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Biomedical subjects

T Shimazu

Publications and source records attributed to T Shimazu.

At least 127 records · Page 7Linked to original sources
PubMed1994

Effects of wortmannin on increased glucose transport by insulin and norepinephrine in primary culture of brown adipocytes.

The effects of wortmannin, a selective inhibitor of phosphatidylinositol (PI) 3-kinase, on increases in glucose transport activity induced by insulin and norepinephrine (NE) have been studied in primary culture of brown adipocytes. Both insulin and NE produced 2- to 3-fold increase in 2-deoxy-D-[3H]glucose (2-DG) transport into cultured brown adipocytes. The effect of insulin was dependent upon translocation of the muscle/adipocyte glucose transporter (GLUT4) from microsome to plasma membranes. In contrast, NE did not affect the subcellular distribution of GLUT4. When wortmannin was added to the medium before stimulation with insulin, the increase in glucose transport and translocation of GLUT4 were completely abolished. On the other hand, NE-induced increase in glucose transport was resistant to wortmannin. These results indicate that PI 3-kinase plays a critical role on insulin-induced translocation of GLUT4, but that this pathway is not involved in the increase in glucose transport by NE in brown adipocytes.

Adipose Tissue, Brown↗
PubMed1994

Regulatory mechanism of the ventromedial hypothalamus in enhancing glucose uptake in skeletal muscles.

To evaluate roles of the sympathetic nervous system in enhancing glucose uptake in skeletal muscles in response to electrical stimulation of the ventromedial hypothalamic nucleus (VMH), the effects of guanethidine treatment and adrenal demedullation on the response were examined in rats anesthetized and injected with muscle relaxant, pancuronium bromide. Pretreatment with guanethidine effectively suppressed the increase in the rate constant of glucose uptake, measured by the 2-deoxy-D-[3H]glucose method, in skeletal muscles upon VMH stimulation. However, bilateral adrenodemedullation had no significant effect. These results suggest that the VMH is intimately concerned in the regulation of glucose uptake in skeletal muscles through intermediation of the sympathetic nerves.

Adrenal Medulla↗
PubMed1994

Reduced hepatic release of apoprotein B after enteral nutrition in rats.

To investigate the effects of enteral and parenteral alimentation on VLDL release from the liver, a lipid-free liquid nutriment was continuously administered to free-moving rats via the oral cavity (oral group), stomach (enteral group) or superior caval vein (parenteral group). After 1-week of nutrition, the plasma VLDL concentrations were significantly lowered in the enterally-fed group. By immunoblotting assay using a specific antiserum, plasma contents of both apoprotein B-100 and B-48, the major components of rat apoprotein B, were found to be decreased in the enteral group, whereas only that of apoprotein B-48 was reduced in the parenteral group as compared with the oral group. Sucrose gradient centrifugation of the lipid droplets in the liver from the enteral group showed an increase of the free-triacylglycerol fraction with a concomitant increase of the apoprotein B-48-rich triacylglycerol fraction. These results suggest that enteral nutrition causes triacylglycerol accumulation in the liver, at least in part by impairment of lipoprotein release from the liver.

Animals↗
PubMed1994

Dexamethasone induces the GLUT4 glucose transporter, and responses of glucose transport to norepinephrine and insulin in primary cultures of brown adipocytes.

Glucose uptake into brown adipose tissue is enhanced directly by norepinephrine released from the sympathetic nerves. In the present study, we tried to establish culture conditions for brown adipocytes which are favorable for investigation of this unique glucose transport. Stromal-vascular cells isolated from the interscapular brown adipose tissue of newborn rats differentiated into brown adipocytes expressing the uncoupling protein, when the cells were maintained on collagen-coated dishes. These cells, however, did not show an increase in 2-[3H]deoxyglucose transport in response to insulin or norepinephrine, nor did they exhibit expression of the GLUT4 glucose transporter, whereas GLUT1 was present, as judged on Western blotting. Pre-treatment of confluent cells with dexamethasone induced a response of glucose transport to either insulin or norepinephrine, and the expression of GLUT4, together with notable accumulation of lipid droplets. The induction of GLUT4 expression by dexamethasone was dose-dependent and potentiated by insulin. These results indicate that treatment of cultured brown adipocytes with dexamethasone makes it feasible to analyze the mechanism underlying the enhancement of glucose transport induced by norepinephrine.

