Evaluation of the liver functional changes in modeling the hemodynamic effects of microgravity in bed rest studies

Ultrasonic examinations of eight male volunteers during bed rest in the antiorthostatic position (ANOP) at–15° showed plethora in the venous system of the abdominal cavity and slow blood flow through the liver with no effect on biochemical parameters. The ¹³C-methcetine breath test (¹³C-MBT) with 100 mg of ¹³C-methoxymethacetine showed diminution of the metabolic capacity and decline in the rate of detoxification activity of the liver due to functional changes related to hemodynamic alterations in ANOP. ¹³C-MBT can be used as a noninvasive method for diagnosing functional changes in the liver induced by hemodynamic reorganization in microgravity and other states triggering similar hemodynamic mechanisms.     

13C-methacetin breath test parameter S for liver diseases diagnosis

The mechanism of ¹³C-methacetin breath test is set forth clearly with the analysis of pharmacokinetics mode, and the measuring method of ¹³C-methacetin breath test and its clinical applications in the diagnosis of liver diseases are reported in detail. On the basis of comprehensive analysis of the clinical test data, the advanced diagnostic parameter S is of important significance for the application and development of breath test.     

Assessment of Hepatic Detoxification Activity: Proposal of an Improved Variant of the 13C-Methacetin Breath Test

Breath tests based on the administration of a ¹³C-labeled drug and subsequent monitoring of ¹³CO₂ in the breath (quantified as DOB – delta over baseline) liberated from the drug during hepatic CPY-dependent detoxification are important tools in liver function diagnostics. The capability of such breath tests to reliably indicate hepatic CYP performance is limited by the fact that ¹³CO₂ is not exclusively exhaled but also exchanged with other compartments of the body. In order to assess this bias caused by variations of individual systemic CO₂ kinetics we administered intravenously the test drug ¹³C-methacetin to 25 clinically liver-healthy individuals and monitored progress curves of DOB and the plasma concentration of ¹³C-methacetin. Applying compartment modelling we estimated for each individual a set of kinetic parameters characterizing the time-dependent exchange of the drug and of CO₂ with the liver and non-hepatic body compartments. This analysis revealed that individual variations in the kinetics of CO₂ may account for up to 30% deviation of DOB curve parameters from their mean at otherwise identical ¹³C-methacetin metabolization rates. In order to correct for this bias we introduced a novel detoxification score which ideally should be assessed from the DOB curve of a 2-step test (“2DOB”) which is initialized with the injection of a standard dose of ¹³C-labeled bicarbonate (in order to provide information on the actual CO₂ status of the individual) followed by injection of the ¹³C-labeled test drug (the common procedure). Computer simulations suggest that the predictive power of the proposed 2DOB breath test to reliably quantity the CYP-specific hepatic detoxification activity should be significantly higher compared to the conventional breath test.     

A competing salt-bridge suppresses helix formation by the isolated C-peptide carboxylate of ribonuclease A

The C-peptide of ribonuclease A (residues 1 to 13) is obtained by cyanogen bromide cleavage at Met13, which converts methionine to a mixture of homoserine lactone (giving C-peptide lactone) and homoserine carboxylate (giving C-peptide carboxylate). The helix-forming properties of C-peptide lactone have been reported. The helix is formed intramolecularly in aqueous solution, is stabilized at low temperatures (0 to 20 °C) and also by a pH-dependent interaction between sidechains. The C-peptide lactone helix is about 1000-fold more stable than expected from “host-guest” data for helix formation in synthetic polypeptides.Here we report the failure of C-peptide carboxylate to form an α-helix in comparable conditions. Formation of a salt-bridge between the α-COO^? group and the imidazolium ring of His12⁺ appears to be responsible for the suppression of helix formation. The presence of the Hse13-COO^? … His12⁺ salt-bridge in C-peptide carboxylate is shown by ¹H nuclear magnetic resonance titration of the amide proton resonances of His12 and Hse13, and is expected from model peptide studies. The most probable reason why C-peptide carboxylate does not form an α-helix is that the Hse13-COO^? … His12⁺ salt-bridge competes successfully with a helix stabilizing salt-bridge (Glu9^? … His12⁺).S-peptide (residues 1 to 20 of ribonuclease A) does form an α-helix with properties similar to those of the C-peptide (lactone) helix, which shows that the lactone ring of C-peptide lactone is not needed for helix formation.These results support the hypothesis that a Glu9^? … His12⁺ salt-bridge stabilizes the C-peptide (lactone) helix, and they show that specific interactions between side-chains can be important in preventing as well as in promoting α-helix formation.     

