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100 1 a| Kane, Daniel A.=| ^A1266932;

245 10 a| Effects of insulin sensitivity modulators on the mitochondrial fate of oxygen in skeletal muscle /c| by Daniel A. Kane.;

260 a| [Greenville, N.C.] :b| East Carolina University,c| 2010.;

300 a| 232 pages :b| illustrations, digital, PDF file;

336 a| text2| rdacontent;

337 a| computer2| rdamedia;

338 a| online resource2| rdacarrier;

500 a| Presented to the faculty of the Department of Exercise and Sport Science.;

500 a| Advisors: Ronald N. Cortright and P. Darrell Neufer.;

500 a| Title from PDF t.p. (viewed Sep. 17, 2010).;

502 b| Ph.D.c| East Carolina Universityd| 2010.;

504 a| Includes bibliographical references.;

520 3 a| Increasingly, reactive oxygen species (ROS) are implicated in the development of insulin resistance. To test the hypothesis that modulators of insulin sensitivity (i.e., metformin, ovarian sex steroids and exercise training) affect the fate of oxygen in skeletal muscle, mitochondrial H[subscript]2O[subscript]2 emission (mE[subscript]H202) and respiratory O[subscript]2 flux (JO[subscript]2) were measured in saponin-permeabilized myofibers from rodents and women. Concommitant with improved glucose tolerance, complex I-linked mE[subscript]H202, but not JO[subscript]2, was reduced in metformin-treated obese rats to rates near or below those in the lean animals. Ex vivo dose-response experiments revealed that metformin inhibits complex I-linked mE[subscript]H202 at a concentration ~2 orders of magnitude lower than that required to inhibit JO[subscript]2. To determine if estradiol or progesterone directly affect mitochondrial function, saponin-permeabilized vastus lateralis myofibers biopsied from women in the menstrual cycle follicular phase were incubated breifly in luteal phase serum concentrations of estradiol, progesterone, or both. While progesterone alone inhibited respiration, the effect was absent in the presence of estradiol. Progesterone, alone or in combination with estradiol increased complex I-linked mE[subscript]H202. Complex I-linked mE[subscript]H202 measured in permeabilized myofibers from insulin sensitive and resistant women correlated significantly with serum progesterone in these subjects. Moreover, mE[subscript]H202 was more than 80% greater in the insulin resistant women. Regular exercise is known to improve insulin sensitivity. To determine the effects of exercise training on mitochondrial function, mE[subscript]H202 and JO[subscript]2 were measured in saponin-permeabilized vastus lateralis myofibers from lean (BMI < 30) and obese (BMI > 30) women before (Pre) and after (Post) 8 weeks of exercise training (8WT = stationary cycling, 1 h/d, 5 d/w at heart rate corresponding to 70-75% VO[subscript]2). Interestingly, while Pre-Post there were no changes in JO[subscript]2 supported by multiple substrates or calculated ratios of respiratory control, there was a reduction in the potential for complex I-linked mE[subscript]H202 following training in the lean women. Altogether, the results of this project support the notion that modulators of insulin sensitivity may do so through their ability to affect complex I-linked mE[subscript]H202, but not necessarily JO[subscript]2 in skeletal muscle.;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

650 0 a| Insulin resistance.=| ^A251831;

650 0 a| Oxygen in the body.=| ^A180895;

653 a| Biology, Physiology;

700 1 a| Cortright, Ronald N.?| UNAUTHORIZED;

700 1 a| Neufer, P. Darrell.?| UNAUTHORIZED;

710 2 a| East Carolina University.b| Department of Exercise and Sport Science.?| UNAUTHORIZED;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/2812;

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Effects of insulin sensitivity modulators on the mitochondrial fate of oxygen in skeletal muscle / by Daniel A. Kane.

Author/creator	Kane, Daniel A.
Other author	Cortright, Ronald N.
Other author	Neufer, P. Darrell.
Other author	East Carolina University. Department of Exercise and Sport Science.
Format	Theses and dissertations
Publication Info	[Greenville, N.C.] : East Carolina University, 2010.
Description	232 pages : illustrations, digital, PDF file
Supplemental Content	Access via ScholarShip
Subjects	Insulin resistance. Oxygen in the body.

Summary	Increasingly, reactive oxygen species (ROS) are implicated in the development of insulin resistance. To test the hypothesis that modulators of insulin sensitivity (i.e., metformin, ovarian sex steroids and exercise training) affect the fate of oxygen in skeletal muscle, mitochondrial H[subscript]2O[subscript]2 emission (mE[subscript]H202) and respiratory O[subscript]2 flux (JO[subscript]2) were measured in saponin-permeabilized myofibers from rodents and women. Concommitant with improved glucose tolerance, complex I-linked mE[subscript]H202, but not JO[subscript]2, was reduced in metformin-treated obese rats to rates near or below those in the lean animals. Ex vivo dose-response experiments revealed that metformin inhibits complex I-linked mE[subscript]H202 at a concentration ~2 orders of magnitude lower than that required to inhibit JO[subscript]2. To determine if estradiol or progesterone directly affect mitochondrial function, saponin-permeabilized vastus lateralis myofibers biopsied from women in the menstrual cycle follicular phase were incubated breifly in luteal phase serum concentrations of estradiol, progesterone, or both. While progesterone alone inhibited respiration, the effect was absent in the presence of estradiol. Progesterone, alone or in combination with estradiol increased complex I-linked mE[subscript]H202. Complex I-linked mE[subscript]H202 measured in permeabilized myofibers from insulin sensitive and resistant women correlated significantly with serum progesterone in these subjects. Moreover, mE[subscript]H202 was more than 80% greater in the insulin resistant women. Regular exercise is known to improve insulin sensitivity. To determine the effects of exercise training on mitochondrial function, mE[subscript]H202 and JO[subscript]2 were measured in saponin-permeabilized vastus lateralis myofibers from lean (BMI < 30) and obese (BMI > 30) women before (Pre) and after (Post) 8 weeks of exercise training (8WT = stationary cycling, 1 h/d, 5 d/w at heart rate corresponding to 70-75% VO[subscript]2). Interestingly, while Pre-Post there were no changes in JO[subscript]2 supported by multiple substrates or calculated ratios of respiratory control, there was a reduction in the potential for complex I-linked mE[subscript]H202 following training in the lean women. Altogether, the results of this project support the notion that modulators of insulin sensitivity may do so through their ability to affect complex I-linked mE[subscript]H202, but not necessarily JO[subscript]2 in skeletal muscle.
General note	Presented to the faculty of the Department of Exercise and Sport Science.
General note	Advisors: Ronald N. Cortright and P. Darrell Neufer.
General note	Title from PDF t.p. (viewed Sep. 17, 2010).
Dissertation note	Ph.D. East Carolina University 2010.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

Effects of insulin sensitivity modulators on the mitochondrial fate of oxygen in skeletal muscle / by Daniel A. Kane.

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