• Title/Summary/Keyword: Brain, metabolism

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A Journey to Understand Glucose Homeostasis: Starting from Rat Glucose Transporter Type 2 Promoter Cloning to Hyperglycemia

  • Ahn, Yong Ho
    • Diabetes and Metabolism Journal
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    • v.42 no.6
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    • pp.465-471
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    • 2018
  • My professional journey to understand the glucose homeostasis began in the 1990s, starting from cloning of the promoter region of glucose transporter type 2 (GLUT2) gene that led us to establish research foundation of my group. When I was a graduate student, I simply thought that hyperglycemia, a typical clinical manifestation of type 2 diabetes mellitus (T2DM), could be caused by a defect in the glucose transport system in the body. Thus, if a molecular mechanism controlling glucose transport system could be understood, treatment of T2DM could be possible. In the early 70s, hyperglycemia was thought to develop primarily due to a defect in the muscle and adipose tissue; thus, muscle/adipose tissue type glucose transporter (GLUT4) became a major research interest in the diabetology. However, glucose utilization occurs not only in muscle/adipose tissue but also in liver and brain. Thus, I was interested in the hepatic glucose transport system, where glucose storage and release are the most actively occurring.

Long-Term Clinical Course of a Korean Patient with Chronic Neuropathic (type III) Gaucher Disease

  • Lee, Jun Hwa
    • Journal of Interdisciplinary Genomics
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    • v.1 no.2
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    • pp.15-18
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    • 2019
  • Gaucher disease (GD) is an autosomal recessive inborn error of metabolism resulting from a deficiency in ${\beta}$-glucocerebrosidase (GBA) activity that leads to the accumulation of glucocerebroside in macrophages in multiple organs, such as the bone marrow, liver, spleen, and brain. GD can be classified into three clinical types: type 1 (non-neuropathic form, OMIM #230800); type II (acute neuropathic form, OMIM #230900); and type III (chronic neuropathic form, OMIM #231000). Type III is the subacute form of neuropathic GD. The best available treatment for GD is long-term enzyme (imiglucerase) replacement therapy (ERT) performed every two weeks. This report describes the long-term clinical course of a patient with type III GD who was treated with ERT for 18 years.

Wilson Disease Comorbid with Hereditary Sensory Autonomic Neuropathy Type IV and Gitelman Syndrome

  • Kim, Ju Young;Park, Sung Sup;Yang, Hye Ran
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.22 no.4
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    • pp.392-399
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    • 2019
  • Wilson disease a rare autosomal recessive inherited disorder of copper metabolism, is characterized by excessive deposition of copper in the liver, brain, and other tissues. Wilson disease is often fatal if it is not recognized early and treated when it is symptomatic. Gitelman syndrome is also an autosomal recessive kidney disorder characterized by low blood levels of potassium and magnesium, decreased excretion of calcium in the urine, and elevated blood pH. Hereditary sensory autonomic neuropathy type IV (HSAN-IV), a very rare condition that presents in infancy, is characterized by anhidrosis, absence of pain sensation, and self-mutilation. It is usually accompanied by developmental delay and mental retardation. We report a case of Wilson disease manifested as fulminant hepatitis, acute pancreatitis, and acute kidney injury in a 15-year-old boy comorbid with HSAN-IV and Gitelman syndrome. Such concurrence of three genetic diseases is an extremely rare case.

Quantitative Analysis of Metabolism for Brain Hippocampus based on Multi-modality Image Registration (다중모달리티 영상정합기반 뇌 해마영역 기능대사 정량분석)

  • Kim, Min-Jeong;Choi, Yoo-Joo;Kim, Myoung-Hee
    • Proceedings of the Korea Information Processing Society Conference
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    • 2004.05a
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    • pp.1645-1648
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    • 2004
  • 해마를 비롯하여, 뇌 기능과 밀접한 관련을 가지는 뇌 하위조직의 분석에 대한 최근 연구로 MR 영상 등의 해부학적 영상으로부터의 볼륨 추출, 형상 복원, 대칭성 비교 등을 들 수 있다. 이러한 연구들은 뇌의 해부학적 정보에만 의존함으로써 관심영역에 대한 신진대사 등의 분석에 한계를 가진다. 본 논문에서는 뇌 해마영역에 대하여 해부학적, 기능적 특성의 동시 분석이 가능한 프로시저를 제안한다. 먼저 해부학적 영상과 기능적 영상의 다중모달리티 영상정합을 수행하고 이를 기반으로 해마 SPECT 볼륨이 추출되며, 나아가 체적 측정 및 강도 분포 등의 정량분석을 수행함으로써 해부학적 영역의 기능정보에 대한 직관적이며 객관적인 분석이 가능하도록 하였다.

