help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Baggio, L.
Right arrow Articles by Drucker, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Baggio, L.
Right arrow Articles by Drucker, D. J.
Endocrinology Vol. 141, No. 10 3703-3709
Copyright © 2000 by The Endocrine Society

ARTICLES

Glucagon-Like Peptide-1, But Not Glucose-Dependent Insulinotropic Peptide, Regulates Fasting Glycemia and Nonenteral Glucose Clearance in Mice1

Laurie Baggio2, Timothy J. Kieffer3 and Daniel J. Drucker4

Departments of Laboratory Medicine and Pathobiology and Medicine (L.B., D.J.D.), Banting and Best Diabetes Centre, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada M56 2C4; and the Departments of Medicine and Physiology (T.J.K.), University of Alberta, Alberta, Canada T6G 2S2

Address all correspondence and requests for reprints to: Dr. Daniel J. Drucker, Toronto General Hospital, 101 College Street CCRW3–845, Toronto, Ontario Canada M5G 2C4. E-mail: d.drucker{at}utoronto.ca

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) potentiate glucose-stimulated insulin secretion after enteral nutrient ingestion. We compared the relative incretin and nonincretin actions of GLP-1 and GIP in +/+ and GLP-1R-/- mice using exendin(9–39) and immunopurified anti-GIP receptor antisera (GIPR Ab) to antagonize GLP-1 and GIP action, respectively. Both antagonists produced a significant increase in glycemic excursion after oral glucose loading of +/+ mice (P < 0.05 for antagonists vs. controls). Exendin(9–39) also increased blood glucose and decreased glucose-stimulated insulin in +/+ mice after ip glucose loading [0.58 ± 0.02 vs. 0.47 ± 0.02 ng/ml in saline- vs. exendin(9–39)-treated mice, respectively, P < 0.05]. In contrast, GIPR Ab had no effect on glucose excursion or insulin secretion, after ip glucose challenge, in +/+ or GLP-1R-/- mice. Repeated administration of exendin(9–39) significantly increased blood glucose and reduced circulating insulin levels but had no effect on levels of pancreatic insulin or insulin messenger RNA transcripts. In contrast, no changes in plasma glucose, circulating insulin, pancreatic insulin content, or insulin messenger RNA were observed in mice, 18 h after administration of GIPR Ab. These findings demonstrate that GLP-1, but not GIP, plays an essential role in regulating glycemia, independent of enteral nutrient ingestion in mice in vivo.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
J. Ding, Y. Gao, J. Zhao, H. Yan, S.-y. Guo, Q.-x. Zhang, L.-s. Li, and X. Gao
Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice
Endocrinology, May 1, 2009; 150(5): 2136 - 2144.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. E. Ayala, D. P. Bracy, F. D. James, B. M. Julien, D. H. Wasserman, and D. J. Drucker
The Glucagon-Like Peptide-1 Receptor Regulates Endogenous Glucose Production and Muscle Glucose Uptake Independent of Its Incretin Action
Endocrinology, March 1, 2009; 150(3): 1155 - 1164.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. Duez, A. C. Smith, C. Xiao, A. Giacca, L. Szeto, D. J. Drucker, and G. F. Lewis
Acute Dipeptidyl Peptidase-4 Inhibition Rapidly Enhances Insulin-Mediated Suppression of Endogenous Glucose Production in Mice
Endocrinology, January 1, 2009; 150(1): 56 - 62.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
W. Kim and J. M. Egan
The Role of Incretins in Glucose Homeostasis and Diabetes Treatment
Pharmacol. Rev., December 1, 2008; 60(4): 470 - 512.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
I. Hadjiyanni, L. L. Baggio, P. Poussier, and D. J. Drucker
Exendin-4 Modulates Diabetes Onset in Nonobese Diabetic Mice
Endocrinology, March 1, 2008; 149(3): 1338 - 1349.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
J. E. Ayala, D. P. Bracy, T. Hansotia, G. Flock, Y. Seino, D. H. Wasserman, and D. J. Drucker
Insulin Action in the Double Incretin Receptor Knockout Mouse
Diabetes, February 1, 2008; 57(2): 288 - 297.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. J. Holst
