Daily changes in concentration of pancreatic and serum insulin and of blood glucose during 5 days of treatment of rats with growth hormone, ACTH, cortisol, dexamethasone, and tolbutamide alone and in combinations.

Rats with or without 0.5% tolbutamide in the diet were iniected over a 5-day period with growth hormone, ACTH, cortisol, dexamethasone, or various mixtures of these diabetogenic hormones and the daily alterations in blood glucose (BG), serum (Sl), and pancreatic insulin (PI) concentrations followed as well as glucosuria. GH (5 mg/day) increased the insulin concentration in the pancreas and serum without affecting blood glucose. ACTH (80 IU/day) decreased PI and increased 51 with only a slight increase in BG. Cortisol and dexamethasone decreased PI and increased 51 and BG. The severalfold increase in 51 with glucocorticoids always preceded the increase in 80 by 12-24 hr. Mixtures of GH with the glucocorticoids increased and quickened the rise in BG and 51 and the falls in PI, but the rise in SI always preceded the rise in BG by several hours. During multiple hormonal treatment, PI decreased in magnitude usually for 34 days but by the fifth day tended to revert toward normal, showing adaptation. In contrast, BG and 51 tended to remain elevated and glucosuria persisted. These data suggest that in spite of the high concentrations of diabetogenic agents used compensatory changes were made by the rat with intact pancreas over a period of 5 or more days. This hormonally induced condition of elevated 51 and BG but normal PI is characteristic of insulin resistance. Tolbutamide by itself decreased PI without a rise in SI (except for a temporary increase at 4-8 hr after the first injection) and with only a minor decrease in BG. Most of the changes due to the hormones were accentuated in rats with 0.5% tolbutamide in the diet, suggesting that tolbutamide is diabetogenic because it decreases PI.