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Different Metabolic Patterns of Parkinsonism: Analysed by Statistical Parametric Mapping (통계적 파라미터를 이용한 Parkinsonism의 Metabolic pattern 분석)

  • 주라형;김재승;최보영;문대혁;서태석
    • Progress in Medical Physics
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    • v.14 no.2
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    • pp.108-123
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    • 2003
  • The purpose of this study is to evaluate the contribution of $^{18}$ F-FDG brain PET in the differentiating Idiopathic parkinson's diesease (IPD), progressive supranuclear palsy (PSP), and multiple system atrophy (MSA). We studied 24 patients with parkinsonism : 8 patients (mean age 67.9$\pm$10.7 y: M/F : 3/5) with IPD, 9 patients (57.9$\pm$9.2 y : M/F : 4/5) with MSA and 7 patients (67.6$\pm$4.8 y : M/F 3/4) with PSP. All patients with parkinsonism and 22 age-matched normal controls underwent $^{18}$ F FDG PET in 3D mode after the injection of 370 MBq $^{118}$ F FDG. The patients with IPD, MSh and PSP were compared with a normal control group by a two-sided t-test of SPM99 (uncorrected P<0.001, extent threshold>100 voxel). All three parkinsonism groups, showed significant hypometabolism in the cerebral neocortex compared to the normal control group. However, the three groups displayed different metabolism in the subcortical structure, brain stem, and cerebellum. In IPD, there was no significant hypometabolism in the putamen, brain stem and cerebellum. However, MSA patients showed significant hypometabolism in the striatum, pons, and cerebellum compared to the normal controls and IPD patients. In addition, PSP showed significant hypometabolism in the caudate nuclei, the thalamus, midbrain, and the cingulate gyrus compared to the normal controls, the IPD, and MSA groups (IPD vs Normal sensitivity/specificity : 75%/l00%, MSA vs Normal sensitivity/specificity :100%/87%, PSP vs Normal sensitivity/specificity : 86%/94%). Our results show that the regional metabolism of IPD, MSA, and PSP is different mainly in the striatum, thalamus, brain stem and cerebellum. An assessment of the $^{18}$ F-FDG PET scan images using SPM may be a useful adjunct to a clinical examination in making a differential diagnosis of Parkinsonism.

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A Critical Evaluation of the Correlation Between Biomarkers of Folate and Vitamin $B_{12}$ in Nutritional Homocysteinemia (엽산과 비타민 $B_{12}$ 결핍에 의한 호모시스테인혈증 흰쥐의 조직내 비타민 지표간의 상관관계 분석)

  • Min, Hye-Sun;Kim, Mi-Sook
    • Journal of Nutrition and Health
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    • v.42 no.5
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    • pp.423-433
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    • 2009
  • Folate and vitamin $B_{12}$ are essential cofactors for homocysteine (Hcy) metabolism. Homocysteinemia has been related with cardiovascular and neurodegenerative disease. We examined the effect of folate and/or vitamin $B_{12}$ deficiency on biomarkers of one carbon metabolism in blood, liver and brain, and analyzed the correlation between vitamin biomarkers in mild and moderate homocysteinemia. In this study, Sprague-Dawley male rats (5 groups, n = 10) were fed folatesufficient diet (FS), folate-deficient diet (FD) with 0 or 3 g homocystine (FSH and FDH), and folate-/vitamin $B_{12}$-deficient diet with 3 g homocystine (FDHCD) for 8 weeks. The FDH diet induced mild homocysteinemia (plasma Hcy 17.41 ${\pm}$ 1.94 nmol/mL) and the FDHCD diet induced moderate homocysteinemia (plasma Hcy 44.13 ${\pm}$ 2.65 nmol/mL), respectively. Although liver and brain folate levels were significantly lower compared with those values of rats fed FS or FSH (p < 0.001, p < 0.01 respectively), there were no significant differences in folate levels in liver and brain among the rats fed FD, FDH and FDHCD diet. However, rats fed FDHCD showed higher plasma folate levels (126.5 ${\pm}$ 9.6 nmol/L) compared with rats fed FD and FDH (21.1 ${\pm}$ 1.4 nmol/L, 22.0 ${\pm}$ 2.2 nmol/L)(p < 0.001), which is the feature of "ethyl-folate trap"by vitamin $B_{12}$ deficiency. Plasma Hcy was correlated with hepatic folate (r = -0.641, p < 0.01) but not with plasma folate or brain folate in this experimental condition. However, as we eliminated FDHCD group during correlation test, plasma Hcy was correlated with plasma folate (r = -0.581, p < 0.01), hepatic folate (r = -0.684, p < 0.01) and brain folate (r = -0.321, p < 0.05). Hepatic S-adenosylmethionine (SAM) level was lower in rats fed FD, FDH and FDHCD than in rats fed FS and FSH (p < 0.001, p < 0.001 respectively) and hepatic S-adenosylhomocysteine (SAH) level was significantly higher in those groups. The SAH level in brain was also significantly increased in rats fed FDHCD (p < 0.05). However, brain SAM level was not affected by folate and/or vitamin $B_{12}$ deficiency. This result suggests that dietary folate- and vitamin B12-deficiency may inhibit methylation in brain by increasing SAH rather than decreasing SAM level, which may be closely associated with impaired cognitive function in nutritional homocysteinemia.

