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

Involvement of protein kinase C in s...

Itani, Samar Ibrahim.

FindBook

Google Book

Amazon

博客來

Involvement of protein kinase C in skeletal muscle insulin resistance and type 2 diabetes.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Involvement of protein kinase C in skeletal muscle insulin resistance and type 2 diabetes./
作者:	Itani, Samar Ibrahim.
面頁冊數:	170 p.
附註:	Director: G. Lynis Dohm.
Contained By:	Dissertation Abstracts International61-02B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9962491
ISBN:	0599665483

Involvement of protein kinase C in skeletal muscle insulin resistance and type 2 diabetes.
Itani, Samar Ibrahim.

Involvement of protein kinase C in skeletal muscle insulin resistance and type 2 diabetes. - 170 p.

Director: G. Lynis Dohm.

Thesis (Ph.D.)--East Carolina University, 2000.

There is evidence to support the involvement of protein kinase C (PKC) in skeletal muscle insulin resistance and type 2 diabetes. We and others have shown that insulin-stimulated glucose transport was impaired in insulin resistant skeletal muscle. Previous data from our laboratory showed that insulin receptors were excessively phosphorylated on serine/threonine residues and insulin-stimulated tyrosine kinase activity of the insulin receptor was depressed in muscle from insulin resistant patients. In addition, studies from our laboratory suggest the possible involvement of PKC in impaired insulin action in insulin resistant muscle. To investigate this possibility, we compared the protein expression and activity of various PKC isoforms in muscle from obese, insulin resistant and lean, insulin responsive patients. Particulate PKC β content/activity was increased in the basal (unincubated) and insulin-stimulated state in insulin resistant muscle. This suggests the possible involvement of this isoform in skeletal muscle insulin resistance. PKC β, &thetas;, and δ translocated to the particulate fraction and were activated in response to insulin in insulin resistant but not insulin responsive muscle. This data suggests that PKC in insulin resistant muscle was more sensitive to insulin stimulation and that PKC β, &thetas;, and δ may modulate the tyrosine kinase activity of the insulin receptor. Our data show that PKC β, &thetas;, δ, μ, ϵ, and ζ modulate the insulin receptor and are not part of the insulin transduction pathway in human skeletal muscle. To show a cause and effect relationship between PKC β and insulin resistance, transgenic mice with PKC β knocked out (muscle and heart) or overexpressed (heart) were used. Knocking out PKC β significantly increased insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 in gastrocnemius muscle and heart. In contrast, overexpressing PKC β significantly reduced insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 in the heart. Finally, we show that PKC &thetas; protein content/activity was increased in muscle from obese, diabetic patients compared to muscle from obese, nondiabetic controls. This suggests the possible involvement of this PKC isoform in diabetes. From our data we conclude that muscle insulin resistance is caused by elevated PKC activity, which phosphorylates and inactivates the insulin receptor.

ISBN: 0599665483Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

Involvement of protein kinase C in skeletal muscle insulin resistance and type 2 diabetes.
LDR:03399nam 2200277 a 45 001 929408
005 20110427
008 110427s2000 eng d
020 $a 0599665483
035 $a (UnM)AAI9962491
035 $a AAI9962491
040 $a UnM $c UnM
100 1 $a Itani, Samar Ibrahim. $3 1252894
245 1 0 $a Involvement of protein kinase C in skeletal muscle insulin resistance and type 2 diabetes.
300 $a 170 p.
500 $a Director: G. Lynis Dohm.
500 $a Source: Dissertation Abstracts International, Volume: 61-02, Section: B, page: 0839.
502 $a Thesis (Ph.D.)--East Carolina University, 2000.
520 $a There is evidence to support the involvement of protein kinase C (PKC) in skeletal muscle insulin resistance and type 2 diabetes. We and others have shown that insulin-stimulated glucose transport was impaired in insulin resistant skeletal muscle. Previous data from our laboratory showed that insulin receptors were excessively phosphorylated on serine/threonine residues and insulin-stimulated tyrosine kinase activity of the insulin receptor was depressed in muscle from insulin resistant patients. In addition, studies from our laboratory suggest the possible involvement of PKC in impaired insulin action in insulin resistant muscle. To investigate this possibility, we compared the protein expression and activity of various PKC isoforms in muscle from obese, insulin resistant and lean, insulin responsive patients. Particulate PKC β content/activity was increased in the basal (unincubated) and insulin-stimulated state in insulin resistant muscle. This suggests the possible involvement of this isoform in skeletal muscle insulin resistance. PKC β, &thetas;, and δ translocated to the particulate fraction and were activated in response to insulin in insulin resistant but not insulin responsive muscle. This data suggests that PKC in insulin resistant muscle was more sensitive to insulin stimulation and that PKC β, &thetas;, and δ may modulate the tyrosine kinase activity of the insulin receptor. Our data show that PKC β, &thetas;, δ, μ, ϵ, and ζ modulate the insulin receptor and are not part of the insulin transduction pathway in human skeletal muscle. To show a cause and effect relationship between PKC β and insulin resistance, transgenic mice with PKC β knocked out (muscle and heart) or overexpressed (heart) were used. Knocking out PKC β significantly increased insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 in gastrocnemius muscle and heart. In contrast, overexpressing PKC β significantly reduced insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 in the heart. Finally, we show that PKC &thetas; protein content/activity was increased in muscle from obese, diabetic patients compared to muscle from obese, nondiabetic controls. This suggests the possible involvement of this PKC isoform in diabetes. From our data we conclude that muscle insulin resistance is caused by elevated PKC activity, which phosphorylates and inactivates the insulin receptor.
590 $a School code: 0600.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Health Sciences, Pathology. $3 1017854
690 $a 0487
690 $a 0571
710 2 0 $a East Carolina University. $3 1019505
773 0 $t Dissertation Abstracts International $g 61-02B.
790 $a 0600
790 1 0 $a Dohm, G. Lynis, $e advisor
791 $a Ph.D.
792 $a 2000
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=9962491