Some Effects of Adrenal Cortical Steroids on Intermediary Metabolism

Thorn, George W.; Renold, Albert E.; Winegrad, Albert I.

doi:10.1136/bmj.2.5052.1009

Cited by 93 publications

(6 citation statements)

References 18 publications

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“…The administration of glucocorticoids causes a significant change on the metabolism of carbohydrates, which can lead to insulin resistance, hyperglycemia and glycosuria. One of the first well-elucidated effects of this drug was its role in increasing hepatic gluconeogenesis, which seems to be related to the inhibitory effects of glucocorticoids on the conversion of pyruvic acid to acetyl-coenzyme A, leading to an accumulation of pyruvic acid and resulting in glucose resynthesis [ 15 – 17 ]. Increased induction of enzymes related to gluconeogenesis, such as glucose-6-phosphatase, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase contribute to this effect [ 18 ].…”

Section: Methodsmentioning

confidence: 99%

Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes

Alessi

Oliveira

Schaan

et al. 2020

Diabetol Metab Syndr

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Background The disclosure in the media of a benefit with the use of dexamethasone in patients with COVID-19 infection sets precedents for self-medication and inappropriate use of corticosteroids. Methods This is a critical interpretive synthesis of the data available in the literature on the effects of the use of corticosteroids and the impact that their indiscriminate use may have on patients with diabetes. Reviews and observational and experimental studies published until June 18, 2020 were selected. Results Corticosteroids are substances derived from cholesterol metabolism that interfere with multiple aspects of glucose homeostasis. Interactions between corticoid receptors and target genes seem to be among the mechanisms responsible for the critical functions of glucocorticoids for survival and anti-inflammatory effects observed with these medications. Corticosteroids increase hepatic gluconeogenesis, reduce peripheral use of glucose and increase insulin levels. Previous studies have shown that glucocorticoids have a pro-adipogenic function, increasing deposition of abdominal fat, and lead to glucose intolerance and hypertriglyceridemia. In addition, these drugs play a role in controlling liver metabolism and can lead to the development of hepatic steatosis. Glucocorticoids reduce the recruitment of osteoblasts and increase the number of osteoclasts, which results in increased bone resorption and greater bone fragility. Moreover, these medications cause water and sodium retention and increase the response to circulating vasoconstrictors, which results in increased blood pressure levels. Chronic or high-dose use of corticosteroids can, by itself, lead to the onset of diabetes. For those who were already diagnosed with diabetes, studies show that chronic use of corticosteroids leads to a 94% higher risk of hospitalization due to diabetes complications. In addition to the direct effects on glycemic control, the effects on arterial pressure control, lipids and bone metabolism also have a potential for severe consequences in patients with diabetes. Conclusion Fear and uncertainty toward a potentially serious infection may lead people to self-medication and the inappropriate and abusive use of corticosteroids. More than ever, it is necessary for health professionals to be alert and able to predict damages related to the use of these drugs, which is the first step to minimize the potential damages to come.

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Section: Methodsmentioning

confidence: 99%

Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes

Alessi

Oliveira

Schaan

et al. 2020

Diabetol Metab Syndr

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“…This, in turn, re-* This work was supported in part by a grant from the Upjohn Company and in part by the Dallas Heart Association. (23,24), and glucagon (25, 26), may obscure a hepatic effect of insulin by the marked increase in hepatic glucose release which characterizes the action of these counterregulatory hormones (27)(28)(29)(30).…”

mentioning

confidence: 99%

“…Insulin should be administered in a manner which minimizes the counter-regulatory response to hypoglycemia. Profound hypoglycemia with its attendant release of epinephrine (21,22), adrenal cortical hormones (23,24), and glucagon (25,26), may obscure a hepatic effect of insulin by the marked increase in hepatic glucose release which characterizes the action of these counterregulatory hormones (27)(28)(29)(30).…”

mentioning

confidence: 99%

The Physiological Significance of the Secretion of Endogenous Insulin Into the Portal Circulation. Iii. Evidence for a Direct Immediate Effect of Insulin on the Balance of Glucose Across the Liver*†