Evaluation of Database Comparison Methods for 18F-FDG Brain PET/CT (18F-FDG Brain PET/CT 검사를 위한 데이터 비교 방법의 평가)

  • Do, Yong Ho;Lee, Hong Jae;Kim, Jin Eui
    • The Korean Journal of Nuclear Medicine Technology
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    • v.19 no.1
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    • pp.62-66
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    • 2015
  • Purpose Various database comparison methods(DCM) are used for analyzing functional neuro-imaging. It is possible to statistically evaluate decreased or increased metabolism of abnormal patient's brain by comparing with asymptomatic controls in DCM. And results of DCM are additionally used for easily explaining defect region. The aim of this study was to evaluate usefulness of statistical parametric mapping(SPM) and scenium. Materials and Methods Data of 15 patients($62.02{\pm}15.03year$) underwent $^{18}F-FDG$ brain PET/CT were collected and analyzed. Biograph TruePoint 40 with TrueV, (Siemens) was used as a PET/CT scanner. Scenium(version 4.0) in Syngo.via(version VA30A) and SPM99 were applied for statistical evaluation. Consistency between PET reading and result of DCM were evaluated by 5 nuclear medicine physicians through a questionnaire survey. SUV and SD changes were evaluated by changing iteration, gaussian filter and matrix size in scenium. And average required time for generating result of SPM99 and scenium was compared by 3 medical technologists. Results Consistency from the result of SPM99 and scenium showed 84% and 92.4% compare to PET reading. When iteration 4, FWHM 8 and matrix size 168, SUV and SD were decreased by 0.59%, 8.73%, 4.69%, 20.38% and 0.88%, 8.25% respectively compare to routine parameter(iteration 8, FWHM 2 and matrix size 336) of scenium. Average required time of SPM99 and Scenium took 282 seconds and 116 seconds to generate result. Conclusion Results of SPM99 and Scenium showed high consistency compare to PET reading. Various parameters can be controled by user when using SPM. However, normal database needs to be acquired. And it takes significant amount of time and effort for the first set up. On the other hand, Scenium provides normal database even though modifiable parameters are limited. Therefore, more informations could be provided for brain PET/CT if properly understanding and selecting each DCM.

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Metabolic Adjustment of Lactate Dehydrogenase Isozymes to a Change in Dissolved Oxygen in Bluegill (Lepomis macrochirus) (파랑볼우럭(Lepomis macrochirus)에서 용존산소량의 변화에 대한 젖산탈수소효소 동위효소들의 대사조절)

  • Ku, Bora;Cho, Sung Kyu;Yum, Jung Joo
    • Journal of Life Science
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    • v.31 no.12
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    • pp.1066-1071
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    • 2021
  • The aim of this study was to examine the metabolic adjustment of lactate dehydrogenase (EC 1.1.1.27, LDH) isozymes to a change in dissolved oxygen (DO) in bluegill (Lepomis macrochirus). After bluegills were adapted to a constant environment in an aquarium, the DO was changed to investigate the activity of LDH isozyme and the relative ratio of subunits A, B, and C for each tissue. When the DO was decreased from 18 ppm to 6 ppm, LDH in skeletal muscle, heart, and brain tissues recovered to the level of control activity within 12, 12, and 6 hr, respectively. LDH activity changed in accordance with a change in DO. The compensation was performed rapidly and is thought to be an important function of LDH in enabling bluegills to adapt to their environment. In bluegill heart, eye, and brain tissues, the relative ratio of subunit A increased and showed a tendency to recover similarly to the subunit ratio of control groups up to 12 hr. It is thought that the anaerobic metabolism using subunit A was increased in the initial stage when DO was changed. In addition, the results revealed that subunit C was more similar to subunit A than subunit B. In bluegills, subunits A and C of LDH seem to be evolutionarily similar. LDH isozymes, mainly containing subunits A and C, are likely responsible for the function of pyruvate reductase, which plays a role in making the bluegill adapt to a hypoxic environment through anaerobic metabolism.