Adipocytes↗
PubMed1993

Nucleotide sequence of the Mn-stabilizing protein gene of the thermophilic cyanobacterium Synechococcus elongatus.

The nucleotide sequence of the psbO gene encoding the extrinsic 33 kDa protein (the Mn-stabilizing protein) from the thermophilic cyanobacterium Synechococcus elongatus was determined. The deduced amino acid sequence consisted of 272 residues; 26 for the signal peptide and 246 for the mature protein. The amino acid sequences of nine proteolytic peptides from the isolated protein completely agreed with the deduced amino acid sequence. Several unique variations of amino acids were found in the primary structure, of which some may be related to the high thermostability of the protein.

Amino Acid Sequence↗
PubMed1993

Structural, functional and evolutionary implications of the three-dimensional crystal structure of murine interferon-beta.

The crystal structure of recombinant murine interferon-beta as elucidated by Senda et al. (Proc. Jap. Acad. 66B: 77-80 (1990); EMBO J. 11: 3193-3201 (1992)) appears to represent the basic structural framework of all Type I interferons including interferons-beta and all subtypes of interferons-alpha of various mammalian origin. Now the huge accumulated data on the structure-activity relationship of Type I interferons using various chemical and genetic techniques can be systematically evaluated in terms of the three-dimensional structure. Structural comparison with other cytokines, for which three-dimensional structures have been established, including interferon-gamma and considerations on the evolution of cytokines and cytokine receptors are also given.

Amino Acid Sequence↗
PubMed1993

Recovery from postoperative hypothermia predicts survival in extensively burned patients.

To clarify the cause of postoperative hypothermia in extensively burned patients, factors affecting postoperative hypothermia were studied in 16 extensively burned adult patients (8 survivors and 8 nonsurvivors) with a burn index greater than 35. Body temperature was monitored continuously in either the urinary bladder or rectum. Hypothermia of less than 35 degrees C occurred in 89% (66 of 74) of the total operations performed in these 16 patients. The rate of temperature rise (RTR) was significantly lower in nonsurvivors (0.4 +/- 0.2 degrees C/h) than in survivors (1.7 +/- 0.9 degrees C/h; p < 0.001). Continuous indirect calorimetry performed in seven patients (four survivors and three nonsurvivors) demonstrated that RTR was determined primarily by heat production. The measured energy expenditure reached only 1.7 +/- 0.2 times the basal energy expenditure during rewarming in nonsurvivors, whereas it was 2.7 +/- 0.9 times the basal energy expenditure in survivors (p < 0.01). Surprisingly, in nonsurvivors, the RTR was significantly decreased even during the first 2 weeks. These findings suggest that those who cannot generate heat well in postoperative hypothermia are unable to produce the additional energy required to overcome sepsis.

Adult↗
PubMed1993

Laterality of air volume in the lungs long after blunt chest trauma.

To clarify a cause of the persistent decrease in lung capacity seen several years after blunt chest trauma, 17 patients with blunt chest trauma (10 with unilateral lung contusion, 7 with bilateral lung contusions; 11 of these with unilateral flail chest) inflicted 1 to 6 years previously and 10 normal volunteers (control) were studied. Lung air volumes (AV) were measured by spirometry (AVsp) and by computed tomographic (CT) scan (AVCT = AVCT.Rt+AVCT.Lt) under the same conditions. Hemithoracic spaces were also calculated by CT scan. The average AVsp in patients (76% +/- 8%) was lower than in the controls (98% +/- 5%). AVCT was consistent with AVsp in all the measurements. %AVCT.Rt and %AVCT.Lt, which were adjusted by the ratio of AVCT.Rt to AVCT.Lt in the controls, decreased significantly in unilateral contused lungs (71% +/- 8%). Fifty-eight percent of contused lungs showed small fibrous changes on the CT scans. The ratio of the hemithoracic space on the flail chest side to the opposite side was 0.95 +/- 0.05. These results suggest that the persistent decrease in AV long after blunt chest trauma might be caused by a constriction of contused lung resulting from fibrous changes.

