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Regulating GLUT4 Sorting into the In...

Foley, Kevin Patrick.

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Regulating GLUT4 Sorting into the Insulin-Responsive Compartment in Muscle Cells.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Regulating GLUT4 Sorting into the Insulin-Responsive Compartment in Muscle Cells./
作者:	Foley, Kevin Patrick.
面頁冊數:	182 p.
附註:	Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.
Contained By:	Dissertation Abstracts International76-10B(E).
標題:	Cellular biology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3704135
ISBN:	9781321763362

Regulating GLUT4 Sorting into the Insulin-Responsive Compartment in Muscle Cells.
Foley, Kevin Patrick.

Regulating GLUT4 Sorting into the Insulin-Responsive Compartment in Muscle Cells. - 182 p.

Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2014.

Skeletal muscle and adipose tissue serve as the major storage sites for glucose, and insulin is the major signal for glucose uptake into these tissues. Glucose transporter 4 (GLUT4) is responsible for the uptake of glucose into muscle and adipose tissues. This protein constitutively recycles between the plasma membrane and intracellular depots. Under resting conditions, most GLUT4 molecules are maintained in intracellular compartments. Insulin shifts this dynamic equilibrium towards the plasma membrane by recruiting a fraction of GLUT4 to the plasma membrane from insulin responsive vesicles. However, steady-state measurements of GLUT4 localization have failed to reveal the subcellular localization of these vesicles or how GLUT4 is sorted to them.

ISBN: 9781321763362Subjects--Topical Terms:

3172791
Cellular biology.

Regulating GLUT4 Sorting into the Insulin-Responsive Compartment in Muscle Cells.
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245 1 0 $a Regulating GLUT4 Sorting into the Insulin-Responsive Compartment in Muscle Cells.
300 $a 182 p.
500 $a Source: Dissertation Abstracts International, Volume: 76-10(E), Section: B.
500 $a Adviser: Amira Klip.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2014.
520 $a Skeletal muscle and adipose tissue serve as the major storage sites for glucose, and insulin is the major signal for glucose uptake into these tissues. Glucose transporter 4 (GLUT4) is responsible for the uptake of glucose into muscle and adipose tissues. This protein constitutively recycles between the plasma membrane and intracellular depots. Under resting conditions, most GLUT4 molecules are maintained in intracellular compartments. Insulin shifts this dynamic equilibrium towards the plasma membrane by recruiting a fraction of GLUT4 to the plasma membrane from insulin responsive vesicles. However, steady-state measurements of GLUT4 localization have failed to reveal the subcellular localization of these vesicles or how GLUT4 is sorted to them.
520 $a By analyzing the sorting of GLUT4 as it internalizes from the cell surface, advances may be made in revealing how GLUT4 acquires insulin-responsiveness and the intracellular location in which this occurs. In L6 myoblasts stably expressing myc-tagged GLUT4, surface-labelled GLUT4 myc that internalizes for 30 min accumulates in a Syntaxin-6 (Stx6)-positive perinuclear compartment and displays insulin-responsive exocytosis. Although Stx6 knockdown does not alter the perinuclear accumulation of internalized GLUT4myc, it does inhibit by &sim;50% the ability of internalized GLUT4myc to undergo insulin-responsive exocytosis. These results suggest that the Stx6-positive perinuclear compartment consists of at least two sub-compartments---one that serves as a dynamic retention compartment and one that is insulin-responsive. Microtubule disruption with nocodazole prevents internalized GLUT4myc from reaching the Stx6-positive perinuclear compartment and undergoing insulin-responsive exocytosis. Removing nocodazole allows internalized GLUT4myc to re-acquire insulin-responsive exocytosis in correlation with recovering its accumulation in the Stx6-positive perinuclear compartment. C2-ceramide, which induces insulin resistance, inhibits GLUT4 sorting into the Stx6-positive perinuclear compartment and insulin-responsive exocytosis independently of affecting insulin-stimulated Akt. I propose that internalized GLUT4 must sort through a Stx6-positive compartment that is normally perinuclear as a preamble to acquiring insulin-responsiveness.
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710 2 $a University of Toronto (Canada). $b Biochemistry. $3 3180039
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790 $a 0779
791 $a Ph.D.
792 $a 2014
793 $a English
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