Biomedical subjects

Y Mimura

Publications and source records attributed to Y Mimura.

At least 91 records · Page 5Linked to original sources

PubMed1995

[Phosphaturic effect of PTH during hypoxia and hypocapnia in rats].

This study examined the effect of acute hypoxia or hypocapnia on renal phosphate excretion in thyroparathyroidectomized rats. Hypoxia is usually accompanied by a secondary hypocapnia due to hypoxic hyperventilation. Respiratory alkalosis has been described as blunting the phosphaturic effect of parathyroid hormone (PTH). In the present study, to know the effect of hypoxia on renal phosphate excretion in the absence of hypocapnia, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. The rats were divided into three groups depending on the arterial PO2 and PCO2 levels: 1) hypoxic normocapnic group; 2) normoxic normocapnic group; 3) normoxic hypocapnic group. Hypoxia was achieved by ventilating with 10% oxygen, and hypocapnia by hyperventilating with 25-30% oxygen. PTH infusion significantly increased fractional excretion of phosphate (FEPi) from 4.1 +/- 0.9 (mean +/- SE) to 37.7 +/- 2.6% in the hypoxic group (n = 7), from 1.4 +/- 0.3 to 27.4 +/- 2.5% in the normoxic group (n = 8), and from 1.5 +/- 0.4 to 19.5 +/- 1.2% in the hypocapnic group (n = 10). The change of FEPi (delta FEPi) after PTH infusion during hypoxia was significantly greater (33.6 +/- 2.1%) than that during normoxia (26.1 +/- 2.4%, p < 0.05). In contrast to this, hypocapnia blunted the phosphaturic response to PTH (18.0 +/- 1.1% delta FEPi, p < 0.05). Urinary adenosine 3', 5'-cyclic monophosphate (cAMP) increased similarly after PTH infusion in all three groups. To test whether the enhanced phosphaturic effect of PTH during hypoxia and the blunted phosphaturic effect of PTH during hypocapnia are due to steps beyond the production of cAMP, cAMP was administered to the three groups. Cyclic AMP infusion displayed greater phosphaturia in the hypoxic group (n = 6, 30.0 +/- 1.4%) and less phosphaturia in the hypocapnic group (n = 7, 11.3 +/- 1.8%) as compared the the normoxic group (n = 6, 24.1 +/- 1.0%). In conclusion, acute hypoxia enhances the phosphaturic effect of PTH, whereas acute hypocapnia attenuates the phosphaturic effect of PTH.

Animals↗

PubMed1995

[Acute hypocapnia attenuates phosphaturic effect of atrial natriuretic peptide in rats].

This study evaluated phosphate excretion in response to atrial natriuretic peptide during acute hypocapnia in the presence or absence of the renal nerves in rats. To achieve a hypocapnic state, rats were mechanically hyperventilated with room air. As mechanical ventilation per se has been reported to affect renal excretory functions depending on the ventilatory conditions, this study was designed to examine renal functions during acute hypocapnia as compared with those during normocapnia produced by normal and/or hyperventilation. Rats were divided into three experimental groups: 1) a normally ventilated normocapnic (control) group (n = 8), 2) a hyperventilated normocapnic group (n = 8), and 3) a hyperventilated hypocapnic group (n = 8). The innervated right kidney served as a control for the contralateral denervated kidney. Acute renal denervation produced a greater phosphaturia compared to the innervated kidney during the control period in the two normocanic groups but not in the hypocapnic group. Infusion of ANP 12 micrograms/kg/h produced a remarkable increase in phosphate excretion in either kidney in the normocapnic groups. The degree of the phosphaturia (delta FEPi%) during infusion of ANP was similar between the normally ventilated and hyperventilated normocapnic groups both in innervated (10.6 +/- 2.4% and 7.4 +/- 1.2%) and denervated (14.0 +/- 3.0% and 13.5 +/- 2.2%) kidneys. In contrast to both normocapnic groups, the hypocapnic group had a greater hypophosphaturia during the control and ANP infusion periods in either kidney. The increase in fractional excretion of phosphate was smaller both in innervated (0.34 +/- 0.34% delta FEPi) and denervated (0.72 +/- 0.69% delta FEPi) kidneys than that in the other two normocapnic groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

Microheterogeneity of mouse antidextran monoclonal antibodies.

