Endocrinologic and metabolic effects of interleukin-6 in humans

1995 ◽  
Vol 268 (5) ◽  
pp. E813-E819 ◽  
Author(s):  
J. M. Stouthard ◽  
J. A. Romijn ◽  
T. Van der Poll ◽  
E. Endert ◽  
S. Klein ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Interleukin 6 ◽  
Cell Cancer ◽  
Metabolic Effects ◽  
Isotope Dilution Method ◽  
Saline Control ◽  
Dilution Method ◽  
Plasma Norepinephrine ◽  
Metabolic Clearance

Interleukin-6 (IL-6) is one of the major circulating cytokines in catabolic states. To investigate its endocrinologic and metabolic actions in vivo, we studied eight patients with metastatic renal cell cancer two times, once during infusion of saline (control) and once during a 4-h infusion of 150 micrograms recombinant human IL-6 (rhIL-6). Rates of appearance (Ra) of glucose and free fatty acids (FFA) in plasma were measured by using the isotope dilution method. Energy expenditure and substrate oxidation were determined by indirect calorimetry. rhIL-6 induced increases in plasma norepinephrine (+261 +/- 97%, P < 0.001), cortisol (+210 +/- 48%, P < 0.001), and glucagon (+70 +/- 18%, P < 0.001), in resting energy expenditure (+25 +/- 2%, P < 0.001 vs. control), and in plasma FFA concentration (+60 +/- 30%, P < 0.001), FFA Ra (+105 +/- 18%, P < 0.001), and fat oxidation (+38 +/- 16%, P < 0.001). Glucose Ra increased by 20 +/- 5% (P < 0.01) during rhIL-6 infusion with a concomitant increase in the metabolic clearance rate of glucose. In conclusion, our data demonstrate that rhIL-6 induces many of the endocrinologic and metabolic changes found in catabolic states and thus may mediate some of the metabolic effects previously ascribed to other cytokines.

Demonstration of in vivo metabolic effects of 3,5-di-iodothyronine

1996 ◽  
Vol 149 (2) ◽  
pp. 319-325 ◽  
Author(s):  
M Cimmino ◽  
F Mion ◽  
F Goglia ◽  
Y Minaire ◽  
A Géloën
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Octanoic Acid ◽  
Control Level ◽  
Metabolic Effects ◽  
Daily Energy Expenditure ◽  
Sprague Dawley ◽  
Daily Energy ◽  
And Control

Abstract The objective of the present study was to test in vivo the metabolic effects of 3,5-di-iodothyronine (3,5-T2) in unanesthetized and unrestrained male Sprague–Dawley rats. Amino acid and lipid metabolisms were investigated by breath tests using as tracers the 13C-carboxyl-labeled molecules of leucine, α-ketoisocaproic acid (KIC) and octanoic acid, in four different groups of rats: hypothyroid animals (receiving propylthiouracil (PTU) and iopanoic acid), hypothyroid animals treated with either a daily i.p. injection of 3,5-T2 (25 μg/100 g body weight), or triiodothyronine (T3) (1 μg/100 g body weight), and control euthyroid animals receiving equivalent volumes of the vehicle solutions. Energy expenditure was measured by continuous monitoring of O2 consumption and CO2 production in these different groups. Daily energy expenditure was decreased by 30% in PTU-treated rats. The chronic treatments with 3,5-T2 and T3 restored daily energy expenditure to the control level. 13CO2 recovered in breath following the i.v. injection of octanoic acid-[1-13C] was decreased in hypothyroid animals compared with control animals (P<0·05) and restored to control values by T3 and 3,5-T2 treatments. The 13CO2 recovered in breath after i.v. injection of leucine-[1-13C]was increased in PTU-treated compared with control animals (P<0·05). Chronic treatment with either 3,5-T2 or T3 restored 13CO2 to control values. Excretion of 13CO2 recovered in breath following the i.v. injection of KIC-[1-13C] was increased in PTU-treated compared with control animals. Chronic treatments with either 3,5-T2 or T3 did not restore KIC decarboxylation. These results suggest that 3,5-T2 exerts metabolic effects on energy expendi ture, on both lipid β-oxidation and leucine metabolism in hypothyroid rats. We conclude that 3,5-T2 is a metabolically active iodothyronine. Journal of Endocrinology (1996) 149, 319–325