Amide 1H n.m.r. study of the folding of ribonuclease C-peptide

The folding of ribonuclease A 1–13 (C-peptide) in H₂O near 0°C has been monitored by means of the amide and side chain NH proton resonances. The C-peptide carboxylate at low temperature forms, in a significant amount, a folded structure similar to the one that the 1–19 S-peptide adopts in the same conditions (3–13 α-helix). A quantitative comparison between helix stabilities of the lactone and carboxylate forms of C-peptide and S-peptide is reported. It is concluded that the proposed His 12⁺ … Hse 13 (COO^? salt bridge, which competes with the one-turn stabilizing salt bridge His 12⁺ … Glu 9^? in the C-peptide carboxylate, does not suppress helix formation as previously suggested but it merely reduces its stability. The behaviour of the N⁵-H resonance of the Arg 10⁺ side chain provides evidence for its implication in a further stabilizing interaction, most probably with Glu 2^?.     

Inactivation of Calcitonin by Specific Organs

THE greater biological potency of salmon calcitonin (SCT) as compared with mammalian calcitonins may be due to the relative resistance of SCT to inactivation in vivo^1,2. SCT infused into dogs disappears from the circulation more slowly than does porcine calcitonin (PCT) or human calcitonin (HCT)^1–3. For example, the metabolic clearance rate (MCR) of PCT in the dog is approximately 10 times greater than that of SCT^1,2. Neither renal excretion^3,4 nor inactivation by plasma^1,2 is sufficient to account for the rapid clearance of the calcitonins that we have observed in vivo and thus it seemed likely that inactivation of the hormones must occur during passage through one or more organs. Here we present data that suggest the kidney, the liver and muscle and/or bone as the sites of inactivation of the calcitonins in the dog. SCT is relatively resistant to inactivation in the latter two sites.     

Characteristics of the amylase of Arthrobacter psychrolactophilus

Properties of the extracellular amylase produced by the psychrotrophic bacterium, Arthrobacter psychrolactophilus, were determined for crude preparations and purified enzyme. The hydrolysis of soluble starch by concentrated crude preparations was found to be a nonlinear function of time at 30 and 40 °C. Concentrates of supernatant fractions incubated without substrate exhibited poor stability at 30, 40, or 50 °C, with 87% inactivation after 21 h at 30 °C, 45% inactivation after 40 min at 40 °C and 90% inactivation after 10 min at 50 °C. Proteases known to be present in crude preparations had a temperature optimum of 50 °C, but accounted for a small fraction of thermal instability. Inactivation at 30, 40, or 50 °C was not slowed by adding 20 mg/ml bovine serum albumin or protease inhibitor cocktail to the preparations or the assays to protect against proteases. Purified amylase preparations were almost as thermally sensitive in the absence of substrate as crude preparations. The temperature optimum of the amylase in short incubations with Sigma Infinity Amylase Reagent was about 50 °C, and the amylase required Ca⁺² for activity. The optimal pH for activity was 5.0–9.0 on soluble starch (30 °C), and the amylase exhibited a K _m with 4-nitrophenyl-α-D-maltoheptaoside-4,6-O-ethylidene of 120 μM at 22 °C. The amylase in crude concentrates initially hydrolyzed raw starch at 30 °C at about the same rate as an equal number of units of barley α-amylase, but lost most of its activity after only a few hours.     

~(13)C-methacetin breath test parameter S for liver diseases diagnosis

The mechanism of 13C-methacetin breath test is set forth clearly with the analysis of pharmacokinetics mode, and the measuring method of 13C-methacetin breath test and its clinical applications in the diagnosis of liver diseases are reported in detail. On the basis of comprehensive analysis of the clinical test data, the advanced diagnostic parameter S is of important significance for the application and development of breath test.     