Mouse antidextran monoclonal antibodies showed microheterogeneity which was analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Not only the heavy (H) chains but also the light (L) chains were heterogeneous in terms of isoelectric point (pI). The higher the pI, the more prominent the H chain spots. To demonstrate the cause of the microheterogeneity an IgG1 monoclonal antibody (mAb 35.8.2H) was examined especially for involvement of the sugar moiety in the microheterogeneity. The glycosylated region was determined in the Fc portion from serine 239 to methionine 309 by a glycan detection method using mild periodate oxidation, which confirms that the sugar chain is attached to the conserved glycosylation site of asparagine 297. However, charge heterogeneity of the H chain was not entirely attributed to the Fc because the papain digest of the antibody was separated into two Fc spots, a few Fd spots and two L chain spots by 2-D PAGE. This indicates that factors other than the sugar moiety are responsible for charge heterogeneity of IgG monoclonal antibody. On the other hand, the H chain isoforms of lower pI were shown to be more susceptible to V8 protease by peptide mapping. This result strongly suggests the occurrence of deamidation at glutamine or asparagine residues.

Amino Acid Sequence↗

PubMed1995

Graves' disease in HTLV-I carriers.

Three carriers of human T-lymphotropic virus type I (HTLV-I) with Graves' disease are reported. All three cases were complicated with uveitis, and one also showed chronic arthropathy. Anti-HLTV-I antibody was found in the serum by the particle agglutination method and western blotting, and HTLV-I proviral DNA was detected in peripheral lymphocytes by the polymerase chain reaction and Southern blotting. HTLV-I is a causal agent of adult T-cell leukemia and HTLV-I associated myelopathy/tropical spastic paraparesis, and is believed to be related to the pathogenesis of diseases such as chronic arthropathy, uveitis, chronic bronchoalveolitis, and Sjögren's syndrome. On the other hand, retrovirus infection is considered to cause autoimmune diseases. Thus, the pathogenesis of Graves' disease in the present patients might be associated with HTLV-I infection.

Aged↗

PubMed1995

Effect of hyperthermia on cyclin B expression in a human glioblastoma cell line.

Effects of hyperthermia on the cell kinetics of glioblastoma cells were investigated using flow cytometry. Pulse-labeling with 5-bromodeoxyuridine (BUdR) and chasing of the labeled cells revealed temporary accumulation of the labeled cells in G2M phase and a reduction of DNA synthesis. The level of cyclin B rises rapidly in G2 phase and falls at the end of mitosis in normal cycling cells. Cyclin B binds to p34cdc2, resulting in histone kinase activity which is necessary for the initiation of mitosis. The amount of p34cdc2 remains constant throughout the cell cycle. The level of cyclin B was measured using an anti-cyclin B antibody and flow cytometry in order to investigate the cause of the G2 accumulation induced by hyperthermia. A low level of cyclin B, in comparison with that of normal cycling cells, persisted for more than 3 h after hyperthermia. These results indicate that the temporary accumulation of cells in G2M phase after hyperthermia may be caused, at least in part, by an insufficient level of cyclin B.

Antibodies, Monoclonal↗

PubMed1995

Role of hepatocytes in direct clearance of lipopolysaccharide in rats.

BACKGROUND & AIMS: The liver is the clearance organ for lipopolysaccharide (LPS). The aim of this study was to investigate the biliary excretion of LPS using fluorescein isothiocyanate (FITC)-labeled LPS. METHODS: After FITC-LPS was injected intravenously into rats, the cellular localization of fluorescence in the liver was examined and the biliary excretion of fluorescence was measured. The effects of gadolinium chloride, a blocker of Kupffer cells, and colchicine, an inhibitor of microtubules, on the biliary excretion of fluorescence was investigated, and bile was analyzed using high-performance liquid chromatography. RESULTS: Laser scanning confocal microscopy showed that fluorescence was taken up by hepatocytes 5 minutes after injection of FITC-LPS into the portal vein. When FITC-LPS was injected into the portal vein, fluorescence was rapidly secreted into bile, peaking at 20 minutes, and 25.1% of the injected dose appeared in bile within 60 minutes. When the same dose of FITC-LPS was injected into the tail vein, 15.8% appeared in bile within 60 minutes. Chromatography showed that FITC-LPS was excreted into bile in an unchanged form over a period of 20 minutes after injection. Colchicine significantly reduced the biliary excretion of fluorescence, but gadolinium chloride had no effect. CONCLUSIONS: LPS was directly and effectively processed by hepatocytes and secreted into the bile canalicular system via a microtubule-dependent vesicular pathway.