Epigenetic Responses Programmed by Prenatal Stress : $F_1$ Male Rat Model (출생 전 스트레스에 의해 프로그램된 후생학적 반응 : $F_1$ 수컷 흰쥐 모델)

  • Lee, Sung-Ho
    • Development and Reproduction
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    • v.12 no.2
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    • pp.117-124
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    • 2008
  • The efficient strategies to cope with unpredictable and/or harmful environmental changes have been developed by every organism in order to ensure its survival and continuity of it's own species. As a results, all living things on earth maintain dynamically internal stability via a process termed 'homeostasis' among physiological parameters despite of external environment changes. Stress is an emotional and physical response to threat homeostasis. Stress may have not only transient but rather permanent effect on the organism; recent evidence clearly show that prenatal stress could organize or imprint permanently physiological systems without any change in genetic codes, a process known as 'epigenetic programming'. In this review, a series of reproduction-associated events occurred in prenatally stressed male rats such as alteration in the structure of sexually dimorphic brain regions, modification of neurotransmitter metabolism, changes in reproductive endocrine status, and finally, disorders of sexual behavior will be introduced. The fetal brain is highly sensitive to prenatal programming and glucocorticoids in particular have powerful brain-programming properties. The chronic hyperactivation of fetal brain by maternal stress-induced glucocorticoid input will provide new program via increasing the neuroplasticities. This 'increased neuroplasticities' will be the basis for the 'increased phenotypic plasticities' rendering the organism's better adaptation to environmental challenges. In conclusion, organism who experienced 'harsh' environment in his fetal life seems to give up a certain portion of reproductive competence to make good chance of survival in his future life by epigenetic (re)programming.

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2-DG Autoradiographic Imaging of Brain Activity Patterns by Electroacupuncture Stimulation in Awake Rats (전침자극(電針刺戟)에 의한 흰쥐 중추신경계(中樞神經系)내 대사활성(代謝活性) 변화(變化)의 영상화(映像化) 연구(硏究))

  • Sohn, Young-Joo;Won, Ran;Jung, Hyuk-Sang;Kim, Yong-Suk;Park, Young-Bae;Sohn, Nak-Won
    • Journal of Acupuncture Research
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    • v.18 no.3
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    • pp.56-68
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    • 2001
  • Objective : Functional brain mapping study on acupuncture stimulation using the [14C]2-deoxyglucose([14C]2-DG) autoradiography provides quantitative data and visualized pathway in central nervous system(CNS). We aimed to investigate the neural pathway and spatial distribution of metabolic activity elicited in CNS on electroacupuncture stimulation using [14C]2-DG autoradiography. Methods : The study were divided into three groups by stimulation times. 45-mins stimulation group according to Sokoloffs method, 5-mins stimulation group according to Duncun's method, and 15-mins stimulation group. ;A venous catheter was equipped into right jugular vein. The rats (Sprague-Dawley rats, 230-260g) were kept fastened loosely on a holding platform without anesthesia. Electroacupuncture stimulation (5 ms, 2 Hz, 1~3 mA) were applied on the left Zusanli (ST36) acupoint and [14C]2-DG ($25{\mu}Ci/rat$) injection was performed through the catheter. After sacrifice, the brain and the spinal cord were made to sections for film image. The film images were digitalized as the isotope concentration based upon comparison of optical densities with that of the standards and normalized by the optical density of corpus callosum. Results : 1. 15-mins stimulation group was most effective among 3 experiments. 2. On 15-mins stimulation group, medial geniculate nucleus, intetpeduncular nucleus intermedius, ventral periolivary nucleus, caudal periolivary nucleus, medial superior olive, lateral paragigantocellular nucleus, including hypothalamic arcuate nucleus were increased by more than 25% (at least, p<0.05) by electroacupuncture stimulation. 3. Especially, the metabolism in hypothalamic arcuate nucleus was increased by 90% (p<0.05). 4. The fact that arcuate nucleus of hypothalamus might play a role of interconnection area between ascending and descending pathway of acupuncture stimulation was demonstrated visually. Conclusions : Advanced study on electroacupuncture stimulation elicited significant increase of metabolic activity in various nuclei of hypothalamus will provide the important experimental basis in research of the relationship between electroacupuncture stimulation and internal visceral functions.

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