dc.creator | Johnson, Kathryn Mercedes Stettler | |
dc.date.accessioned | 2020-08-22T00:29:32Z | |
dc.date.available | 2010-05-05 | |
dc.date.issued | 2008-05-05 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-04092008-163323 | |
dc.identifier.uri | http://hdl.handle.net/1803/12078 | |
dc.description.abstract | Glucagon-like peptide-one (GLP-1) secreted from the endocrine L cell in the gut after a meal results in elevations of the peptide in arterial blood, the hepatic portal vein (~2x arterial levels) and vasculature in the gut directly surrounding the site of secretion (~4x arterial levels). An intraportal physiological bolus of GLP-1 increases afferent vagal signaling from the hepatoportal region, which could initiate the gluco-regulatory effects of GLP-1.
In Specific Aim I, hyperglycemia was induced with a combination of peripheral and intraportal glucose infusions in the 42 h fasted conscious dog. GLP-1 was given intraportally or into the hepatic artery in physiologic amounts. Intraportal, but not hepatic artery, GLP-1 delivery significantly increased nonhepatic glucose uptake relative to that observed in saline infused control dogs, without altering pancreatic hormone levels.
In Specific Aim II, GLP-1 or saline was infused intraportally in 42 h fasted conscious dogs, and hyperglycemia was induced by peripheral glucose infusion, alone. Under these conditions, GLP-1 did not alter pancreatic hormone levels or glucose utilization.
In Specific Aim III, dogs were fasted for 18 h to increase ƒÒ-cell responsiveness and insulin sensitivity. GLP-1 or saline was infused intraportally, and hyperglycemia was induced by a combination of intraportal and peripheral glucose infusion. GLP-1 had no effect despite the presence of a portal vein glucose infusion.
In Specific Aim IV, dogs were administered a mixed meal in the presence or absence of exendin (9-39), a GLP-1R antagonist. Blocking postprandial GLP-1 action resulted in expedited gastric emptying for about 2 h which ultimately increased peripheral glycemia in both normal and insulin resistant dogs. Blocking postprandial GLP-1 action did not enhance the incretin effect in either group of animals.
In conclusion we found that in the dog 1) GLP-1R activation is not responsible for the incretin effect, 2) the dominant effect of postprandial GLP-1 secretion is slowed gastric emptying, 3) GLP-1 has a small direct effect on the liver, and 4) intraportally delivered GLP-1 induces increased nonhepatic glucose uptake under conditions that mimic a meal. | |
dc.format.mimetype | application/pdf | |
dc.subject | hepatic portal vein | |
dc.subject | Glucagon-like peptide-1 -- Physiological effect | |
dc.subject | Glucose -- Metabolism | |
dc.subject | GLP-1 | |
dc.title | The role of physiological elevations of glucagon-like peptide-one in glucose regulation in the dog in vivo | |
dc.type | dissertation | |
dc.contributor.committeeMember | Kevin Niswender | |
dc.contributor.committeeMember | Masakazu Shiota | |
dc.contributor.committeeMember | Alyssa Hasty | |
dc.contributor.committeeMember | Mary Moore | |
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 | 2010-05-05 | |
local.embargo.lift | 2010-05-05 | |
dc.contributor.committeeChair | David Wasserman | |