Dose-dependent inhibitory and non-inhibitory action of somatostatin on insulin release in rats

The dose-dependent effect of intravenously infused synthetic somatostatin-14 on basal and postprandial insulin and gastrin release was assessed in anesthetized rats.Infusion of 1 ng · kg^?1 · min^?1 elicited a significant reduction of basal and postprandial insulin levels compared to the saline control group. At 15 ng · kg^?1 · min^?1 basal insulin was not affected but postprandial insulin levels were still significantly reduced. At 30 ng · kg^?1 · min^?1 neither basal nor stimulated insulin levels were affected. At the highest concentration of 120 ng · kg^?1 · min^?1 basal and postprandial insulin levels were suppressed similar to the lowest infusion rate of 1 ng · kg^?1 · min^?1. Basal gastrin levels were significantly reduced only at the highest rate of 120 ng · kg^?1 · min^?1. A significant reduction of postprandial gastrin levels was observed at 15 ng · kg^?1 · min^?1 and all higher infusion rates employed. Measurements of plasma somatostatin-like immunoreactivity (SLI) demonstrated that plasma SLI levels during the lowest infusion rate of 1 ng · kg^?1 · min^?1 were not different from the controls. No significant rise of plasma SLI levels was observed in response to the test meal. The higher infusion rates elicited a dose-dependent increase in plasma SLI levels. These data demonstrate that in rats somatostatin exerts a biological effect on insulin release at very low doses while certain greater infusion rates have no suppressive effect. Gastrin secretion is inhibited in a more linear pattern.     

Inactivation by Na+,K+-ATPase of cytosol glucocorticoid receptors from rat brain and liver

Summary We have examined the effect of Na⁺,K⁺-ATPase on ³H-triamcinolone acetonide binding capacity of cytosol glucocorticoid receptors from rat brain and liver. Preincubation of the brain or liver cytosol with Na⁺,K⁺-ATPase (10 units/ml) at 30 °C resulted in a rapid loss of specific ³H-triamcinolone acetonide binding, with a half-life of approximately 7 min. The ATPase effect could be prevented by the addition of 10^–5 M ouabain, or substantially reduced by the omission of Na⁺,K⁺ or Mg⁺². The cytosol receptor bound with ³H-triamcinolone acetonide was totally resistant to the inactivation by the ATPase. Since there is some evidence that ATP may bind to glucocorticoid receptor, our findings indicate that an ATP-receptor complex may be essential for steroid binding. The effects of the ATPase in the inactivation of the receptor are very similar to those of alkaline phosphatase reported by others. This raises doubts about the proposal based on the phosphatase inactivation that the cytosol glucocorticoid receptor may be phosphorylated.     

Cortical metabolism in pyruvate dehydrogenase deficiency revealed by ex vivo multiplet C NMR of the adult mouse brain

The pyruvate dehydrogenase complex (PDC), required for complete glucose oxidation, is essential for brain development. Although PDC deficiency is associated with a severe clinical syndrome, little is known about its effects on either substrate oxidation or synthesis of key metabolites such as glutamate and glutamine. Computational simulations of brain metabolism indicated that a 25% reduction in flux through PDC and a corresponding increase in flux from an alternative source of acetyl-CoA would substantially alter the ¹³C NMR spectrum obtained from brain tissue. Therefore, we evaluated metabolism of [1,6-¹³C₂]glucose (oxidized by both neurons and glia) and [1,2-¹³C₂]acetate (an energy source that bypasses PDC) in the cerebral cortex of adult mice mildly and selectively deficient in brain PDC activity, a viable model that recapitulates the human disorder. Intravenous infusions were performed in conscious mice and extracts of brain tissue were studied by ¹³C NMR. We hypothesized that mice deficient in PDC must increase the proportion of energy derived from acetate metabolism in the brain. Unexpectedly, the distribution of ¹³C in glutamate and glutamine, a measure of the relative flux of acetate and glucose into the citric acid cycle, was not altered. The ¹³C labeling pattern in glutamate differed significantly from glutamine, indicating preferential oxidation of [1,2-¹³C]acetate relative to [1,6-¹³C]glucose by a readily discernible metabolic domain of the brain of both normal and mutant mice, presumably glia. These findings illustrate that metabolic compartmentation is preserved in the PDC-deficient cerebral cortex, probably reflecting intact neuron–glia metabolic interactions, and that a reduction in brain PDC activity sufficient to induce cerebral dysgenesis during development does not appreciably disrupt energy metabolism in the mature brain.     

