Influence of Cortisol on Plasma Insulin in the Sheep

Abstract

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. DIABETES 76:566-71, August, 1967. Since the observation by Long, Katzin, and Fry 1 that the blood glucose concentration of normal or partially depancreatized rats was increased by treatment with adrenal steroids, effects of the glucocorticoid hormones on carbohydrate metabolism and on pancreatic islet cell morphology have been widely studied. The work in these fields has recently been reviewed in detail by Haist. 2 However, while changes in the islets suggest increased insulin secretion, 3 the effects of glucocorticoid hormones on peripheral plasma insulin concentrations have received little attention.In the sheep, hyperglycemia usually accompanies elevated plasma cortisol concentrations, 4 ' 6 but despite this positive association between glucose and cortisol concentrations we have obtained no evidence to suggest that the hyperglycemia is maintained by high rates of glucose production. 6 In view of the changes in pancreatic islet size and structure which occur during hyperadrenocorticism in other species, 3 * 7 " 9 it seemed likely that plasma insulin concentration in the sheep would be influenced markedly by cortisol treatment. The observations reported here show that plasma insulin concentration increases during the hyperglycemia produced by cortisol treatment and the results give added support to the view that cortisol seriously antagonizes peripheral glucose metabolism. MATERIALS AND METHODSEight adult Border Leicester x Merino crossbred female sheep (body weight 62.5 db 1.3 kg.), thoroughly trained to the procedures involved, were used in the experiments. They were housed individually in pens and were fed 8po gm. daily of a diet consisting of equal parts of chaffed lucerne...

Dietary Regulation of Plasma Insulin and Growth Hormone Concentrations in Sheep

“…As the plasma concentrations of glucose fell in a narrow range, the plasma insulin concentration could not be shown to depend on plasma glucose concentrations, even though there is evidence that increases in the glucose concentration increase insulin secretion in sheep (Boda 1964;Bassett and Wallace 1967;Horino et al 1968). Since infusion of either propionic or butyric acids into the peripheral or portal circulation also stimulates insulin secretion in sheep Manns, Boda, and Willes 1967;Horino et al 1968), it has been postulated that these acids are important stimuli to insulin secretion.…”

“…The concentration of insulin in plasma was measured by radio-immunoassay using either a double-antibody method (Hales and Randle 1963) as modified by Bassett and Wallace (1966) or a method using an adsorbent, talc, to separate free [125IJinsulin from antibody-bound labelled hormone (Rosselin et al 1966); the procedure is described by Bassett and Thorburn (1971).…”

Lipid Disorders in Renal Transplant Recipients

“…Steroids, increasing basal insulin level [14,15], could stimulate he patic triglyceride production [16,17] or alter natively they could impair removal of tri glyceride elevation [18]. Another possible in volvement of corticosteroids in the genesis of hypercholesterolemia is suggested by the find ing in rats that the administration of cortisone stimulates hepatic lipoprotein production and raises plasma cholesterol levels [16].…”

Growth as affected by general hormonal factors and hormonal balances, and the limitations of such studies

“…Thyroidectomy after birth also retards the growth of lambs (Falconer and Draper, 1968) (Spurlock and Clegg, 1962 ;Clark et al, 1963 ;Carroll et al, 1963 in bull calves). This increase in adiposity could be due to hyperglycemia and hyperinsulinemia caused by the injections (Bassett and Wallace, 1967 ;Bassett, 1968).…”