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스트렙토조토신 유도 당뇨병 흰쥐에서 카테킨이 간, 근육 및 지방조직의 당질 및 지질대사 관련 유전자 발현에 미치는 영향

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Author(s)
이정인
Issued Date
2020
Keyword
Catechin, Diabetes mellitus, Glucose metabolism, Lipid metabolism
Abstract
ABSTRACT

Effects of catechin on gene expression of glucose and lipid metabolism-related proteins in liver, muscle and adipose tissue of streptozotocin-induced diabetic rats

Lee Jung-In
Advisor : Prof. Shin Byoung-Chul, M.D, Ph.D.
Department of Medicine,
Graduate School of Chosun University


Background : Diabetes patients continue to increase worldwide, and persistent hyperglycemia could induce diverse complications, such as diabetic nephropathy, diabetic cardiovascular complications, neuropathy, eye, and liver complications. Since diabetic complications significantly reduce the quality of life, much research is being conducted to prevent their progress. Recently, there has been a search for natural products for the prevention of diabetes and the prevention of complications. Flavonoids are found in many plants and are known to have various physiological activities such as antioxidant, anticancer and anti-inflammatory effects. Catechin, a flavonoid contained in tea, is known to have antidiabetic effects in improving hyperglycemia in vivo and in vitro.
Objective : The purpose of this study was to investigate the transcriptoms of liver, muscle and adipose tissue to observe the effects of catechin on lipid and glucose metabolism in diabetes.
Methods : Diabetes mellitus in SD rats was induced by high fat diet and streptozotocin. The experimental group was divided into control group, diabetes group and diabetes + catechin group. The control and diabetic groups received tap water as drinking water and the diabetic + catechin group received tap water containing 0.1% catechin as drinking water for 12 weeks. After 12 weeks, blood glucose, BUN and creatinine levels were measured in the blood and transcriptomes were examined in liver, soleus muscle and visceral fat. The gene expression levels of glucose metabolism-related enzymes, lipid metabolism-related enzymes and insulin signaling pathway-related proteins were compared between each experimental group.
Results : Fasting blood glucose did not change until 12 weeks in the control and diabetic groups. Fasting blood glucose in the diabetic + catechin group was decreased by 8%, 13%, 15% and 18% at 2, 4, 8 and 12 weeks, respectively, compared to the diabetic group. After 12 weeks, serum BUN levels in the diabetic + catechin group decreased by 35% and serum creatinine levels by 33%, respectively, compared to the diabetic group. Glucose metabolism-related genes in the diabetic group were decreased in liver Gck, Pdp2 and Phkb mRNA levels, and Aldob mRNA levels in soleus muscle were decreased. In diabetic group, expression of Pfkm, Eno3 and Pgam2 in visceral fat were increased and Aldob and Pklr expression was decreased. Hepatic Gck, Pdk4 and Phkb mRNA levels were increased in the diabetic + catechin group compared to the diabetic group. Hepatic tissue Acsf2 and Acss3 mRNA levels in the diabetic group were changed. The levels of Pla2g2a, Lpl, Acsf2, Acad11, and Acaa2 mRNA in soleus muscle of diabetic rats were increased and the Pld3 mRNA levels were decreased. Acacb mRNA levels were increased and
Fasn and Slc27a1 mRNA levels were decreased in diabetic visceral adipose tissue.
Compared with the diabetic group, hepatic Acaca, Acacb and Acss3 mRNA levels were increased in the diabetic+catechin group. Hepatic Insr mRNA levels of diabetic rats were decreased, muscle tissue Irs1 mRNA levels were decreased, and there was no difference in expression levels of these genes in visceral tissues. Compared with the diabetic group, hepatic insr mRNA and muscle tissue Irs1 mRNA levels were increased in the diabetic+catechin group.
CONCLUSIONS: These results suggest that catechin administration improves hyperglycemia in diabetic rats. Catechin has the effect of improving diabetic hyperglycemia, which is thought to be the result of increased expression of liver glucose metabolism related enzymes and proteins related to insulin signal transduction pathways. Further study is needed to elucidate the mechanism of action on catechin gene expression and its usefulness as a functional substance.

Key words : Catechin, Diabetes mellitus, Glucose metabolism, Lipid metabolism
Alternative Title
Effects of catechin on gene expression of glucose and lipid metabolism-related proteins in liver, muscle and adipose tissue of streptozotocin-induced diabetic rats
Alternative Author(s)
Lee, Jung-In
Department
일반대학원 의학과
Advisor
신병철
Awarded Date
2020-02
Table Of Contents
목 차

ABSTRACT ..................................X

1. 서론 ....................................1

1-1.당뇨병이란? ..................................1
1-2. 당뇨병과 포도당 대사 ........................1
1-3. 당뇨병의 원인 및 동향 .......................2
1-4. 당뇨병의 종류 ...............................2
1-5. 당뇨병 관리 .................................3
1-6. 당뇨병 합병증 ...............................4
1-7. 식물의 2차 대사산물 .........................5
1-8. 카테킨과 당뇨병 .............................7
1-9. 전사체 분석 .................................7
1-10. 연구목적 ...................................8

2. 재료 및 방법 .............................9

2-1. 실험재료 ...................................9
2-2. 실험동물 ...................................9
2-3. 시료 채취 및 검사 .........................10
2-4. 조직 전사체 검사 ..........................11
2-5. 통계처리 ..................................12