Effect of glucocorticoids on renal net glucose release in vivo in normal and diabetic rats

1983 ◽  
Vol 245 (2) ◽  
pp. F223-F226
Author(s):  
F. Kamiya ◽  
H. Kimura ◽  
T. Takeuchi ◽  
K. Kida ◽  
H. Nakagawa
Keyword(s):  
Blood Glucose ◽  
Normal Control ◽  
Isotope Dilution ◽  
Diabetic Rats ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Glucose Release ◽  
Streptozotocin Induced Diabetes ◽  
Adrenalectomized Rats

The effect of glucocorticoids on renal net glucose release in vivo in normal and diabetic rats was studied by the isotope-dilution method. Administration of hydrocortisone to normal fed rats increased renal net glucose release from 0.93 +/- 0.25 to 2.27 +/- 0.21 mg . dl-1 . min-1 and increased its contribution to blood glucose from 27.0 +/- 4.5 to 46.6 +/- 4.0%. The renal net glucose release and its contribution to blood glucose in adrenalectomized rats were 0.40 +/- 0.06 mg . dl-1 . min-1 and 16.3 +/- 1.4%, respectively, significantly less than those of normal control rats, and these parameters were raised to the levels of normal control rats by the administration of hydrocortisone. In rats with streptozotocin-induced diabetes, the renal net glucose release and its contribution to blood glucose were significantly increased to 2.22 +/- 0.51 mg . dl-1 . min-1 and 46.7 +/- 4.9%, respectively, and these parameters were normalized by adrenalectomy. These data indicate that glucocorticoids play an important role in regulation of renal net glucose release and its contribution to blood glucose in both normal and diabetic rats.

Interferon-γ has immunomodulatory effects with minor endocrine and metabolic effects in humans

1999 ◽  
Vol 86 (2) ◽  
pp. 517-522 ◽  
Author(s):  
J. de Metz ◽  
F. Sprangers ◽  
E. Endert ◽  
M. T. Ackermans ◽  
I. J. M. ten Berge ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Controlled Trial ◽  
Plasma Concentrations ◽  
Resting Energy Expenditure ◽  
Interferon Γ ◽  
Metabolic Effects ◽  
Metabolic Systems ◽  
Ifn Γ ◽  
Resting Energy

To evaluate whether interferon-γ (IFN-γ) is involved in the interaction between the immune and endocrine systems in vivo, we studied six healthy subjects twice in a placebo-controlled trial: once after administration of recombinant human IFN-γ and, on another occasion, after administration of saline. The rate of appearance of glucose was determined by infusion of [6,6-2H2]glucose and resting energy expenditure by indirect calorimetry. Human leukocyte antigen-DR gene expression on monocytes and serum neopterin increased after administration of IFN-γ ( P < 0.05 vs. control). IFN-γ increased serum interleukin-6 levels significantly. Levels of tumor necrosis factor-α remained below detection limits. IFN-γ increased plasma concentrations of ACTH and cortisol ( P < 0.05 vs. control), IFN-γ did not alter concentrations of growth hormone, (nor)epinephrine, insulin, C peptide, glucagon, or insulin-like growth factor I. IFN-γ did not alter plasma concentrations of glucose and free fatty acids nor the rate of appearance of glucose. IFN-γ increased resting energy expenditure significantly. We conclude that IFN-γ is a minor stimulator of the endocrine and metabolic pathways. Therefore, IFN-γ by itself is probably not a major mediator in the interaction between the immune and the endocrine and metabolic systems.

