The Acute Effect of Hydrocortisone on Hepatic Glucose Output and Peripheral Glucose Utilization*

Abstract

There is abundant experimental evidence indicating that adrenal glucocorticoids have a profound effect on carbohydrate metabolism (1-9). Agreement is general that they accelerate hepatic gluconeogenesis and increase liver glycogen stores (5-9), but their action on peripheral glucose utilization is still unsettled (5,6,8). Although the effects of the chronic administration of glucocorticoids are well defined and changes in carbohydrate metabolism have been recorded as early as 2 to 4 hours (10-18) after adrenocorticoid administration, the precise time of onset of glucocorticoid-induced alterations in carbohydrate metabolism has not been established. An immediate action on glucose metabolism has not been demonstrated in vivo; indeed, recent studies have suggested that the effect of adrenocorticoids on carbohydrate metabolism is delayed for at least 2 hours, beginning at a time when steroid concentrations are decreasing (10,13, 14). The changes in glucose metabolism occurring in the earliest period after glucocorticoid administration are especially * Submitted for publication July 12, 1963; accepted October 17, 1963. This work was supported in part by a U. S. Public Health Service grant (A-4236) from the National Institute of Arthritis and Metabolic Diseases, Bethesda, Md., and by grants from the Upjohn Co., Kalamazoo, Mich., and Chas. Pfizer & Co., New York, N. Y.A preliminary report of this work has been published in abstract form (The paradoxical effect of hydrocortisone on hepatic glucose output. Clin. Res. 1961, 9, 29 important to define since obscuring secondary effects are less likely to be present.The purpose of the present study was 1) to delineate the earliest detectable change in carbohydrate metabolism after acute glucocorticoid administration, 2) to characterize the early effects of glucocorticoids on hepatic glucose output, and 3) to determine whether glucocorticoids alter peripheral glucose utilization. Changes in hepatic glucose output and peripheral glucose utilization were followed during the initial 90 to 120 minutes after the intravenous injection of cortisol in dogs with chronic end-to-side portacaval shunts. This preparation was chosen because it separates the liver from the extrahepatic splanchnic circulation and therefore permits measurement of hepatic rather than splanchnic glucose balance. From the changes in hepatic glucose output and arterial glucose concentration, changes in peripheral glucose utilization can be calculated (19). MethodsThirteen studies were done on dogs with complete endto-side portacaval shunts. At least 1 month was allowed for complete recovery from the operative procedure before experiments were performed. Stable weights were maintained in these animals by a diet, supplemented with vitamins, containing 5&% of the total calories as carbohydrate, 20 to 30% as protein, and the remainder as fat.Studies were performed after a 15-hour, overnight fast with Nembutal anesthesia (25 mg per kg). Hepatic venous samples were collected through a cardiac catheter inserted deep...

Glucose Production and Utilization in the Newborn Puppy

“…The HGP differs from net hepatic glucose output (NHGO) by the amount of glucose utilized by the liver, hepatic glucose utilization. MADISON et al [I41 have discussed at length the conditions under which HGP approximates NHGO and have demonstrated that in the fasting state there is a close correlation between the two variables [13].…”

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

“…increase of GC in response to acute stress leads to increased alertness, mobilization of glucose and fatty acids, and enhanced memory formation [14][15][16]. However, after chronic stress and long term elevations of GCs, the effects of GCs are detrimental with neurotoxic, immunosuppressive, and metabolic consequences [17][18][19].…”

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

“…7). sion of hepatic glucose release and insulin induced stimulation of glucose uptake [34,35]. In the absence of an appropriate compensatory increase in insulin secretion, both cause hyperglycaemia [12,13,25,36].…”