Animals↗

PubMed1995

The significance of PCNA and p53 protein in some oral tumors.

The expression of PCNA and p53 protein was evaluated in a total of 75 cases of benign and malignant lesions of the oral cavity, comprising 50 squamous cell carcinomas (SCCs), 14 leukoplakias, and 11 pleomorphic adenomas. The DNA histogram of 20 SCCs was measured by flow cytometry. p53-positive cells were frequently seen in SCCs, but were rare in leukoplakias and pleomorphic adenomas. The PCNA labeling index (LI) was higher in SCCs than in other benign lesions. The expression rate of p53 protein was markedly elevated in SCCs obtained from smoking patients, when compared to nonsmoking patients. DNA ploidy did not show a close relationship with PCNA and p53 expression. The mean value of PCNA LI for 22 cases carrying positive p53 protein was 52.3%, which was higher than that of p53 protein negative cases (35.7%). The Kaplan-Meier survival curve of the patients who were negative for p53 was significantly more favorable than for patients who were positive for p53 (P < 0.01, Cox-Mantel test). These results suggest that PCNA and p53 LI are markers for the malignant potential of the oral mucosa, and are a useful indicator suggesting a poor prognosis.

Actuarial Analysis↗

PubMed1995

A fluorescence in situ hybridization (FISH) analysis with centromere-specific DNA probes of chromosomes 3 and 17 in pleomorphic adenomas and adenoid cystic carcinomas.

Aberrations of chromosomes 3 and 17 were studied by FISH using centromere-specific DNA probes in 11 salivary adenoid cystic carcinomas (ACC) and 8 salivary pleomorphic adenomas (PA), with 3 lymph nodes as controls. Two hybridized signals were detected in 92.8 +/- 2.7% of controls, 73.2 +/- 7.0% of PA and 66.8 +/- 7.9% of ACC cells for chromosome 3, and in 90.4 +/- 2.3% of controls, 59.5 +/- 25.0% of PA and 44.8 +/- 20.2% of ACC for chromosome 17. More than 3 hybridized signals, which indicate polysomy, were observed in 3.1% of controls, 15.5% of PA and 22.9% of ACC cells for chromosome 3, and in 1.2% of controls, 10.3% of PA and 23.1% of ACC cells for chromosome 17. A single hybridized signal was much more frequent for chromosome 17 than for chromosome 3. These findings suggest that polysomy of both chromosomes occurs during the development of salivary gland tumors, and its frequency is increased in adenoid cystic carcinoma as compared to pleomorphic adenoma. In addition, monosomy of chromosome 17 could possibly be significant in salivary gland tumors.

Adenoma, Pleomorphic↗

PubMed1995

Phosphate excretion during 24 h of hypoxia in conscious rats.

The objective of this study was to investigate renal phosphate excretion during 24 h of hypoxia in conscious rats fed by total parenteral nutrition. Wistar rats weighing 190 g were exposed to hypoxia (inspired oxygen fraction = 0.10) or normoxia (inspired oxygen fraction = 0.21) for 24 h in a normobaric chamber. Renal clearance and hormonal studies were performed. The results showed a greater fractional excretion of phosphate (5.37 +/- 0.07%, P < 0.05) and hypophosphataemia (7.40 +/- 0.12 mg dL-1, P < 0.01) in hypoxic rats (n = 10) than in normoxic rats (n = 13; 3.50 +/- 0.37% and 8.02 +/- 0.16 mg dL-1, respectively). In addition, during hypoxia there was a significant decrease in the excretion of urinary adenosine 3',5'-cyclic monophosphate per glomerular filtrate (2.97 +/- 1.27 nmol dL-1, P < 0.005), a parameter of the renal action of parathyroid hormone, and a stable level of serum parathyroid hormone (10.2 +/- 2.6 ng mL-1) (cf. normoxia: 8.57 +/- 0.70 nmol dL-1 and 8.0 +/- 1.7 ng mL-1, respectively). However, creatinine clearance and the renal adenosine triphosphate level, both of which affect adenosine 3',5'-cyclic monophosphate excretion, were not different between the two groups. These data suggest that exposure of conscious rats to 24 h of hypoxia causes renal hyporesponsiveness to physiological levels of parathyroid hormone, which is manifested as a decrease in adenosine 3',5'-cyclic monophosphate excretion. Phosphaturia is not a direct net effect of hypoxia and secondary hypocapnia on renal phosphate transport, which is known to be regulated by parathyroid hormone through adenosine 3',5'-cyclic monophosphate.

