東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

Insulin resistance and cardiac metab...

Qi, Dake.

FindBook

Google Book

Amazon

博客來

Insulin resistance and cardiac metabolism.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Insulin resistance and cardiac metabolism./
作者:	Qi, Dake.
面頁冊數:	136 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7028.
Contained By:	Dissertation Abstracts International67-12B.
標題:	Health Sciences, Pharmacology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR20070
ISBN:	9780494200704

Insulin resistance and cardiac metabolism.
Qi, Dake.

Insulin resistance and cardiac metabolism. - 136 p.

Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7028.

Thesis (Ph.D.)--The University of British Columbia (Canada), 2006.

Insulin resistance, clinically defined as a defect of insulin action, is closely linked to an increased incidence of cardiovascular disease. Although metabolic abnormalities have been known to initiate heart failure, the relationship between insulin resistance and cardiac metabolism is currently unclear. In my initial study, acute effects of dexamethasone (DEX) on rat cardiac metabolism were examined. A single dose of DEX leads to whole-body insulin resistance. Moreover, in hearts from these animals, glucose oxidation is compromised due to augmentation of pyruvate dehydrogenase kinase (PDK4), whereas amplification of LPL increases lipoprotein triglyceride clearance, likely providing the heart with excessive FA that are then stored as intracellular triglyceride. In the heart, AMP-activated protein kinase (AMPK) is an important regulator of both lipid and carbohydrate metabolism. Once stimulated, AMPK inhibits acetyl-CoA carboxylase (ACC), which catalyzes the conversion of acetyl-CoA to malonyl-CoA. This decreases malonyl-CoA, minimizes its inhibition of FA oxidation, and FA utilization increases. Cardiac palmitate oxidation in DEX treated hearts was higher compared to control, and was coupled to increased phosphorylation of ACC280. Measurement of polyunsaturated FAs demonstrated a drop in linoleic and gamma linolenic acid, with an increase in arachidonic acid after acute DEX injection. Given the detrimental effects of compromised glucose utilization, high FA oxidation, TG storage, and arachidonic acid accumulation, our data suggests that these effects of DEX on cardiac metabolism could explain the increased cardiovascular risk associated with chronic glucocorticoid therapy. Although a small portion of the patient population exhibits glucocorticoid-induced insulin resistance, the primary cause of this syndrome is excessive circulating FA, usually associated with obesity. The concluding study in my PhD project was to explore the effects of acute high FA induced insulin resistance on LPL at the coronary lumen. Acute IL infusion augments plasma LPL, and this was associated with reduced LPL activity at the coronary lumen, but increased enzyme within endothelial cells and subendothelial space. It is likely that these effects are a consequence of FA releasing LPL from apical endothelial HSPG, in addition to augmenting endothelial heparanase, which facilitates myocyte HSPG cleavage and transfer of LPL towards the coronary lumen. These data suggest that the control of cardiac LPL is complex, and insulin resistance, in the presence or absence of high FA have differential effect on the enzyme.

ISBN: 9780494200704Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Insulin resistance and cardiac metabolism.
LDR:03389nam 2200241 a 45 001 964101
005 20110901
008 110901s2006 eng d
020 $a 9780494200704
035 $a (UMI)AAINR20070
035 $a AAINR20070
040 $a UMI $c UMI
100 1 $a Qi, Dake. $3 1287171
245 1 0 $a Insulin resistance and cardiac metabolism.
300 $a 136 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-12, Section: B, page: 7028.
502 $a Thesis (Ph.D.)--The University of British Columbia (Canada), 2006.
520 $a Insulin resistance, clinically defined as a defect of insulin action, is closely linked to an increased incidence of cardiovascular disease. Although metabolic abnormalities have been known to initiate heart failure, the relationship between insulin resistance and cardiac metabolism is currently unclear. In my initial study, acute effects of dexamethasone (DEX) on rat cardiac metabolism were examined. A single dose of DEX leads to whole-body insulin resistance. Moreover, in hearts from these animals, glucose oxidation is compromised due to augmentation of pyruvate dehydrogenase kinase (PDK4), whereas amplification of LPL increases lipoprotein triglyceride clearance, likely providing the heart with excessive FA that are then stored as intracellular triglyceride. In the heart, AMP-activated protein kinase (AMPK) is an important regulator of both lipid and carbohydrate metabolism. Once stimulated, AMPK inhibits acetyl-CoA carboxylase (ACC), which catalyzes the conversion of acetyl-CoA to malonyl-CoA. This decreases malonyl-CoA, minimizes its inhibition of FA oxidation, and FA utilization increases. Cardiac palmitate oxidation in DEX treated hearts was higher compared to control, and was coupled to increased phosphorylation of ACC280. Measurement of polyunsaturated FAs demonstrated a drop in linoleic and gamma linolenic acid, with an increase in arachidonic acid after acute DEX injection. Given the detrimental effects of compromised glucose utilization, high FA oxidation, TG storage, and arachidonic acid accumulation, our data suggests that these effects of DEX on cardiac metabolism could explain the increased cardiovascular risk associated with chronic glucocorticoid therapy. Although a small portion of the patient population exhibits glucocorticoid-induced insulin resistance, the primary cause of this syndrome is excessive circulating FA, usually associated with obesity. The concluding study in my PhD project was to explore the effects of acute high FA induced insulin resistance on LPL at the coronary lumen. Acute IL infusion augments plasma LPL, and this was associated with reduced LPL activity at the coronary lumen, but increased enzyme within endothelial cells and subendothelial space. It is likely that these effects are a consequence of FA releasing LPL from apical endothelial HSPG, in addition to augmenting endothelial heparanase, which facilitates myocyte HSPG cleavage and transfer of LPL towards the coronary lumen. These data suggest that the control of cardiac LPL is complex, and insulin resistance, in the presence or absence of high FA have differential effect on the enzyme.
590 $a School code: 2500.
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
710 2 0 $a The University of British Columbia (Canada). $3 626643
773 0 $t Dissertation Abstracts International $g 67-12B.
790 $a 2500
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR20070