Interleukin-6 Stimulates Coagulation, not Fibrinolysis, in Humans

1996 ◽  
Vol 76 (05) ◽  
pp. 738-742 ◽  
Author(s):  
Jacqueline M L Stouthard ◽  
Marcel Levi ◽  
C Erik Hack ◽  
Cees H N Veenhof ◽  
Hans A Romijn ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Plasma Levels ◽  
Antithrombin Iii ◽  
Cell Cancer ◽  
Saline Control ◽  
Severe Inflammation ◽  
Control Study ◽  
Prothrombin Activation ◽  
Coagulation And Fibrinolysis

SummaryThe role of IL-6 as a mediator of haemostatic changes during severe inflammation is controversial. To assess the effect of IL-6 on haemostasis we conducted a controlled cross-over study in eight patients with metastatic renal cell cancer. In all subjects coagulation and fibrinolysis were monitored during and after a 4-h infusion of either 150 μg recombinant human (rh) IL-6, or during infusion of saline (control study). Mean maximum IL-6 concentrations were 1418.0 ± 755.8 pg/ml. Compared to the control study, rhIL-6 induced activation of coagulation as reflected by a 190 ± 55% increase in the plasma levels of thrombin-antithrombin III complexes (p <0.001) and by a 24 ± 11% increase in the plasma levels of in the prothrombin activation fragment F1 + 2 (p <0.001). In contrast, fibrinolysis was not affected. We conclude that in severe inflammation IL-6 may contribute to the activation of coagulation, whereas other factors mediate changes in fibrinolysis.

scholarly journals Glycolaldehyde is an endogenous source of lysine N-pyrrolation

2020 ◽  
Vol 295 (22) ◽  
pp. 7697-7709 ◽  
Author(s):  
Miho Chikazawa ◽  
Jun Yoshitake ◽  
Sei-Young Lim ◽  
Shiori Iwata ◽  
Lumi Negishi ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Chemical Properties ◽  
Density Lipoprotein ◽  
Covalent Modification ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Stable Isotope Dilution ◽  
Modified Proteins

Lysine N-pyrrolation converts lysine residues to Nϵ-pyrrole-l-lysine (pyrK) in a covalent modification reaction that significantly affects the chemical properties of proteins, causing them to mimic DNA. pyrK in proteins has been detected in vivo, indicating that pyrrolation occurs as an endogenous reaction. However, the source of pyrK remains unknown. In this study, on the basis of our observation in vitro that pyrK is present in oxidized low-density lipoprotein and in modified proteins with oxidized polyunsaturated fatty acids, we used LC–electrospray ionization–MS/MS coupled with a stable isotope dilution method to perform activity-guided separation of active molecules in oxidized lipids and identified glycolaldehyde (GA) as a pyrK source. The results from mechanistic experiments to study GA-mediated lysine N-pyrrolation suggested that the reactions might include GA oxidation, generating the dialdehyde glyoxal, followed by condensation reactions of lysine amino groups with GA and glyoxal. We also studied the functional significance of GA-mediated lysine N-pyrrolation in proteins and found that GA-modified proteins are recognized by apolipoprotein E, a binding target of pyrrolated proteins. Moreover, GA-modified proteins triggered an immune response to pyrrolated proteins, and monoclonal antibodies generated from mice immunized with GA-modified proteins specifically recognized pyrrolated proteins. These findings reveal that GA is an endogenous source of DNA-mimicking pyrrolated proteins and may provide mechanistic insights relevant for innate and autoimmune responses associated with glucose metabolism and oxidative stress.

Leptin increases energy expenditure and selectively promotes fat metabolism in ob/ob mice

1997 ◽  
Vol 272 (4) ◽  
pp. R1204-R1209 ◽  
Author(s):  
J. J. Hwa ◽  
A. B. Fawzi ◽  
M. P. Graziano ◽  
L. Ghibaudi ◽  
P. Williams ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Energy Utilization ◽  
Metabolic Effects ◽  
Diurnal Fluctuation ◽  
Light Cycle ◽  
Intraperitoneal Dose ◽  
Circadian Fluctuation ◽  
In Vivo Analysis

Obesity occurs whenever energy intake exceeds energy expenditure. The ob gene product leptin is a potent anorectic agent when administered to ob/ob mice, but its effects on energy expenditure have not been investigated in detail. The present study was designed to analyze the acute metabolic effects of leptin in vivo. Analysis of oxygen consumption in ob/ob mice demonstrated a reduction in energy expenditure compared with lean controls; this reduction showed a diurnal fluctuation and was most evident during the light cycle. A single intraperitoneal dose of leptin increased oxygen consumption during the light cycle in ob/ob mice, ablating the circadian fluctuation in this parameter. In addition, leptin had a profound effect on fuel selection: the respiratory quotient was markedly reduced, indicating a reduction in carbohydrate oxidation and an increase in fat oxidation. These acute effects of leptin on metabolic parameters are consistent with the selective loss of body fat observed on chronic leptin treatment and suggest that increased energy utilization plays an important role in the anti-obese actions of leptin.