Adolescent↗
PubMed1993

Effect of a beta 3-adrenergic agonist, BRL35135A, on glucose uptake in rat skeletal muscle in vivo and in vitro.

The effects of the beta 3-agonist, BRL35135A, on glucose uptake in the peripheral tissues of the rat, including skeletal muscle, were studied using the 2-[3H]deoxyglucose method in anaesthetized adult animals. Intravenous infusion of the beta 3-agonist dose-dependently increased the rate constant of glucose uptake in three types of skeletal muscle, brown adipose tissue, white adipose tissue, heart and diaphragm, but not in the brain, spleen or lung. Although infusion of the beta 3-agonist did not change the plasma concentration of glucose appreciably, it caused an increase in the plasma concentration of insulin when given at more than 25 micrograms/kg per h. To ascertain whether the effect of the beta 3-agonist on glucose uptake in skeletal muscle is mediated by insulin, glucose uptake into soleus muscle isolated from young rats was also measured in vitro using different concentrations of the beta 3-agonist. The beta 3-agonist BRL37344 (an active metabolite of BRL35135A) significantly increased glucose transport in a dose-dependent manner, with maximum stimulation at 100 pmol/l. These results demonstrate that glucose uptake in skeletal muscle can be enhanced independently of the action of insulin, probably through the mediation of beta 3-adrenoceptors present in the tissue.

Adipose Tissue↗
PubMed1993

Altered lipid metabolism during enteral or parenteral nutrition in rats: comparison with oral feeding.

To investigate the effects of different routes of alimentation on lipid metabolism, lipid-free nutrients with the same amount of energy and composition were continuously administered via the oral cavity (oral group), directly to the stomach (enteral group), or into the superior caval vein (parenteral group) of unrestrained rats. The body weight gain 1 week after continuous nutrition was greater in enteral and parenteral groups than in the orally-fed group. In comparison with the orally-fed group, the enterally-fed group had significantly greater liver and retroperitoneal adipose tissue weights and hepatic lipid content, whereas the parenterally-fed group produced similar changes to those in the enteral group without significant accumulation of hepatic lipid. The rate of fatty acid synthesis after 1 week of alimentation was 3-fold higher in the liver in enterally-fed group, and approximately 10-fold higher in white adipose tissue in both enterally- and parenterally-fed groups than in orally-fed group. Plasma concentrations of catecholamines after 6 h were significantly higher in the orally-fed group than in either the enteral or parenteral group. However, plasma insulin concentrations were not significantly different among the three groups. The results indicate that lipid synthesis and its deposition in the liver and adipose tissue are greatly influenced by the route of alimentation, possibly owing to difference in the early neuro-hormonal responses to different routes of alimentation.

Animals↗
PubMed1992

Three-dimensional crystal structure of recombinant murine interferon-beta.

The crystal structure of recombinant murine interferon-beta (IFN-beta) has been solved by the multiple isomorphous replacement method and refined to an R-factor of 20.5% against 2.6 A X-ray diffraction data. The structure shows a variant of the alpha-helix bundle with a new chain-folding topology, which seems to represent a basic structural framework of all the IFN-alpha and IFN-beta molecules belonging to the type I family. Functionally important segments of the polypeptide chain, as implied through numerous gene manipulation studies carried out so far, are spatially clustered indicating the binding site(s) to the receptor(s). Comparison of the present structure with those of other alpha-helical cytokine proteins, including porcine growth hormone, interleukin 2 and interferon gamma, indicated either a topological similarity in chain folding or a similar spatial arrangement of the alpha-helices.

