Effects of In Vivo Exercise and In Vitro Contractile Activity on the Regulation of AS160, TBC1D1 and Glucose Transport in Rat Skeletal Muscle.
dc.contributor.author | Funai, Katsuhiko | en_US |
dc.date.accessioned | 2010-06-03T15:45:06Z | |
dc.date.available | NO_RESTRICTION | en_US |
dc.date.available | 2010-06-03T15:45:06Z | |
dc.date.issued | 2010 | en_US |
dc.date.submitted | en_US | |
dc.identifier.uri | https://hdl.handle.net/2027.42/75927 | |
dc.description.abstract | A single bout of exercise leads to an increase in insulin-independent and insulin-dependent increase in glucose transport (GT). Phosphorylation of two members of the TBC1 (tre-2/USP6, BUB2, cdc16) domain family of proteins, Akt substrate of 160 kDa (AS160, also known as TBC1D4) and TBC1D1, has been suggested to regulate the increase in GT. The purpose of the studies in this dissertation was to provide insights into the roles that AS160 or TBC1D1 phosphorylation play in the insulin-independent and insulin-dependent increases in GT after in vivo exercise or in vitro contraction using rat epitrochlearis muscle. Immediately after in vivo exercise or in vitro contraction, the insulin-independent GT was elevated concomitant with increases in the phosphorylation of AS160 and TBC1D1. However, in experiments using pharmacological inhibitors, wortmannin (inhibits phosphatidylinositol 3-kinase) or Compound C (inhibits AMP-activated protein kinase), the increased AS160 phosphorylation after in vitro contraction was uncoupled from increased GT, whereas TBC1D1 phosphorylation and insulin-independent GT consistently tracked together. Furthermore, TBC1D1 phosphorylation and GT returned to resting values 3 h post-exercise, whereas AS160 phosphorylation remained elevated. In contrast, the prolonged increase in AS160 phosphorylation, but not TBC1D1 phosphorylation, at 3 and 27 h after in vivo exercise coincided with enhanced insulin-stimulated GT. Additionally, AS160 phosphorylation and insulin-stimulated GT both reversed to resting levels in rats fed carbohydrate-rich chow for 3 h post-exercise. In another set of experiments, doubling the amount of exercise (from 1 to 2 h) or electrical stimulation in serum (from 5 to 10 tetani) did not further elevate insulin-stimulated GT. In contrast, the combination of prior exercise (2 h) and electrical stimulation (10 tetani) had an additive effect on the subsequent increase in insulin-stimulated GT, suggesting that exercise and electrical stimulation may amplify insulin sensitivity through distinct mechanisms. These results suggest that: 1) TBC1D1 phosphorylation, but not AS160 phosphorylation, may be important for insulin-independent increase in skeletal muscle GT immediately after in vivo exercise or in vitro contraction; and 2) AS160 phosphorylation, but not TBC1D1 phosphorylation, may be important for insulin-dependent increase in skeletal muscle GT several hours after in vivo exercise, but not after in vitro contraction. | en_US |
dc.format.extent | 4459580 bytes | |
dc.format.extent | 1373 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | en_US |
dc.subject | Insulin Sensitivity | en_US |
dc.subject | Glucose Uptake | en_US |
dc.subject | GLUT4 Translocation | en_US |
dc.subject | Glycogen | en_US |
dc.subject | AMPK | en_US |
dc.subject | CaMK | en_US |
dc.title | Effects of In Vivo Exercise and In Vitro Contractile Activity on the Regulation of AS160, TBC1D1 and Glucose Transport in Rat Skeletal Muscle. | 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 | Horowitz, Jeffrey F. | en_US |
dc.contributor.committeemember | Lin, Jiandie | en_US |
dc.subject.hlbsecondlevel | Kinesiology and Sports | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbsecondlevel | Physiology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/75927/1/kfunai_1.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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