Norepinephrine: hormone and neurotransmitter in man.

1978 ◽  
Vol 234 (3) ◽  
pp. E252 ◽  
Author(s):  
A B Silverberg ◽  
S D Shah ◽  
M W Haymond ◽  
P E Cryer
Keyword(s):  
Acute Illness ◽  
Metabolic Effects ◽  
Plasma Norepinephrine ◽  
Metabolic Clearance ◽  
Half Time ◽  
Metabolic Clearance Rate ◽  
Norepinephrine Concentration ◽  
Basal Plasma ◽  
The Mean ◽  
Beta Hydroxybutyrate

To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function.

Pregnancy does not alter the metabolic clearance of 1,25-dihydroxyvitamin D in rats

1990 ◽  
Vol 258 (1) ◽  
pp. E158-E162 ◽  
Author(s):  
S. K. Paulson ◽  
K. K. Ford ◽  
C. B. Langman
Keyword(s):  
Clearance Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Female Rats ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Metabolic Clearance ◽  
Pregnant Rats ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Increased circulating levels of 1,25-dihydroxyvitamin D [1,25(OH)2D] during pregnancy could be due to an increase in production or decrease in the metabolic clearance rate of 1,25(OH)2D. To answer this question an isotope dilution method was used to determine the clearance rate of 1,25(OH)2D in pregnant and aged-matched nonpregnant female rats. A bolus of 0.146 muCi 1,25(OH)2[3H]D3 was given to 60 pregnant and 60 aged-matched nonpregnant rats and the disappearance of the isotope was followed in these animals over the next 48 h. In 12 pregnant rats vs. 14 nonpregnant controls not injected with tracer, plasma calcium (9.6 +/- 0.41 vs. 10.7 +/- 0.17 mg/ml) and 25(OH)D (17.1 +/- 1.15 vs. 25.4 +/- 1.58 ng/ml) levels were significantly lower (P less than 0.01 and P less than 0.001), whereas plasma 1,25(OH)2D levels (110 +/- 16.1 pg/ml vs. 77 +/- 6.0 pg/ml) were significantly higher (P less than 0.05). Clearance rates of 1,25(OH)2D of 25.8 +/- 1.31 microliters/min in pregnant rats and 20.2 20.2 +/- 1.38 microliters/min in nonpregnant aged-matched rats were not significantly different. Similarly, the apparent volume of distribution of 1,25(OH)2D in the pregnant rats (15 +/- 1.0 ml) was not significantly different from that in the nonpregnant control animals (18 +/- 2.1 ml). Production rates of.1,25(OH)2D were elevated in the pregnant rats (2.83 pg/min) compared with the nonpregnant controls (1.55 pg/min). In conclusion, the elevated maternal plasma 1,25(OH)2D level during pregnancy is a result of increased production and is not due to a decreased clearance.

ON THE VALUE OF SOME PARAMETERS OF ADRENOCORTICAL GLUCOCORTICOID FUNCTION

1963 ◽  
Vol 44 (4) ◽  
pp. 499-504 ◽  
Author(s):  
M. Van Der Straeten ◽  
A. Vermeulen ◽  
N. Orie ◽  
P. Regniers
Keyword(s):  
Urinary Excretion ◽  
Adrenal Cortex ◽  
Isotope Dilution ◽  
Isotope Dilution Method ◽  
Dilution Method ◽  
Steroid Excretion ◽  
Colorimetric Methods

ABSTRACT The authors studied the correlation between cortisol production, as measured by an isotope dilution method, and the urinary excretion of total and free Porter-Silber chromogens, as well as of 17-ketogenic steroids. Although a significant correlation exists between total Porter-Silber chromogens, 17-ketogenic steroid excretion and cortisol production, discrepancies are occasionally observed. Hence, different colorimetric methods should be used to assess the glucocorticoid activity of the adrenal cortex.

Sign in / Sign up

Export Citation Format

Share Document