Animals↗

PubMed1995

The structure-activity relationship between synthetic butylidenephthalide derivatives regarding the competence and progression of inhibition in primary cultures proliferation of mouse aorta smooth muscle cells.

The inhibitory effects of synthetic butylidenephthalide (BP) derivatives on 10% fetal bovine serum-stimulated proliferation were assayed by measuring the proliferative cell number at an interval of 12 h in primary cultures of mouse aorta smooth muscle cells (SMC). Their potencies for the anti-proliferation effect were in the order BP-42 (4,5-dihydroxy BP) > BP-92 (4,5-dihydroxy butylphthalide) > BP-97 (6,7-dihydroxy-3-(3-bromo-1-octenyl)-phthalide) > BP-82 (6,7-dihydroxy BP) > BP-86 (5,6-dihydroxy BP) > BP-87 (4,5,6-trihydroxy BP) > BP-85 (4,7-dihydroxy BP) > BP-84 (5,7-dihydroxy BP) > BP-4C3 (4-methoxy propylphthalide) > BP-7 (4-hydroxy BP) > BP-40 (4,5-dimethoxy butylphthalide) > BP-5C3 (4-hydroxy propylphthalide). We divided these anti-proliferative effects into anti-competence and anti-progression effects by using a convenient assay. BP-42 had the greatest potency in used phthalides for competence inhibition of the SMC proliferation. BP-92 had small potency for competence inhibition. BP-97 had greater potency for competence inhibition than BP-82. These results demonstrated that the anti-proliferative effect of BP-42 was greatest in used phthalides in primary cultures of vascular SMC. The 4,5-dihydroxy group and 3-butylidene or 3-(3-bromo-1-octenyl) group in these synthetic BP derivatives contributed to the anti-competence effect on SMC. BP-42 may become a prototype of an anti-atherosclerotic drug.

Animals↗

PubMed1995

Activation by alpha 1-adrenergic agonists of the progression phase in the proliferation of primary cultures of smooth muscle cells in mouse and rat aorta.

The effects of catecholamines on the competence and progression phases in the proliferation of vascular smooth muscle cells (SMCs) in mouse and rat were investigated in primary cultures: alpha,beta-Adrenergic agonists such as epinephrine and norepinephrine, and the alpha-adrenergic agonist, phenylephrine, stimulated proliferation of primary cultured SMCs, whereas the alpha 2-adrenergic agonist, clonidine, and beta-adrenergic agonist, isoproterenol, did not. The stimulating effect of epinephrine was maximal at 0.54 microM and was then decreased at higher concentrations. The alpha-adrenergic antagonist, phentolamine, and alpha 1-adrenergic antagonist, prazosin, inhibited epinephrine-induced SMC proliferation, while the alpha 2-adrenergic antagonist, yohimbine, and beta-adrenergic antagonist, propranolol, did not. In primary cultured and synchronized SMCs at the G0 phase, norepinephrine accelerated the rate of SMC proliferation, but did not change the starting time of DNA synthesis and proliferation. These results show that catecholamines activate the progression phase in primary cultured aortic SMCs alpha 1-adrenergic receptors.

Adrenergic alpha-Agonists↗

PubMed1995

Anti-competence effects of synthetic phthalide derivatives on platelet-derived growth factor-induced DNA synthesis in primary cultures of rat aorta smooth muscle cells.