The Physiology of Glucagon-like Peptide 1
Physiol Rev, October 1, 2007; 87(4): 1409 - 1439.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
G. Xu, H. Kaneto, D. R. Laybutt, V. F. Duvivier-Kali, N. Trivedi, K. Suzuma, G. L. King, G. C. Weir, and S. Bonner-Weir
Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia: Possible Contribution to Impaired Incretin Effects in Diabetes
Diabetes, June 1, 2007; 56(6): 1551 - 1558.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
M. C. Riddle and D. J. Drucker
Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1
Diabetes Care, February 1, 2006; 29(2): 435 - 449.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
Y.-C. Lu, C. Sternini, E. Rozengurt, and E. Zhukova
Release of Transgenic Human Insulin from Gastric G Cells: A Novel Approach for the Amelioration of Diabetes
Endocrinology, June 1, 2005; 146(6): 2610 - 2619.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. Hansotia, L. L. Baggio, D. Delmeire, S. A. Hinke, Y. Yamada, K. Tsukiyama, Y. Seino, J. J. Holst, F. Schuit, and D.J. Drucker
Double Incretin Receptor Knockout (DIRKO) Mice Reveal an Essential Role for the Enteroinsular Axis in Transducing the Glucoregulatory Actions of DPP-IV Inhibitors
Diabetes, May 1, 2004; 53(5): 1326 - 1335.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
D. J. Drucker
Enhancing Incretin Action for the Treatment of Type 2 Diabetes
Diabetes Care, October 1, 2003; 26(10): 2929 - 2940.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
N. Pamir, F. C. Lynn, A. M. J. Buchan, J. Ehses, S. A. Hinke, J. A. Pospisilik, K. Miyawaki, Y. Yamada, Y. Seino, C. H. S. McIntosh, et al.
Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis
Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E931 - E939.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. W. Gelling, X. Q. Du, D. S. Dichmann, J. Romer, H. Huang, L. Cui, S. Obici, B. Tang, J. J. Holst, C. Fledelius, et al.
Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice
PNAS, February 4, 2003; 100(3): 1438 - 1443.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Li, T. Hansotia, B. Yusta, F. Ris, P. A. Halban, and D. J. Drucker
Glucagon-like Peptide-1 Receptor Signaling Modulates beta Cell Apoptosis
J. Biol. Chem., January 3, 2003; 278(1): 471 - 478.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. W. Van Citters, M. Kabir, S. P. Kim, S. D. Mittelman, M. K. Dea, P. L. Brubaker, and R. N. Bergman
Elevated Glucagon-Like Peptide-1-(7-36)-Amide, but Not Glucose, Associated with Hyperinsulinemic Compensation for Fat Feeding
J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 5191 - 5198.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Yamada, M. Komatsu, Y. Sato, K. Yamauchi, I. Kojima, T. Aizawa, and K. Hashizume
Time-Dependent Stimulation of Insulin Exocytosis by 3',5'-Cyclic Adenosine Monophosphate in the Rat Islet {beta}-Cell
Endocrinology, November 1, 2002; 143(11): 4203 - 4209.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. Prasadan, E. Daume, B. Preuett, T. Spilde, A. Bhatia, H. Kobayashi, M. Hembree, P. Manna, and G. K. Gittes
Glucagon Is Required for Early Insulin-Positive Differentiation in the Developing Mouse Pancreas
Diabetes, November 1, 2002; 51(11): 3229 - 3236.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
E. E. Daniel, M. Anvari, J. E. T. Fox-Threlkeld, and T. J. McDonald
Local, exendin-(939)-insensitive, site of action of GLP-1 in canine ileum
Am J Physiol Gastrointest Liver Physiol, September 1, 2002; 283(3): G595 - G602.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Nian, J. Gu, D. M. Irwin, and D. J. Drucker
Human glucagon gene promoter sequences regulating tissue-specific versus nutrient-regulated gene expression
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2002; 282(1): R173 - R183.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. J. Drucker
Minireview: The Glucagon-Like Peptides
Endocrinology, February 1, 2001; 142(2): 521 - 527.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2000 by The Endocrine Society