Effects of variation of the tri-iodothyronine/reverse triiodothyronine ratio in vivo on the metabolic characteristics of subsequently isolated hepatocytes

1987 ◽  
Vol 72 (4) ◽  
pp. 511-513
Author(s):  
A. Al-Saadi ◽  
D. Sprague ◽  
M. Sugden ◽  
A. Goode ◽  
S. Orr
Keyword(s):  
Body Weight ◽  
Glucose Production ◽  
Fold Increase ◽  
Isolated Hepatocytes ◽  
Major Product ◽  
Control Value ◽  
Metabolic Characteristics ◽  
Reverse Triiodothyronine ◽  
14Co2 Release

1. Reverse tri-iodothyronine (3,3′,5′-tri-iodothyronine, rT3), a major product of the peripheral monodeiodination of thyroxine, was administered subcutaneously to fed rats at a dose of 100 μg/100 g body weight for 2 consecutive days. 2. This dose induced a 17-fold increase in plasma rT3 (from 0.05±sem 0.01 to 0.85±0.11 ng/ml, P > 0.001) whilst the plasma T3 concentration was decreased to half of the control value (0.40 ± 0.03 to 0.20 ± 0.02 ng/ml, P > 0.01). 3. As a result of these changes the T3/rT3 ratio was therefore decreased from 8.0 ±1.6 to 0.23 ± 0.03 (P > 0.001). 4. Hepatocytes prepared from control or rT3treated rats were incubated with [l-14C]oleate and the rates of 14CO2 release and glucose production were estimated. Despite the changes in ratio of T3 to rT3 observed in vivo, rates of 14CO2 release and glucose production rate from hepatocytes subsequently isolated were unchanged.

Regulation of glucose production in rainbow trout: role of epinephrine in vivo and in isolated hepatocytes

2000 ◽  
Vol 278 (4) ◽  
pp. R956-R963 ◽  
Author(s):  
Jean-Michel Weber ◽  
Deena S. Shanghavi
Keyword(s):  
Rainbow Trout ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Isolated Hepatocytes ◽  
Relative Increase ◽  
Dependent Manner ◽  
Rainbow Trout Oncorhynchus Mykiss

The rate of hepatic glucose production (Ra glucose) of rainbow trout ( Oncorhynchus mykiss) was measured in vivo by continuous infusion of [6-3H]glucose and in vitro on isolated hepatocytes to examine the role of epinephrine (Epi) in its regulation. By elevating Epi concentration and/or blocking β-adrenoreceptors with propranolol (Prop), our goals were to investigate the mechanism for Epi-induced hyperglycemia to determine the possible role played by basal Epi concentration in maintaining resting Ra glucose and to assess indirect effects of Epi in the intact animal. In vivo infusion of Epi caused hyperglycemia (3.75 ± 0.16 to 8.75 ± 0.54 mM) and a twofold increase in Ra glucose (6.57 ± 0.79 to 13.30 ± 1.78 μmol ⋅ kg− 1 ⋅ min− 1, n = 7), whereas Prop infusion decreased Ra from 7.65 ± 0.92 to 4.10 ± 0.56 μmol ⋅ kg− 1 ⋅ min− 1( n = 10). Isolated hepatocytes increased glucose production when treated with Epi, and this response was abolished in the presence of Prop. We conclude that Epi-induced trout hyperglycemia is entirely caused by an increase in Ra glucose, because the decrease in the rate of glucose disappearance normally seen in mammals does not occur in trout. Basal circulating levels of Epi are involved in maintaining resting Ra glucose. Epi stimulates in vitro glucose production in a dose-dependent manner, and its effects are mainly mediated by β-adrenoreceptors. Isolated trout hepatocytes produce glucose at one-half the basal rate measured in vivo, even when diet, temperature, and body size are standardized, and basal circulating Epi is responsible for part of this discrepancy. The relative increase in Ra glucose after Epi stimulation is similar in vivo and in vitro, suggesting that indirect in vivo effects of Epi, such as changes in hepatic blood flow or in other circulating hormones, do not play an important role in the regulation of glucose production in trout.