The inhibitory effect of 3-butylidene-4,5-dihydroxyphthalide (BP-42) on platelet derived growth factor (PDGF)-BB-induced DNA synthesis was investigated in synchronized smooth muscle cells (SMC) in primary culture of rat aorta. BP-42 (0.3-3 micrograms/ml) inhibited the PDGF-BB (30 ng/ml)-stimulated [3H]thymidine incorporation of the SMC in a concentration-dependent manner. BP-42 inhibited both the competence and progression phases of [3H]thymidine incorporation induced by PDGF-BB. Using the competence assay, BP-42 (0.3-10 micrograms/ml) delayed PDGF-BB (30 ng/ml)-accelerated starting time of [3H]thymidine incorporation in a concentration-dependent manner, confirming that BP-42 inhibited PDGF-BB-induced competence phase of DNA synthesis of SMC. BP-42 (1-10 micrograms/ml) also delayed basic fibroblast growth factor (bFGF: 30 ng/ml)-accelerated starting time of [3H]thymidine incorporation. The inhibitory potency of BP-42 for the competence action of PDGF-BB was similar to that for the action of bFGF. BP-421 (3-heptylidene-4,5-dihydroxyphthalide) and BP-422 (3-benzylidene-4,5-dihydroxyphthalide) had 3-fold greater inhibitory potencies than BP-42 for the PDGF-BB-induced competence activity. These results demonstrated that BP-42 inhibited PDGF-BB-induced competence activity of DNA synthesis in primary cultured SMC of rat aorta via a common signal transduction mechanism with bFGF. BP-421 and BP-422 were more potent inhibitors for the competence activity, suggesting that they may become a prototype of new anti-atherosclerotic drugs.

Animals↗

PubMed1995

Effect of vasopressin V1- and V2-receptor stimulation on blood pressure in DOCA-salt hypertensive rats.

We recently reported that stimulation of the arginine vasopressin (AVP) V1-receptor enhanced the pressor response in spontaneously hypertensive rats (SHR). In the present study, we investigated acute changes in systolic blood pressure (SBP) and heart rate (HR) after intravenous injections of AVP, OPC-21268 (a V1-receptor antagonist), and OPC-31260 (a V2-receptor antagonist), in anesthetized DOCA-salt hypertensive rats (DOCA) and age-matched sham-operated Wistar rats (control) to determine whether the pressor effect is specific to SHR or is present in other hypertensive animal models. SBP increased significantly in DOCA rats 9 min after injection of AVP 5 ng/kg without a concomitant increase in HR. Neither OPC-21268 3mg/kg nor OPC-31260 3mg/kg caused significant changes in SBP or HR. SBP tended to increase when AVP was administered after injection of OPC-31260. HR increased significantly 15 min after the combined treatment with OPC-31260 and AVP in DOCA rats compared with control rats. SBP did not change significantly when AVP was administered after injection of OPC-21268 in DOCA or control rats, but HR decreased significantly from 1 to 4 min after injection of AVP in DOCA rats. Our results suggest that V1-receptor stimulation does not enhance the pressor response in the DOCA rat, which is a model of volume-dependent hypertension, suggesting that the AVP system, especially V1-receptor, is not as important in the development or maintenance of hypertension in DOCA rats as in SHR.

Animals↗

PubMed1995

Enhanced pressor response in spontaneously hypertensive rats induced by stimulation of vasopressin-V1 receptors.

To elucidate the effect of the arginine vasopressin (AVP) system in vivo, especially V1 and V2 activity, on blood pressure, we measured the acute changes in blood pressure and heart rate after AVP, OPC-21,268 (a V1 receptor antagonist), and OPC-31,260 (a V2 receptor antagonist) were injected intravenously in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at the age of 15 weeks. Compared with the control period, single injection of AVP 5 ng/kg significantly increased systolic blood pressure in WKY rats without a concomitant increase in heart rate, but there was no significant increase in blood pressure in SHR. In contrast, single injection of either OPC-21,268 3 mg/kg or OPC-31,260 3 mg/kg did not affect blood pressure or heart rate in either SHR or WKY rats. Injection of AVP after the administration of OPC-31,260 induced a greater increase in blood pressure in SHR than in WKY rats, whereas injection of AVP after the administration of OPC-21,268 did not induce any clear increase in blood pressure in SHR or WKY rats. These results suggest that SHR have enhanced pressor activity mediated by V1 receptors and that this increase may be due to an increase in their number. In conclusion, enhancement of V1 activity may contribute to the development of high blood pressure in SHR.

Animals↗

PubMed1995

Relapsing polychondritis associated with subclinical Sjögren's syndrome and phlegmon of the neck.