Amino Acid Sequence↗
PubMed1992

Alteration in sympathetic nerve activity during liver regeneration in rats after partial hepatectomy.

To determine if the sympathetic nerve has a role in liver regeneration, the alterations of tissue norepinephrine (NE) content and its turnover were measured in rats after partial hepatectomy. NE content per unit liver mass decreased progressively to about one-fourth of controls by the ninth day after partial hepatectomy. Since the total amount of NE in the whole liver did not change during nine days of liver regeneration, it was supposed that sympathetic innervation could make slower progress than proliferation of hepatocytes. Fractional turnover rate of NE was reduced transiently in regenerating liver 24-48 h after partial hepatectomy and recovered to normal 8-9 days after the operation. Such a transient reduction of NE turnover was observed specifically in the liver. These results suggest that sympathetic nerve activity of the liver is suppressed at the early stage of regeneration.

Animals↗
PubMed1992

Vanadate stimulates D-glucose transport into sarcolemmal vesicles from rat skeletal muscles.

Vanadate is known to have various insulin-like actions including activation of D-glucose uptake into the skeletal muscle and adipose tissue. In this study, we examined the effect of orthovanadate on D-glucose uptake into sarcolemmal vesicles prepared from rat hind limb skeletal muscles. In the presence of 10 mM vanadate, the initial rate of D-glucose uptake into sarcolemmal vesicles was enhanced 4-5 times above the basal value. Half-maximal concentration for this effect of vanadate was 3 mM. The D-glucose uptake was also stimulated by metavanadate, but not by selenite, selenate, or molybdate. When vanadate was removed from the vesicles by dilution and centrifugation, D-glucose uptake into the vesicles returned to the basal level, indicating that the effect of vanadate was reversible. Saturation curves showed that the Vmax value for the D-glucose uptake was enhanced more than 4-fold by 10 mM vanadate. Therefore, the activation of D-glucose uptake was due, at least in part, to a large increase in the Vmax value. These results suggest that vanadate increases the intrinsic activity (turnover number) of skeletal muscle glucose transporters in a reversible manner.

Animals↗
PubMed1992

Effects of ventromedial hypothalamic stimulation on glucose transport system in rat tissues.

Electrical stimulation of the ventromedial hypothalamus (VMH) increased the rate constant of glucose uptake in rat heart and brown adipose tissue (BAT), as measured in vivo by the 2-deoxy-D-[3H]glucose method. The increase in glucose uptake in BAT was abolished by local sympathetic denervation. To analyze the mechanism of this hypothalamic modulation, the effects of VMH stimulation and insulin treatment on the number and dissociation constant (Kd) of glucose transporters in the plasma and microsomal membranes were examined by means of [3H]cytochalasin B binding. VMH stimulation did not alter either the number or Kd value of glucose transporters in plasma and microsomal membranes prepared from heart and BAT, whereas insulin treatment increased the number of glucose transporters in the plasma membranes and decreased those in the microsomal membranes. D-Glucose transport activity was also measured with the same plasma membrane vesicles. An apparent functional activity of transporters was detected to be increased in the heart and BAT plasma membranes after VMH stimulation but not after insulin treatment. These results suggest that VMH stimulation enhances glucose utilization in heart and BAT via sympathetic innervation and that the mechanism by which VMH stimulation increases tissue glucose uptake is different from that of insulin, possibly causing an activation of glucose transporters present in the plasma membrane.

Adipose Tissue, Brown↗
PubMed1992

Effects of concentration reduction and partial replacement of paraquat by diquat on human toxicity: a clinical survey.

Paraquat poisoning was studied in 174 patients over a 12-month period when a new, low concentration paraquat product (4.5% w/v paraquat ion mixed with 4.5% w/v diquat ion; 63 cases) replaced the original high concentration paraquat product (20% w/v paraquat ion only; 111 cases). In both groups approximately 60% of the patients died from circulatory failure accompanied by multiple organ failure within a week of ingesting the products. However, a remarkable reduction in late deaths from respiratory failure was noted in the new product group (17.1% vs 6.3%). This was reflected in this group's improved survival (23.4% vs 34.9%). The improvement in survival seems to be attributable to the dilution of paraquat with diquat which seems to have a different toxicological profile to paraquat.

