dc.creator | An, Zhibo | |
dc.date.accessioned | 2020-08-22T20:37:57Z | |
dc.date.available | 2011-07-28 | |
dc.date.issued | 2009-07-28 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-07282009-114851 | |
dc.identifier.uri | http://hdl.handle.net/1803/13676 | |
dc.description.abstract | This dissertation focused on effects of the biological mediators, nitric oxide (NO) and serotonin in the regulation of net hepatic glucose uptake (NHGU). This work demonstrated that NHGU was suppressed by an increase in hepatic NO or cGMP, resulting from intraportal infusion of an NO donor SIN-1 or a cGMP analog 8-Br-cGMP, respectively. Conversely, NHGU was enhanced by the decrease in hepatic cGMP resulting from the intraportal infusion of a soluble guanylate cyclase inhibitor ODQ. These data raise the possibility that under basal conditions, there is an inhibitory tone due to hepatic NO/cGMP that restrains NHGU, and that this inhibitory signal is removed in response to portal glucose delivery thereby enhancing NHGU. In addition, this work showed that NHGU was enhanced by the increase in hepatic serotonin which resulted from intraportal infusion of the selective serotonin reuptake inhibitor escitalopram. This raises the possibility that the serotonergic input to the liver could increase with portal glucose delivery thus explaining part of its ability to increase NHGU. Taken together, these data give rise to the possibility that portal glucose delivery results in removal of an inhibitory signal (NO) and the simultaneous augmentation of a stimulatory signal (serotonin), thereby augmenting glucose uptake by the liver.
The studies described in this dissertation have a number of important implications. First, the data provide insight into mechanisms which can regulate NHGU in vivo. Second, they suggest a possible mechanism by which the portal glucose signal may work. Third, they suggest targets for pharmaceutical consideration as a means of correcting postprandial hyperglycemia in individuals with diabetes. | |
dc.format.mimetype | application/pdf | |
dc.subject | Net Hepatic Glucose Uptake | |
dc.subject | Serotonin | |
dc.subject | Liver | |
dc.subject | Nitrix Oxide | |
dc.subject | Portal Glucose Signal | |
dc.subject | Glycemia | |
dc.title | The regulation of net hepatic glucose uptake by nitric oxide and serotonin in vivo | |
dc.type | dissertation | |
dc.contributor.committeeMember | Masakazu Shiota | |
dc.contributor.committeeMember | Alvin C. Powers | |
dc.contributor.committeeMember | Jackie D. Corbin | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Molecular Physiology and Biophysics | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2011-07-28 | |
local.embargo.lift | 2011-07-28 | |
dc.contributor.committeeChair | David H. Wasserman | |