Amylase release from rat parotid glands I. General characteristics

The involvement of calcium, ATP, and cyclic AMP-dependent protein kinase activity in the release of amylase from rat parotid glands was examined. Pretreatment of the glandular tissue in 11.25 mM Ca²⁺ medium potentiated the secretory responses to: dibutyryl cyclic AMP, elevation of the extracellular K⁺ concentration, reduction of the H⁺ concentration, La³⁺, and caffeine. Uncoupling of oxidative phosphorylation blocked release induced by dibutyryl cyclic AMP, K⁺, and reduction of H⁺, but had no effect on La³⁺, caffeine or tolbutamide-stimulated release. Inhibition of cyclic AMP-dependent protein kinase activity blocked only dibutyryl cyclic AMP-induced release and did not inhibit the responses to K⁺, reduction of H⁺ or caffeine.The loss of lactate dehydrogenase was used to access the integrity of the tissue during amylase release. No significant increase in the release of lactate dehydrogenase was observed during the secretory responses to: dibutyryl cyclic AMP, La³⁺, caffeine, or tolbutamide. Triton X-100 and ethanol increased the efflux of both amylase and lactate dehydrogenase.The differential involvement of Ca²⁺, ATP, and cyclic AMP-dependent protein kinase activity in amylase release induced by the various secretagogues suggests that three types of reactions are involved in the release of amylase.     

Metabolic response of <Emphasis Type="Italic">Geobacter sulfurreducens</Emphasis> towards electron donor/acceptor variation

Background  

Geobacter sulfurreducens is capable of coupling the complete oxidation of organic compounds to iron reduction. The metabolic response of G. sulfurreducens towards variations in electron donors (acetate, hydrogen) and acceptors (Fe(III), fumarate) was investigated via ¹³C-based metabolic flux analysis. We examined the ¹³C-labeling patterns of proteinogenic amino acids obtained from G. sulfurreducens cultured with ¹³C-acetate.     

Antimicrobial mechanism and the effect of atmospheric pressure N2 plasma jet on the regeneration capacity of Staphylococcus aureus biofilm

Abstract

This study systematically assessed the inactivation mechanism on Staphylococcus aureus biofilms by a N₂ atmospheric-pressure plasma jet and the effect on the biofilm regeneration capacity from the bacteria which survived, and their progenies. The total bacterial populations were 7.18?±?0.34 log10 CFU ml^?1 in biofilms and these were effectively inactivated (>5.5-log10 CFU ml^?1) within 30?min of exposure. Meanwhile, >80% of the S. aureus biofilm cells lost their metabolic capacity. In comparison, ～20% of the plasma-treated bacteria entered a viable but non-culturable state. Moreover, the percentage of membrane-intact bacteria declined to ～30%. Scanning electron microscope images demonstrated cell shrinkage and deformation post-treatment. The total amount of intracellular reactive oxygen species was observed to have significantly increased in membrane-intact bacterial cells with increasing plasma dose. Notably, the N₂ plasma treatment could effectively inhibit the biofilm regeneration ability of the bacteria which survived, leading to a long-term phenotypic response and dose-dependent inactivation effect on S. aureus biofilms, in addition to the direct rapid bactericidal effect.     