Blood Urea Nitrogen↗
PubMed1992

Importance of sympathetic nerves for the stimulatory effect of cold exposure on glucose utilization in brown adipose tissue.

The effects of cold exposure on glucose transport system in brown adipose tissue (BAT) and the role of sympathetic nerves in this response were studied in rats. The rate constant of glucose uptake in BAT increased 10-, 13-, and 14-fold after 6 h, 1 d, and 2 d of cold exposure, respectively, as compared with controls. After 2 d of cold exposure, the number of glucose transporters in the plasma membranes increased from 10.2 +/- 1.1 to 16.7 +/- 1.4 pmol/mg protein and the transporter number in the microsomal membranes decreased from 15.1 +/- 1.0 to 9.0 +/- 1.1 pmol/mg protein, as measured by cytochalasin B binding. However, the increase in glucose utilization in BAT preceded the recruitment of glucose transporters to the plasma membranes. Thus, the glucose utilization markedly increased 6 h after cold exposure without significant increase in the glucose transporter number. The apparent dissociation constant (Kd) for cytochalasin B was unchanged. The stimulatory effect of cold exposure on glucose utilization in BAT was prevented by sympathetic denervation. In denervated BAT, cold exposure conversely decreased the number of glucose transporters in the plasma membranes. These results indicate that: (1) cold exposure increases glucose utilization in BAT and promotes translocation of glucose transporters from the microsomes to plasma membranes; (2) the effects of cold exposure depend entirely upon sympathetic innervation of BAT; (3) the recruitment or redistribution of glucose transporters accounts only partly for the large increase in glucose utilization in BAT after acute cold exposure.

Adipose Tissue, Brown↗
PubMed1991

Inhibition of glucose production during hepatic nerve stimulation in regenerating rat liver perfused in situ. Possible involvement of gap junctions in the action of sympathetic nerves.

To explore the possible role of gap junctions in neural regulation of hepatic glucose metabolism, the effects of hepatic nerve stimulation on metabolic and hemodynamic changes were examined in normal and regenerating rat liver which was perfused in situ at constant pressure via the portal vein with a medium containing 5 mM glucose, 2 mM lactate and 0.2 mM pyruvate. 1. The content of connexin 32, a major component of gap junctions in rat liver, decreased transiently to about 25% of the control level in regenerating liver 48-72 h after partial hepatectomy and recovered to normal by the 11th day after the operation. 2. In normal liver, electrical stimulation of the hepatic nerves (10 Hz, 20 V, 2 ms) and infusion of noradrenaline (1 microM) both increased glucose and lactate output and reduced perfusion flow. 3. In early stage of regenerating liver 48 h and 72 h after partial hepatectomy, the increase in glucose output in response to nerve stimulation was almost completely inhibited, whereas the change in lactate balance was partially suppressed and the reduction of flow rate was retained. The response of glucose output to nerve stimulation recovered by the 11th day after partial hepatectomy. In contrast, exogenous application of noradrenaline increased glucose output even in the early stage of regenerating liver. 4. The increase in noradrenaline overflow during hepatic nerve stimulation in the early stage of regenerating liver was approximately the same as in normal liver. Liver glycogen was sufficiently preserved in the early stage of regenerating liver. However, noradrenaline infusion could no more increase glucose output both in normal and in regenerating livers after 24 h of fasting that depleted liver glycogen. These results suggest that the impaired effects of sympathetic nerve stimulation on glucose metabolism observed in regenerating liver are derived neither from reduced release of noradrenaline nor from depletion of liver glycogen, but rather from transient reduction of gap junctions which assist signal propagation of the nerve action through intercellular communication in rat liver.

Animals↗