Influence of C-ANF receptor and neutral endopeptidase on pharmacokinetics of ANF in rats

1991 ◽  
Vol 260 (1) ◽  
pp. R208-R216 ◽  
Author(s):  
P. J. Chiu ◽  
G. Tetzloff ◽  
M. T. Romano ◽  
C. J. Foster ◽  
E. J. Sybertz
Keyword(s):  
High Performance ◽  
Fold Increase ◽  
Neutral Endopeptidase ◽  
Volume Of Distribution ◽  
Fourfold Increase ◽  
Control Value ◽  
Enzymatic Pathways ◽  
Hydrolysis Of

The role of C-atrial natriuretic factor (ANF) receptors and neutral endopeptidase (NEP) in the pharmacokinetics and hydrolysis of 125I-labeled ANF was evaluated in rats by using C-ANF and SCH 39370 to block the nonenzymatic and enzymatic pathways, respectively. After a bolus injection of 125I-ANF, the resulting area under the plasma concentration curve (AUC) with C-ANF treatment was seven times the control value with regard to trichloroacetic acid-precipitable (TCA-ppt) radioactivity (intact ANF). SCH 39370 tended to increase AUC, but the changes were not significant. Nevertheless, SCH 39370 suppressed the appearance of TCA-soluble radioactivity (hydrolytic products), indicating that in vivo inhibition of ANF degradation had occurred. SCH 39370 plus C-ANF produced a 15-fold increase in AUC for TCA-ppt radioactivity and a reduction in plasma TCA-soluble radioactivity. High-performance liquid chromatography (HPLC) analysis confirmed that combination treatment increased intact ANF and reduced hydrolytic products in the plasma. SCH 39370 reduced clearance (C) without altering volume of distribution in steady state (Vss) and half-life (t1/2). C-ANF decreased both C and Vss leading to a fourfold increase in t1/2, which was further prolonged by SCH 39370 (7.5 times control). Bilateral nephrectomy caused a proportionally similar decrease in Vss and C without changing t1/2, suggesting significant extrarenal metabolism of ANF. SCH 39370 systemically inhibits ANF hydrolysis; the resulting increase in ANF, however, is masked by the great capacity of ANF clearance receptors but can be revealed with excess C-ANF, suggesting that the plasma ANF concentrations are determined by the interplay of the C-ANF receptor and NEP systems.

RES hyperphagocytosis by rats with streptozotocin-induced diabetes mellitus

1981 ◽  
Vol 240 (3) ◽  
pp. G225-G231
Author(s):  
R. P. Cornell
Keyword(s):  
Body Weight ◽  
Insulin Dose ◽  
Reticuloendothelial System ◽  
Diabetic Rats ◽  
Phagocytic Index ◽  
Control Value ◽  
Colloidal Carbon ◽  
Significant Difference

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.

scholarly journals Effect of diethylstilboestrol on phosphatidylcholine biosynthesis and choline metabolism in the liver of roosters

1981 ◽  
Vol 200 (2) ◽  
pp. 321-326 ◽  
Author(s):  
C Vigo ◽  
D E Vance
Keyword(s):  
Portal Vein ◽  
Fold Increase ◽  
Hormone Treatment ◽  
Phospholipid Metabolism ◽  
Choline Kinase ◽  
Control Value ◽  
Ctp:Phosphocholine Cytidylyltransferase ◽  
Choline Metabolism ◽  
Phosphatidylcholine Biosynthesis

It has been known for 40 years that oestrogens stimulate phospholipid metabolism in roosters. We have investigated in vivo the mechanism for this effect. Young roosters were injected daily with 1 mg of diethylstilboestrol for 1--3 days. At 4 h after the last injection, 30 microCi of [Me-3H]choline was injected into the portal vein. At periods up to 3 min the livers were freeze-clamped and choline and its metabolites were extracted and resolved by t.l.c. Hormone treatment in the first 2 days resulted in a 2-fold increase in phosphorylation of [Me-3H]choline and a decrease in the oxidation of [Me-3H]choline to [3H]betaine. The concentrations of phosphocholine in liver were increased 2-fold during the first 2 days concomitant with a 2-fold increase in the rate of phosphatidylcholine biosynthesis. After 3 days of hormone treatment, many of the above effects were reversed and the rate of phosphatidylcholine biosynthesis decreased to approx. 60% of the control value. The results suggest that the initial hormone treatments activate choline kinase within 4 h and, thereby, divert choline form oxidation to betaine. The resulting increased phosphocholine concentrations cause an increase in the activity of CTP:phosphocholine cytidylyltransferase, which results in a doubling of the rate of phosphatidylcholine biosynthesis. After 3 days of hormone treatment, the biosynthesis of phosphatidylcholine is decreased, most likely by an effect on the cytidylyltransferase reaction.