Suppression of α‐Amylase inactivation in the presence of ethanol: Application of a two‐step model

A number of years ago we reported a two‐step inactivation mechanism for α‐amylase (enzyme) on the basis of theoretical and experimental studies in aqueous solutions. In the first step the metal (Ca²⁺) ion dissociates reversibly from the enzyme followed by an irreversible thermal inactivation of the apoenzyme. In this study we report inactivation of the enzyme in the presence of ethanol–water solutions. We noticed that as the concentration of ethanol in the aqueous solution is increased, the thermal inactivation of the enzyme is suppressed with almost no inactivation (in 1 h, 30°C) when 50% alcohol is present in the solution. These results are explained by the two‐step inactivation model. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1271–1275, 2016     

The postprandial use of dietary amino acids as an energy substrate is delayed after the deamination process in rats adapted for 2 weeks to a high protein diet

The aim of this study was to determine the contribution of dietary amino acids (AA) to energy metabolism under high protein (HP) diets, using a double tracer method to follow simultaneously the metabolic fate of α-amino groups and carbon skeletons. Sixty-seven male Wistar rats were fed a normal (NP) or HP diet for 14 days. Fifteen of them were equipped with a permanent catheter. On day 15, after fasting overnight, they received a 4-g meal extrinsically labeled with a mixture of 20 U-[¹⁵N]-[¹³C] AA. Energy metabolism, dietary AA deamination and oxidation and their transfer to plasma glucose were measured kinetically for 4 h in the catheterized rats. The transfer of dietary AA to liver glycogen was determined at 4 h. The digestive kinetics of dietary AA, their transfer into liver AA and proteins and the liver glycogen content were measured in the 52 other rats that were killed sequentially hourly over a 4-h period. [¹⁵N] and [¹³C] kinetics in the splanchnic protein pools were perfectly similar. Deamination increased fivefold in HP rats compared to NP rats. In the latter, all deaminated AA were oxidized. In HP rats, the oxidation rate was slower than deamination, so that half of the deaminated AA was non-oxidized within 4 h. Non-oxidized carbon skeletons were poorly sequestrated in glycogen, although there was a significant postprandial production of hepatic glycogen. Our results strongly suggest that excess dietary AA-derived carbon skeletons above the ATP production capacity, are temporarily retained in intermediate metabolic pools until the oxidative capacities of the liver are no longer overwhelmed by an excess of substrates.     

Effect of omeprazole on secretion,synthesis and the gene expression of pepsinogen in the guinea pig stomach mucosa

The effects of omeprazole, a proton pump inhibitor, on gene expression, protein synthesis, intracellular storage and secretion of pepsinogen in guinea pig stomach were investigated. After treatment with omeprazole for five days, acid and pepsinogen secretion into the gastric lumen was significantly reduced. Concomitant with this, there was an increase in intracellular pepsinogen as demonstrated by increased pepsin activity in the gastric mucosa, more intense immunohistochemical staining by antibodies specific of pepsinogen and accumulation of secretory granules in the cells producing pepsinogen. In these cells, the amount for pepsinogen mRNA was reduced as revealed by Northern blotting and in situ hybridization. Ultrastructurally the endoplasmic reticulum of these cells was poorly developed, the findings being consistent with a reduction in protein synthesis. It appears that omeprazole inhibits the secretion of pepsinogen, increasing the intracellular store and leading to the reduction in gene expression probably by a feedback mechanism and consequent reduction in pepsinogen synthesis. Since these changes were most evident in the acid-secreting fundic gland mucosa, as compared with other mucosae secreting only pepsinogen, namely pyloric and duodenal mucosa, it appears probable that these changes are linked with omeprazole-induced reduction in the acid secretion.     

Serum C-peptide levels and risk of death among adults without diabetes mellitus

Background:

Connecting peptide (C-peptide) plays a role in early atherogenesis in patients with diabetes mellitus and may be a marker for cardiovascular morbidity and mortality in patients without diabetes. We investigated whether serum C-peptide levels are associated with all-cause, cardiovascular-related and coronary artery disease–related mortality in adults without diabetes.

Methods:

We used data from the Third Nutrition and Health Examination Survey (NHANES III) and the NHANES III Linked Mortality File in the United States. We analyzed mortality data for 5902 participants aged 40 years and older with no history of diabetes and who had available serum C-peptide levels from the baseline examination. We grouped the participants by C-peptide quartile, and we performed Cox proportional hazards regression analysis. The primary outcome was all-cause, cardiovascular-related and coronary artery disease–related mortality.

