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Mitochondrial energetics in insulin ...

Lefort, Natalie Rose.

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Mitochondrial energetics in insulin resistance.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Mitochondrial energetics in insulin resistance./
Author:	Lefort, Natalie Rose.
Description:	232 p.
Notes:	Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2871.
Contained By:	Dissertation Abstracts International71-05B.
Subject:	Biology, Physiology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407153
ISBN:	9781109748604

Mitochondrial energetics in insulin resistance.
Lefort, Natalie Rose.

Mitochondrial energetics in insulin resistance. - 232 p.

Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2871.

Thesis (Ph.D.)--Arizona State University, 2010.

The contribution of mitochondrial deficiencies and/or adaptations to skeletal muscle insulin resistance was investigated. Firstly, mitochondria were isolated from human vastus lateralis muscle from three lean, healthy male individuals. The proteome of these highly functional, well coupled mitochondria was characterized using high-performance liquid chromatography (HPLC) followed by electron spray ionization tandem mass spectrometry (ESI-MS/MS). Eight hundred and twenty-three unique proteins were identified, of which 487 were previously characterized mitochondrial proteins. The majority of the protein members of the citric acid cycle and the fatty acid oxidation pathway were detected, as well as proteins in the electron transport chain (83% of subunits), in the mitoribosome, involved in protein import and related to cell death. Secondly, mitochondria isolated from lean, insulin-sensitive (I/S) and obese, insulin-resistant (I/R) individuals were probed for differences in oxidative capacity and superoxide (O2 ·-; indirectly via hydrogen peroxide) production rates. A semi-quantative proteomics approach using normalized spectral abundance factors was applied to top-ten mass spectrometric data of these isolated mitochondria. Mitochondria from I/R individuals generated respiration rates similar to those from I/S individuals in response to combinations of pyruvate, malate, glutamate, succinate and palmitoyl-DL-carnitine. However, higher superoxide production rates were measured in the mitochondria from I/R individuals. Comparison of the relative abundance of proteins in the mitochondria] preparations showed that specific subunits of complex I, enzymes involved in the oxidation of branched-chain amino acids and carnitine palmitoyltransferase 1B were less abundant in the mitochondria from I/R muscle. Lastly, mitochondrial complex V (ATP synthase) was studied in order to determine potential differences in the phosphorylation pattern of the beta subunit in response to insulin stimulation and in the face of insulin resistance. In particular, threonine 213 (Thr213) and tyrosine 361 (Tyr361) residues were hyper-phosphorylated in the basal state in I/R individuals. Following insulin stimulation, Tyr361 phosphorylation was increased in I/S, but not I/R individuals.

ISBN: 9781109748604Subjects--Topical Terms:

1017816
Biology, Physiology.

Mitochondrial energetics in insulin resistance.
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020 $a 9781109748604
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100 1 $a Lefort, Natalie Rose. $3 1683866
245 1 0 $a Mitochondrial energetics in insulin resistance.
300 $a 232 p.
500 $a Source: Dissertation Abstracts International, Volume: 71-05, Section: B, page: 2871.
500 $a Adviser: Lawrence Mandarino.
502 $a Thesis (Ph.D.)--Arizona State University, 2010.
520 $a The contribution of mitochondrial deficiencies and/or adaptations to skeletal muscle insulin resistance was investigated. Firstly, mitochondria were isolated from human vastus lateralis muscle from three lean, healthy male individuals. The proteome of these highly functional, well coupled mitochondria was characterized using high-performance liquid chromatography (HPLC) followed by electron spray ionization tandem mass spectrometry (ESI-MS/MS). Eight hundred and twenty-three unique proteins were identified, of which 487 were previously characterized mitochondrial proteins. The majority of the protein members of the citric acid cycle and the fatty acid oxidation pathway were detected, as well as proteins in the electron transport chain (83% of subunits), in the mitoribosome, involved in protein import and related to cell death. Secondly, mitochondria isolated from lean, insulin-sensitive (I/S) and obese, insulin-resistant (I/R) individuals were probed for differences in oxidative capacity and superoxide (O2 ·-; indirectly via hydrogen peroxide) production rates. A semi-quantative proteomics approach using normalized spectral abundance factors was applied to top-ten mass spectrometric data of these isolated mitochondria. Mitochondria from I/R individuals generated respiration rates similar to those from I/S individuals in response to combinations of pyruvate, malate, glutamate, succinate and palmitoyl-DL-carnitine. However, higher superoxide production rates were measured in the mitochondria from I/R individuals. Comparison of the relative abundance of proteins in the mitochondria] preparations showed that specific subunits of complex I, enzymes involved in the oxidation of branched-chain amino acids and carnitine palmitoyltransferase 1B were less abundant in the mitochondria from I/R muscle. Lastly, mitochondrial complex V (ATP synthase) was studied in order to determine potential differences in the phosphorylation pattern of the beta subunit in response to insulin stimulation and in the face of insulin resistance. In particular, threonine 213 (Thr213) and tyrosine 361 (Tyr361) residues were hyper-phosphorylated in the basal state in I/R individuals. Following insulin stimulation, Tyr361 phosphorylation was increased in I/S, but not I/R individuals.
520 $a In conclusion, these studies suggest that the mitochondrial pool of I/R skeletal muscle, although exhibiting normal oxidative capacity, presents specific alterations, such as a higher potential for ROS production, lower abundance of key mitochondrial proteins per mitochondrial mass and differential phosphorylation patterns of ATPase.
590 $a School code: 0010.
650 4 $a Biology, Physiology. $3 1017816
650 4 $a Biology, Cell. $3 1017686
650 4 $a Chemistry, Biochemistry. $3 1017722
690 $a 0379
690 $a 0487
690 $a 0719
710 2 $a Arizona State University. $3 1017445
773 0 $t Dissertation Abstracts International $g 71-05B.
790 1 0 $a Mandarino, Lawrence, $e advisor
790 $a 0010
791 $a Ph.D.
792 $a 2010
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3407153