Effects of Fiber Type, Contraction, Exercise, and Diet on Skeletal Muscle Signaling Proteins and Glucose Transport.
dc.contributor.author | Castorena, Carlos Michel | en_US |
dc.date.accessioned | 2014-01-16T20:43:52Z | |
dc.date.available | 2014-01-16T20:43:52Z | |
dc.date.issued | 2013 | en_US |
dc.date.submitted | 2013 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/102486 | |
dc.description.abstract | This thesis focused on the regulation of glucose uptake in rat skeletal muscle. Skeletal muscle plays a central role in the regulation of whole body glucose homeostasis. Because skeletal muscle is a heterogeneous tissue, muscles are often categorized by fiber type (myosin heavy chain, MHC, expression). MHC expression was determined at both the muscle tissue and single fiber levels, along with measurement of the abundance of multiple proteins relevant to glucose uptake, including the GLUT4 glucose transporter and Akt substrate of 160kDa (AS160). Key measurements included contraction-stimulated glucose uptake by single fibers from epitrochlearis muscles, and insulin-stimulated glucose uptake by whole epitrochlearis muscles from both normal rats fed low fat diet (LFD) and insulin-resistant rats (fed high fat diet, HFD, for 2 weeks). Novel results included: 1) MHC-related differences in GLUT4, but not AS160, protein abundance were found in whole muscles and single fibers; 2) despite a four-fold range of GLUT4 abundance among fiber types, contraction-stimulated glucose uptake did not differ by MHC-expression; 3) immediately post-exercise, insulin-independent glucose uptake and phosphorylation of AMP-associated protein kinase and AS160 were not different for LFD versus HFD groups; 4) improved insulin-stimulated glucose uptake 3 hours post-exercise in both LFD and HFD groups was associated with greater pAS160 (phosphorylated AS160) with unaltered GLUT4 abundance and MHC-expression; and 5) values for both insulin-stimulated glucose uptake and pAS160 post-exercise were greater for LFD versus HFD rats. Earlier studies suggested that muscle insulin resistance with HFD results from increased insulin receptor substrate-1 serine phosphorylation (pIRS-1Ser), thereby inhibiting proximal insulin signaling (including tyrosine phosphorylation of the insulin receptor, IRS-1-associated phosphatidyl-3-kinase, and Akt activity), but exercise did not increase these proximal signaling steps in either diet-group. Greater pIRS-1Ser is believed to result from elevated diacylglycerol and ceramides leading to activation of serine kinases, including JNK, but exercise did not attenuate pIRS-1Ser, diacylglycerol, ceramides or pJNK. Results of this thesis indicate that exercise did not appear to act on several processes that are commonly linked to insulin resistance, suggesting that future experiments seeking to identify mechanisms for improved insulin-simulated glucose uptake post-exercise should focus on distal signaling steps regulating pAS160. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | Exercise and Insulin Sensitivity | en_US |
dc.subject | Skeletal Muscle Glucose Uptake | en_US |
dc.title | Effects of Fiber Type, Contraction, Exercise, and Diet on Skeletal Muscle Signaling Proteins and Glucose Transport. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Kinesiology | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.contributor.committeemember | Cartee, Gregory Dean | en_US |
dc.contributor.committeemember | Burant, Charles | en_US |
dc.contributor.committeemember | Bodary, Peter F. | en_US |
dc.contributor.committeemember | Horowitz, Jeffrey F. | en_US |
dc.subject.hlbsecondlevel | Kinesiology and Sports | en_US |
dc.subject.hlbsecondlevel | Physiology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/102486/1/ccastore_1.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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