Daily injection of a group of sheep with 75 mg. cortisol acetate (1.2 mg. per kilogram body weight) resulted in hyperglycemia and in a marked increase in plasma immunoreactive insulin concentrations. Doubling the dose of cortisol after fourteen days did not result in further increases in glucose or insulin concentrations, but the elevated levels were maintained throughout treatment. Intravenous glucose tolerance tests using 0.1 gm. glucose per kilogram body weight showed that the rate of glucose removal was decreased and the increment in plasma insulin concentration reduced by cortisol treatment. With a larger glucose load (0.5 gm. per kilogram body weight) there was an exaggerated insulin response to the increased plasma glucose level during the first period of cortisol treatment, but in the second period the response was no greater than that in the control period. Changes in plasma glucose and insulin concentrations in the eight hours following feeding were much exaggerated during cortisol treatment, even though there is little absorption of glucose from the digestive tract in this species.
In the absence of evidence of increased glucose turnover in the sheep during cortisol-induced hyperglycemia, the changes are indicative of marked impairment of peripheral glucose metabolism and antagonism of insulin action by cortisol in this species.