Robert W. Bates

Decreased binding of insulin to its receptors in rats with hormone induced insulin resistance

Abstract Insulin and glucagon receptor binding was studied in purified liver membranes from rats made insulin resistant by implantation of an MtT pituitary tumor which secretes growth hormone, prolactin, and ACTH. Insulin binding to its receptors was decreased and correlated with the degree of insulin resistance. In contrast, binding of glucagon to its receptors was unchanged.

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

Abstract Rats with or without 0.5% tolbutamide in the diet were injected 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 (SI), 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 SI with only a slight increase in BG. Cortisol and dexamethasone decreased PI and increased SI and BG. The severalfold increase in SI with glucocorticoids always preceded the increase in BG by 12–24 hr. Mixtures of GH with the glucocorticoids increased and quickened the rise in BG and SI 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 3–4 days but by the fifth day tended to revert toward normal, showing adaptation. In contrast, BG and SI 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 SI 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.

A Method for Assay of Insulin Using Alloxan Diabetic Hypophysectomized Mouse

Summary Two methods for the assay of small amounts of insulin are presented. Both involve using the alloxan diabetic hypophysectomized mouse. One involves measuring the fall in blood sugar in test animals over a 20 minute period after the intravenous administration of insulin, the insulin being given one hour after the subcutaneous injection of 25 mg glucose. The other method involves measuring the fall in blood sugar 30 minutes after the intraperitoneal administration of the insulin, which, as in the intravenous method, is given one hour after a 25 mg glucose meal. The intravenous method, which is the more sensitive of the two, is capable of detecting as little as 250 μU of insulin.

Species Difference in Hormonal Control of Intestinal Weight and Food Intake of Rats and Pigeons

Summary In rats voluntary daily food intake per 100 g body weight varied by a factor of 4-fold, from 4 g in rats with mammotropic tumors (MtT) on a high fat diet to 15 g of regular rat chow in 80% pancreatectomized rats with MtT and diabetes. The weight of the empty intestine per 100 g body weight varied proportionally and was independent of the high blood levels of pituitary hormones from MtT. The empty intestinal weight was roughly one-half of the weight of the daily food intake in all rats whether partially pancreatectomized, adrenalectomized, diabetic or normal. In pigeons the intestinal weight is not changed much in weight by merely altering food intake, and its weight is nearly doubled by injections of 1 to 5 mg of growth hormone or prolactin daily or equivalent without change in food intake. No explanation other than species difference for these results is possible from the current data. These experiments suggest that food intake data studies are a necessary supplement to intestinal weight studies.