scholarly journals SUN-LB104 Metabolic Inflexibility: Is It a Feature of Obesity or a Characteristic of Metabolically Unhealthy Youth?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nour Y Gebara ◽  
Joon Young Kim ◽  
Fida Bacha ◽  
SoJung Lee ◽  
Silva A Arslanian
Keyword(s):  
Body Fat ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Normal Weight ◽  
Whole Body ◽  
Fasting Insulin ◽  
Metabolic Characteristics ◽  
Metabolically Healthy Obese ◽  
Metabolic Inflexibility

Abstract Obese individuals have metabolic inflexibility evidenced by diminished fasting fat oxidation and blunted increase in respiratory quotient (RQ) from fasting to insulin-stimulated state. Metabolically unhealthy obese (MUHO) adolescents, unlike their metabolically healthy obese (MHO) peers, have unfavorable metabolic characteristics despite having comparable adiposity. We investigated if metabolic inflexibility is a characteristic of obesity per se or is unique to MUHO compared with MHO youth. Obese youth (n=188; age 14.1 ± 0.1 yrs [SE]; BMI 33.6 ± 0.4 kg/m2) were divided into 137 MUHO (age 14.1 ± 0.2 yrs; BMI 35.4 ± 0.5 kg/m2) and 51 MHO (age 13.9 ± 0.3 yrs; BMI 29.0 ± 0.7 kg/m2) based on cut points for in vivo insulin sensitivity (IS) [MHO within 1.5 SD and MUHO <1.5 SDs of 72 normal-weight (NW) adolescents’ IS values]. RQ (by indirect calorimetry) at fasting and during a hyperinsulinemic (80mu/m2/min)-euglycemic clamp was measured, and ∆RQ calculated. Body composition (by DEXA), visceral adipose tissue (VAT) (by CT and MRI), hepatic IS (HIS) (calculated from fasting hepatic glucose production by [6,6-2H2]glucose and fasting insulin), adipose IS (ATIS) (calculated from whole body lipolysis by [2H5]glycerol and fasting insulin), and peripheral IS were assessed. MUHO vs. MHO youth had blunted ∆RQ (0.088 ± 0.004 vs. 0.107 ± 0.007, p=0.035), but MHO was not different from NW (0.098 ± 0.004, p=0.893). Further, MUHO vs. MHO youth had lower HIS (15.3 ± 0.7 vs. 24.3 ± 1.6 (mg/kg/min·uU/mL)-1, p<0.0001) and lower ATIS (9.8 ± 0.5 vs. 22.3 ± 3.1 (umol/kg/min·uU/mL)-1, p<0.0001), but HIS and ATIS were not different between MHO and NW youth (24.3 ± 1.6 vs. 20.8 ± 1.2 (mg/kg/min·uU/mL)-1, and 22.3 ± 3.1 vs. 22.0 ± 1.4 (umol/kg/min·uU/mL)-1, p=ns for both). ∆RQ correlated with HIS (r=0.535), ATIS (r=0.288) and VAT (r=-0.309) (p<0.0001 for all), but not with BMI, BMI Z-scores or % body fat. The differences between MUHO and MHO youth in ∆RQ, HIS and ATIS remained significant after adjusting for % body fat, race, pubertal status and VAT. The present study reveals that metabolic inflexibility is not a feature of obesity, rather it is a characteristic of MUHO youth who have significantly lower ∆RQ compared with MHO youth, with no difference between MHO and NW youth. Moreover, MUHO compared with MHO youth have worse metabolic profile, represented in lower HIS and ATIS.

scholarly journals Thyroid hormones modulate the endocrine and autocrine/paracrine actions of leptin on thyrotropin secretion

2004 ◽  
Vol 183 (1) ◽  
pp. 243-247 ◽  
Author(s):  
M A L Costa da Veiga ◽  
K de Jesus Oliveira ◽  
F H Curty ◽  
C C Pazos de Moura
Keyword(s):  
Body Weight ◽  
Thyroid Hormones ◽  
Inhibitory Action ◽  
Fold Increase ◽  
Short Term ◽  
Tsh Secretion ◽  
Paracrine Actions ◽  
Serum Tsh