Results:

The mean serum C-peptide level in the study sample was 0.78 (± standard deviation 0.47) nmol/L. The adjusted hazards ratio comparing the highest quartile with the lowest quartile was 1.80 (95% confidence interval [CI] 1.33–2.43) for all-cause mortality, 3.20 (95% CI 2.07–4.93) for cardiovascular-related mortality, and 2.73 (95% CI 1.55–4.82) for coronary artery disease–related mortality. Higher C-peptide levels were associated with increased mortality among strata of glycated hemoglobin and fasting serum glucose.

Interpretation:

We found an association between serum C-peptide levels and all-cause and cause-specific mortality among adults without diabetes at baseline. Our finding suggests that elevated C-peptide levels may be a predictor of death.Connecting peptide (C-peptide), a cleavage product of proinsulin, is secreted by pancreatic β cells in equimolar amounts along with insulin.¹ Although a considerable amount of insulin is extracted by the liver, C-peptide is subjected to negligible first-pass metabolism by the liver, thereby serving as a surrogate marker for endogenous insulin secretion.² C-peptide has been considered an inert by-product of insulin synthesis and has also been of great value in the understanding of the pathophysiology of type 1 and type 2 diabetes mellitus.^2,3 However, C-peptide has recently been re-evaluated as a bioactive peptide in its own right. The administration of C-peptide to patients and animals with type 1 diabetes has been reported to have a beneficial effect on diabetes-induced abnormalities of the peripheral nerves and renal and microvascular function.^4,5 C-peptide deposition occurs in the atherosclerotic lesions of patients with diabetes.⁶ Recent studies have suggested that C-peptide may be a valuable predictor of cardiovascular events and mortality (all-cause and cardiovascular-related mortality).^6–12In this study, we investigated the association between serum C-peptide level and all-cause, cardiovascular-related and coronary artery disease–related mortality among patients without diabetes. We also estimated mortality as C-peptide increased across glycated hemoglobin and fasting blood glucose quartiles.     

Metabolic depression and sodium-potassium ATPase in the aestivating frog, Neobatrachus kunapalari

In aestivation the metabolic rate of the Australian desert frog Neobatrachus kunapalari was 50–67% lower than in the non-aestivating state. The rate of O₂ consumption of isolated muscle, skin and brain was measured in both metabolic states. The average rate of O₂ consumption of muscle was 30% lower and brain 50% lower in aestivating frogs, while the rate of O₂ consumption of skin was the same. The reduction in muscle could account for a large proportion of whole animal metabolic depression. To look for evidence of a reduction in energy demand in the tissues we measured the ouabain-sensitive fraction of tissue rate of O₂ consumption, which is considered to be the proportion of metabolism used for transmembrane Na⁺/K⁺ pumping. Ouabain inhibited the in vitro rate of O₂ consumption of skin by a average of 20% and of brain by an average of 30%. However, in muscle, ouabain stimulated in vitro O₂ consumption. Despite the 50% reduction in the in vitro rate of O₂ consumption of brain during aestivation, neither the ouabain-sensitive nor ouabain-insensitive fractions were found be statistically different, possibly because of the large individual variation in the degree of ouabain inhibition. A reduction in the level of ion pumping during aestivation was therefore not demonstrated in any tissue. Measurement of the level of the enzyme Na⁺K⁺-ATPase in skeletal muscle, ventricle, kidney and brain showed that there was no change in the amount of this enzyme in the aestivating frogs. Measurement of the levels of adenylates in muscle and liver showed that the adenylate energy charge was maintained in aestivation, but that there was a reduction in ATP in liver and a reduction in the level of total adenylates in both tissues, which could be an adaptation of the tissues to a lower energy turnover. Accepted: 22 July 1996     

Increased Oxidative Metabolism and Neurotransmitter Cycling in the Brain of Mice Lacking the Thyroid Hormone Transporter Slc16a2 (Mct8)

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T₄ and T₃) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T₄ and T₃. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-¹³C) glucose and brain extracts prepared and analyzed by ¹³C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T₃ by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.