of thyroglobulin-I131 in the guinea pig in vivo and in vitro

Abstract Following the subcutaneous administration of a saline preparation of I 131 -labeled thyroglobulin (TG-I 131 ) to guinea pigs, plasma and tissues were found to contain iodide, monoiodotyrosine, diiodotyrosine and thyroxine. Comparisons of tissue: plasma ratios of total I 131 radioactivity revealed that the liver and kidney were the principal organs involved in the metabolism of the thyroglobulin. Four hours after the administration of thyroglobulin-I 131 , large concentrations of thyroxine-I 131 were obtained from liver and kidney, and by 24 hours the content of this hormone had increased appreciably in other organs. Incubation of thyroglobulin-I 131 with various tissue homogenates in vitro disclosed that the liver and kidney gave rise to the largest percentage of thyroxine-I 131 , while adrenal and testicle resulted in smaller but substantial yields of this hormone. Neither muscle nor plasma had any discernible effect upon the metabolism of thyroglobulin-I 131 when compared with the results obtained from the incubation of I 131 -labeled thyroglobulin in buffer alone.

Lack of dissociation between insulin and antibody from guinea pig.

Summary Studies assessed the extent to which insulin-131I and unlabeled insulin exchanged in antiserum from immunized guinea pigs. Comparisons of patterns of radioactivity obtained after agar gel electrophoresis of antiserum containing labeled and stable insulin, added in reversed sequences, revealed almost no exchange between insulin-131I and crystalline insulin.