We investigated the influence of hypo- and hyperthyroidism on the ability of leptin to modulate TSH secretion. Two hours after receiving leptin (8 μg leptin/100 g BW; s.c.), hyperthyroid rats (10 μg thyroxine (T4)/100 g body weight (BW) for 5 days) showed a 1.7-fold increase in serum TSH (P<0.05); in hypothyroid rats, leptin had no effect. Hemi-pituitaries of hyperthyroid rats incubated with 10−9 and 10−7M leptin showed reductions in TSH release of 40 and 50% respectively (P<0.05); incubation with 1:2000 and 1:500 dilutions of antiserum against leptin resulted in 3- and 4-fold higher TSH release (P<0.05 and P<0.001 respectively). However, in hypothyroid pituitaries leptin or the antiserum had no effect. The results suggest that the in vivo and in vitro responsiveness of TSH to leptin is abolished in hypothyroidism and is preserved in short-term hyperthyroidism, in comparison to previous reports in euthyroidism. In addition, the inhibitory action of pituitary leptin is enhanced in hyperthyroid glands, which may suggest a role for locally produced leptin in the suppression of TSH release associated with hyperthyroidism.

scholarly journals Uptake and binding of cadmium and mercury to metallothionein in rat hepatocyte primary cultures

1982 ◽  
Vol 208 (2) ◽  
pp. 465-472 ◽  
Author(s):  
Ronald J. Gerson ◽  
Zahir A. Shaikh
Keyword(s):  
Time Course ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Isolated Hepatocytes ◽  
Fresh Medium ◽  
Control Value ◽  
Dispositional Differences ◽  
Insight Into ◽  
Hepatocyte Monolayer

The administration of inorganic Cd and Hg in vivo has been shown to result in markedly different metal concentrations in rat liver. Primary cultures of rat hepatocytes were utilized to gain insight into the dispositional differences between these chemically similar metals. Hepatocyte monolayer cultures were exposed to several concentrations of Cd or Hg (3, 10 and 30μm) in serum-containing medium for 30min. The cells were then washed and incubated in fresh medium for the remainder of the experiment. Hepatocytes exposed to Cd accumulated significantly more metal than hepatocytes exposed to equimolar concentrations of Hg. In cells exposed to 3μm-Cd there was an initial loss of Cd from the hepatocytes when placed in fresh medium, followed by a gradual re-uptake of metal, concomitant with increased binding to metallothionein. In hepatocytes exposed to 3 and 10μm-Cd, 87 and 77% of the intracellular Cd was bound to metallothionein within 24h. Loss of Hg from hepatocytes pulsed with 30μm-Hg was also observed upon the addition of fresh medium and continued for the duration of the experiment. No time-dependent increase in Hg binding to metallothionein was observed. A maximum of about 10% of the intracellular Hg was found associated with metallothionein in hepatocytes exposed to 30μm-Hg. Studies utilizing [35S]cysteine incorporation indicated significant increases in the amount of metallothionein synthesized in hepatocytes exposed to 3 and 10μm-Cd (300% of control value) and 30μm-Hg (150% of control value) 24h after metal pulsing. Time-course studies revealed a 6–12h lag in metallothionein synthesis, followed by a significant elevation in [35S]cysteine incorporation into metallothionein between 12 and 24h. These studies suggest that (a) isolated hepatocytes differentiate between Cd and Hg and preferentially accumulate the former, and (b) Cd strongly stimulates the induction of, and preferentially binds to, metallothionein, whereas Hg induces weakly, and does not preferentially bind to, metallothionein.

