| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
HORMONES AND SIGNALING
1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee; 2Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Centre de Recherches en Nutrition Humaine de Clermont-Ferrand, Ceyrat, France; and 3Diabetes Research and Training Center, Vanderbilt University School of Medicine, Nashville, Tennessee
Submitted 21 March 2005 ; accepted in final form 26 July 2005
Whether glucagon-like peptide (GLP)-1 requires the hepatic portal vein to elicit its insulin secretion-independent effects on glucose disposal in vivo was assessed in conscious dogs using tracer and arteriovenous difference techniques. In study 1, six conscious overnight-fasted dogs underwent oral glucose tolerance testing (OGTT) to determine target GLP-1 concentrations during clamp studies. Peak arterial and portal values during OGTT ranged from 23 to 65 pM and from 46 to 113 pM, respectively. In study 2, we conducted hyperinsulinemic-hyperglycemic clamp experiments consisting of three periods (P1, P2, and P3) during which somatostatin, glucagon, insulin and glucose were infused. The control group received saline, the PePe group received GLP-1 (1 pmol·kg–1·min–1) peripherally, the PePo group received GLP-1 (1 pmol·kg–1·min–1) peripherally (P2) and then intraportally (P3), and the PeHa group received GLP-1 (1 pmol·kg–1·min–1) peripherally (P2) and then through the hepatic artery (P3) to increase the hepatic GLP-1 load to the same extent as in P3 in the PePo group (n = 8 dogs/group). Arterial GLP-1 levels increased similarly in all groups during P2 (
50 pM), whereas portal GLP-1 levels were significantly increased (2-fold) in the PePo vs. PePe and PeHa groups during P3. During P2, net hepatic glucose uptake (NHGU) increased slightly but not significantly (vs. P1) in all groups. During P3, GLP-1 increased NHGU in the PePo and PeHa groups more than in the control and PePe groups (change of 10.8 ± 1.3 and 10.6 ± 1.0 vs. 5.7 ± 1.0 and 5.4 ± 0.8 µmol·kg–1·min–1, respectively, P < 0.05). In conclusion, physiological GLP-1 levels increase glucose disposal in the liver, and this effect does not involve GLP-1 receptors located in the portal vein.
glucose uptake; dog; oral glucose tolerance test; glucagon-like peptide-1
This article has been cited by other articles:
|
|
 |
|
  D. S. Edgerton, K. M.S. Johnson, D. W. Neal, M. Scott, C. H. Hobbs, X. Zhang, A. Duttaroy, and A. D. Cherrington Inhibition of Dipeptidyl Peptidase-4 by Vildagliptin During Glucagon-Like Peptide 1 Infusion Increases Liver Glucose Uptake in the Conscious Dog Diabetes, January 1, 2009; 58(1): 243 - 249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. S. Johnson, D. S. Edgerton, T. Rodewald, M. Scott, B. Farmer, D. Neal, and A. D. Cherrington Intraportally delivered GLP-1, in the presence of hyperglycemia induced via peripheral glucose infusion, does not change whole body glucose utilization Am J Physiol Endocrinol Metab, February 1, 2008; 294(2): E380 - E384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. S. Johnson, D. S. Edgerton, T. Rodewald, M. Scott, B. Farmer, D. Neal, and A. D. Cherrington Intraportal GLP-1 infusion increases nonhepatic glucose utilization without changing pancreatic hormone levels Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1085 - E1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. D. Cani, C. Knauf, M. A. Iglesias, D. J. Drucker, N. M. Delzenne, and R. Burcelin Improvement of glucose tolerance and hepatic insulin sensitivity by oligofructose requires a functional glucagon-like Peptide 1 receptor. Diabetes, May 1, 2006; 55(5): 1484 - 1490. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