3. 결과 ....................................13

3-1.당뇨병 유도 흰쥐의 신체적 및 혈액 생화학적
소견 .......................................13
3-2. 카테킨이 당뇨병 흰쥐의 신체적 및 생화학적
소견에 미치는 영향 ........................13
3-3. 카테킨 당뇨병 흰쥐의 혈당량에 미치는
영향 ......................................14
3-4. 카테킨이 당뇨병 흰쥐의 신장손상에 미치는
영향 ......................................14
3-5. 당뇨군의 간조직 포도당대사 관련 유전자
발현의 변화 ...............................15
3-6. 당뇨군과 당뇨+카테킨군의 간 조직 포도당대사
관련 유전자 발현의 변화 ...................15
3-7. 당뇨군의 근육조직 포도당대사 관련
유전자 발현 의변화 ........................16
3-8. 당뇨군과 당뇨+카테킨군의 근육조직 포도당
대사 관련 유전자 발현의 변화 ..............16
3-9. 당뇨군의 내장지방조직 포도당대사 관련
유전자 발현의 변화 ........................17
3-10. 당뇨군과 당뇨+카테킨군의 내장지방조직 포도당
대사 관련 유전자 발현의 변화 .............17
3-11. 대조군과 당뇨군의 간 조직 지질대사 관련
유전자 발현의 변화 .......................18
3-12. 당뇨군과 당뇨+카테킨군의 간 조직 지질대사
관련 유전자 발현의 변화 ..................18
3-13. 당뇨군의 근육조직 지질대사 관련 유전자
발현의 변화 ..............................19
3-14. 당뇨군과 당뇨+카테킨군의 근육조직 지질대사
관련 유전자 발현의 변화 ..................19
3-15. 당뇨군의 내장지방조직 지질대사 관련 유전자
발현의 변화 ..............................20

3-16. 당뇨군과 당뇨+카테킨군의 내장지방조직
지질대사 관련 유전자 발현의 변화 ........20
3-17. 당뇨군의 간 조직 인슐린 신호전달경로 관련
유전자 발현의 변화 ......................21
3-18. 당뇨군과 당뇨+카테킨군의 간 조직 인슐린
신호전달경로 관련 유전자 발현의 변화 ....21
3-19. 당뇨군의 근육조직 인슐린 신호전달경로
관련 유전자 발현의 변화 .................22
3-20. 당뇨군과 당뇨+카테킨군의 근육조직 인슐린
신호전달 경로 관련 유전자 발현의 변화 ...22
3-21. 당뇨군의 내장지방조직 인슐린 신호전달 경로
관련 유전자 발현의 변화 .................22
3-22. 당뇨군과 당뇨+카테킨군의 내장지방조직
인슐린 신호전달 경로 관련 유전자 발현의
변화 ....................................23

4. 고찰 ....................................24

5. 요약 ....................................35

6. 참고문헌 ................................37
표 목 차

Table 1. Physical and biochemical parameters of
experimental animals ..................... 43

Table 2. Effect of catechin on physical and
biochemical parameters in experimental
animals ................................ 44

Table 3. Effects of catechin on blood urea
nitrogen and creatinine in blood of
diabetic rats .......................... 45

Table 4. Select liver transcripts in control
versus DM rats related to glucose
metabolism ............................. 46

Table 5. Select liver transcripts in DM versus
DM+CA rats related to glucose metabolism
....................................... 47

Table 6. Select soleus muscle transcripts in
control versus DM rats related to
glycolysis ............................. 48

Table 7. Select soleus muscle transcripts in DM
versus DM+CA rats related to glycolysis
....................................... 49
Table 8. Select visceral fat tissue transcripts
in control versus DM rats related to
glycolysis ............................. 50

Table 9. Select visceral fat tissue transcripts
in DM versus DM+CA rats related to
glycolysis ............................. 51

Table 10. Select liver transcripts in control
versus DM rats related to lipid
metabolism ............................ 52

Table 11. Select liver transcripts in DM versus
DM+CA rats related to lipid metabolism
....................................... 53

Table 12. Select soleus muscle transcripts in
control versus DM rats related to
lipid metabolism ...................... 54

Table 13. Select soleus muscle transcripts in DM
versus DM+CA rats related to lipid
metabolism ............................ 55

Table 14. Select visceral fat tissue transcripts
in control versus DM rats related to
lipid metabolism ...................... 56

Table 15. Select visceral fat tissue transcripts
in DM versus DM+CA rats related to
lipid metabolism ...................... 57

Table 16. Select liver transcripts in control
versus DM rats related to insulin
signaling ............................. 58

Table 17. Select liver transcripts in DM versus
DM+CA rats related to insulin signaling
....................................... 59

Table 18. Select soleus muscle transcripts in
control versus DM rats related to
insulin signaling ..................... 60

Table 19. Select soleus muscle transcripts in DM
versus DM+CA rats related to insulin
signaling ............................. 61

Table 20. Select visceral fat tissue transcripts
in control versus DM rats related to
insulin signaling ..................... 62

Table 21. Select visceral fat tissue transcripts
in DM versus DM+CA rats related to
insulin signaling ..................... 63


도 목 차

Fig. 1. Flavonoid structure ................. 64

Fig. 2. Chemical structure of flavonoid ...... 65
Fig. 3. Effects of catechin on fasting blood
glucose (FBG) in diabetic rats ....... 66
Degree
Doctor
Publisher
조선대학교 대학원
Citation
이정인. (2020). 스트렙토조토신 유도 당뇨병 흰쥐에서 카테킨이 간, 근육 및 지방조직의 당질 및 지질대사 관련 유전자 발현에 미치는 영향.
Type
Dissertation
URI
https://oak.chosun.ac.kr/handle/2020.oak/14158
http://chosun.dcollection.net/common/orgView/200000284343
Appears in Collections:
General Graduate School > 4. Theses(Ph.D)
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