Use of growth-hormone-releasing peptide-6 (GHRP-6) for the prevention of multiple organ failure

2006 ◽  
Vol 110 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Danay Cibrián ◽  
Hussam Ajamieh ◽  
Jorge Berlanga ◽  
Olga S. León ◽  
Jose S. Alba ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Cell Migration ◽  
Multiple Organ Failure ◽  
Fold Increase ◽  
Multiple Organ ◽  
Ht29 Cells ◽  
Ischaemia Reperfusion

Novel therapies for the treatment of MOF (multiple organ failure) are required. In the present study, we examined the effect of synthetic GHRP-6 (growth hormone-releasing peptide-6) on cell migration and proliferation using rat intestinal epithelial (IEC-6) and human colonic cancer (HT29) cells as in vitro models of injury. In addition, we examined its efficacy when given alone and in combination with the potent protective factor EGF (epidermal growth factor) in an in vivo model of MOF (using two hepatic vessel ischaemia/reperfusion protocols; 45 min of ischaemia and 45 min of reperfusion or 90 min of ischaemia and 120 min of reperfusion). In vitro studies showed that GHRP-6 directly influenced gut epithelial function as its addition caused a 3-fold increase in the rate of cell migration of IEC-6 and HT29 cells (P<0.01), but did not increase proliferation ([3H]thymidine incorporation). In vivo studies showed that, compared with baseline values, ischaemia/reperfusion caused marked hepatic and intestinal damage (histological scoring), neutrophilic infiltration (myeloperoxidase assay; 5-fold increase) and lipid peroxidation (malondialdehyde assay; 4-fold increase). Pre-treatment with GHRP-6 (120 μg/kg of body weight, intraperitoneally) alone truncated these effects by 50–85% (all P<0.05) and an additional benefit was seen when GHRP-6 was used in combination with EGF (1 mg/kg of body weight, intraperitoneally). Lung and renal injuries were also reduced by these pre-treatments. In conclusion, administration of GHRP-6, given alone or in combination with EGF to enhance its effects, may provide a novel simple approach for the prevention and treatment of MOF and other injuries of the gastrointestinal tract. In view of these findings, further studies appear justified.

scholarly journals Sodium Meta-Arsenite Ameliorates Hyperglycemia in Obese Diabeticdb/dbMice by Inhibition of Hepatic Gluconeogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Young-Sun Lee ◽  
Eun-Kyu Lee ◽  
Hyun-Hee Oh ◽  
Cheol Soo Choi ◽  
Sujong Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Diabetic Mouse ◽  
Hepatic Gluconeogenesis ◽  
Glucose Levels ◽  
Blood Glucose Levels

Sodium meta-arsenite (SA) is implicated in the regulation of hepatic gluconeogenesis-related genesin vitro; however, the effectsin vivohave not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabeticdb/dbmice were orally intubated with SA (10 mg kg−1body weight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabeticdb/dbmice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver of SA-treated diabeticdb/dbmice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α) mRNA. Small heterodimer partner (SHP) mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated diabeticdb/dbmice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia indb/dbmice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1.

Comparison of Specific Antibody, D-Phe-Pro-Arg-CH2Cl and Aprotinin for Prevention of In Vitro Effects of Recombinant Tissue-Type Plasminogen Activator on Haemostasis Parameters

1987 ◽  
Vol 58 (03) ◽  
pp. 921-926 ◽  
Author(s):  
E Seifried ◽  
P Tanswell
Keyword(s):  
Specific Antibody ◽  
Plasma Concentrations ◽  
Fibrinolytic Therapy ◽  
Tissue Type ◽  
Control Value ◽  
Type Plasminogen Activator ◽  
In Vitro Effects ◽  
Fibrinolytic Parameters

SummaryIn vitro, concentration-dependent effects of rt-PA on a range of coagulation and fibrinolytic assays in thawed plasma samples were investigated. In absence of a fibrinolytic inhibitor, 2 μg rt-PA/ml blood (3.4 μg/ml plasma) caused prolongation of clotting time assays and decreases of plasminogen (to 44% of the control value), fibrinogen (to 27%), α2-antiplasmin (to 5%), FV (to 67%), FVIII (to 41%) and FXIII (to 16%).Of three inhibitors tested, a specific polyclonal anti-rt-PA antibody prevented interferences in all fibrinolytic and most clotting assays. D-Phe-Pro-Arg-CH2Cl (PPACK) enabled correct assays of fibrinogen and fibrinolytic parameters but interfered with coagulometric assays dependent on endogenous thrombin generation. Aprotinin was suitable only for a restricted range of both assay types.Most in vitro effects were observed only with rt-PA plasma concentrations in excess of therapeutic values. Nevertheless it is concluded that for clinical application, collection of blood samples on either specific antibody or PPACK is essential for a correct assessment of in vivo effects of rt-PA on the haemostatic system in patients undergoing fibrinolytic therapy.

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