A 25-year-old woman, diagnosed with Sjögren's syndrome at age 20, presented with painful edema of her left neck. Three days later, she additionally complained of bilateral auricular pain, and her nasal cartilage was tender to palpation. She was diagnosed as having phlegmon on the basis of her neck findings. Anti-human cartilage antibodies were demonstrated by indirect immunofluorescence, and the diagnosis of relapsing polychondritis was established. The patient was administered antibiotics and a non-steroidal anti-inflammatory drug, and her symptoms gradually improved. Relapsing polychondritis is one of the possible complications of autoimmune diseases, and infection might be a precipitating factor for this disease.

Adult↗

PubMed1995

[A battery model of the eyeball to calculate standing potential of the eye].

Variation of the resting potential caused by eye movements was analyzed by applying a battery model to the eyeball. A formula that gives the potential between the inner canthus and the outer canthus of the eye was derived on the basis of the electric theory in electromagnetics, on the assumption that the eyeball was floating in a homogeneous conductor. The variations of the resting potentials were represented using the distance from the center of the eyeball to the potential detecting position and the deflection angle of the position with respect to the optical axis of the eyeball. To verify the validity of the formula, the variation of the resting potential caused by the various amplitudes of bilaterally symmetrical eye movements were measured. The calculated results were found to be in good agreement with the experimental ones.

Electrooculography↗

PubMed1995

Role of cytoskeleton and acidification of endocytic compartment in asialoglycoprotein metabolism in isolated rat hepatocyte couplets.

The process of receptor-mediated endocytosis is common to a variety of species and cell types. One of the best characterized receptor-ligand systems is the hepatocyte receptor for asialoglycoproteins. We investigated the morphological features of the uptake and intracellular transport of gold-conjugated asialofetuin in isolated rat hepatocyte couplets. We assessed the effects of colchicine, lumicolchicine, cytochalasin B, and chloroquine on the uptake and intracellular transport of asialoglycoproteins. Isolated rat hepatocyte couplets were incubated with gold-conjugated asialofetuin, and transmission electron micrographs of these cells were analyzed to determine the density and distribution of gold particles in the peripheral and pericanalicular areas. Results were analyzed morphometrically. Colchicine significantly inhibited the uptake and intracellular transport of asialoglycoproteins, but did not affect membrane fusion of endocytic compartments in the peripheral area. Lumicolchicine and cytochalasin B had minimal effects on these processes. Chloroquine inhibited the uptake of asialoglycoproteins, but did not affect the intracellular transport of asialoglycoproteins. Results suggest that the microtubule is essential for intracellular movement of endocytosed asialoglycoproteins and receptor recycling, and that endocytic structures in the peripheral regions can fuse in the absence of intact microtubules. We also found that uptake and intracellular transport of asialoglycoproteins were independent of the microfilaments, and the pH gradient in endocytic compartments was important in receptor-mediated endocytosis of asialoglycoproteins.

Acids↗

PubMed1995

Mechanisms of adaptation to hypoxia in energy metabolism in rats.

BACKGROUND: Oxygen supply to the tissues is needed in the early postoperative period to meet the energy requirements for maintaining cellular activity. This study was done to investigate energy metabolism in rats during hypoxia in order to determine the mechanism underlying the acclimatization of energy production to oxygen depletion. STUDY DESIGN: Wistar rats were divided into two experimental groups: hypoxic and normoxic, which were supplied with 10 and 21 percent oxygen for 20 hours, respectively. At the end of the experiment, blood and hepatic tissue samples were taken to determine endocrine and metabolic responses to hypoxia. Energy expenditure during hypoxia was also evaluated. RESULTS: Hypoxia resulted in marked increases in blood concentrations of triglycerides, free fatty acids, catecholamines, and corticosterone. Hypoxia marked by depressed resting energy expenditure and respiratory quotient, and produced a stable hepatic adenosine triphosphate (ATP) level. The cytosolic redox state, represented by the ratio of lactate to pyruvate concentrations in the liver, and the arterial ketone body ratio declined during hypoxia. With hypoxia, an increase in alanine and decreases in glutamine and glutamate levels in the liver were observed. CONCLUSIONS: These results suggest that hypoxia depresses energy expenditure, which leads to a normoxic level of hepatic ATP. Fat is a main metabolic fuel during hypoxia. Hypoxia leads to the development of a pathway that shunts pyruvate and glutamate to alanine and alpha-ketoglutarate, allowing efficient energy production.

Adaptation, Physiological↗