Madison¹,

Combes²,

Adams³

et al. 1960

J. Clin. Invest.

104

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There is at present general agreement, based upon abundant in vitro and in tvvo experimental evidence, that insulin exerts an immediate and profound effect on glucose utilization by muscle and adipose tissue (1-5). On the other hand, a direct hepatic action of insulin is disclaimed by most investigators since innumerable studies both in vitro and in vivo have failed to demonstrate clearly a consistent and reproducible effect of insulin upon hepatic glucose metabolism (5-12).Recent observations from this laboratory suggested that the site (13) and the rate (14) of insulin administration are important factors in eliciting a hepatic effect. However, in these as in all previous in vivo studies (11,(15)(16)(17)(18)(19), the conclusions regarding the hepatic action of insulin were inferential, since the net balance of glucose across the liver was not ascertained by direct measurement.Any experiments designed to elucidate the effect of insulin on hepatic carbohydrate metabolism should fulfill the following prerequisites:1. Hepatic, in contrast to splanchnic, glucose metabolism should be measured. In view of the marked sensitivity of the extrahepatic splanchnic tissues to insulin (1-5, 11, 12), separation of the effects of insulin on these tissues from its effects on the liver is mandatory. This, in turn, re-* This work was supported in part by a grant from the Upjohn Company and in part by the Dallas Heart Association. (23,24), and glucagon (25, 26), may obscure a hepatic effect of insulin by the marked increase in hepatic glucose release which characterizes the action of these counterregulatory hormones (27)(28)(29)(30).The present experiments were designed to meet these prerequisites in the following manner. First, dogs with complete end-to-side portacaval shunts were studied. This operation completely separates the liver from the remainder of the splanchnic tissues and thereby permits the measurement of hepatic rather than splanchnic glucose metabolism. Second, measures were taken to minimize or prevent the counter-regulatory mechanisms to hypoglycemia. In one group of experiments, insulin was administered by slow infusion which produced a very gradual modest decline in arterial glucose concentration. In another group, the hypoglycemic stimulus was further reduced in magnitude and duration by administering glucose after insulin infusion had been started. Finally hypoglycemia was prevented by using diabetic dogs with fasting hyperglycemia. 507

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“…Table 1 Fig. 2A (11) 102&22 ( Diabetic Cushing's (5) 197 f 19 (5) The patients with Cushing's disease were a heterogeneous group. In particular 5 of the patients were diabetic as judged by an oral glucose tolerance test and another 4 had normal tolerance to oral glucose.…”

Section: Resultsmentioning

confidence: 99%

The Effect of Obesity and Cushing's Disease on the Incorporation of Glucose into Lipid and Esterification of Palmitate by Human Adipose Tissue

Wilson¹,

Galton

1972

Eur J Clin Investigation

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1. Rates of lipogenesis from glucose and palmitate have been measured in adipose tissue obtained from patients with obesity, diabetes, Cushing's disease and surgical controls. 2. Conversion of glucose into neutral lipid when expressed on the basis of tissue protein decreased in the following order: Cushing's patients, controls, obese patients. 3. A similar pattern of incorporation of T‐palmitate into neutral lipid was observed for the three groups of patients, except the differences were less marked. 4. Maximal activities of phosphofructokinase in adipose tissue are reduced in obesity (p< 0.05) and diabetics (p< 0.1) compared to surgical controls. 5. Five of the patients with Cushing's disease had an abnormal glucose tolerance test and showed a reduction in maximal activities of hexokinase (p< 0.05) in adipose tissue compared to the other four patients with Cushing's disease when expressed on a wet weight basis.

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Some Effects of Adrenal Cortical Steroids on Intermediary Metabolism

Abstract: The importance of the adrenal gland to the total economy of the individual was indicated by the classic description of Thomas Addison in 1855 and the subsequent experiments of Brown-Sdquard (1856

Cited by 93 publications

References 18 publications

Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes

Dexamethasone in the era of COVID-19: friend or foe? An essay on the effects of dexamethasone and the potential risks of its inadvertent use in patients with diabetes

The Physiological Significance of the Secretion of Endogenous Insulin Into the Portal Circulation. Iii. Evidence for a Direct Immediate Effect of Insulin on the Balance of Glucose Across the Liver*†

The Effect of Obesity and Cushing's Disease on the Incorporation of Glucose into Lipid and Esterification of Palmitate by Human Adipose Tissue

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