|
 |
|
|||||||
|
|||||||||
© 2001 by the American Diabetes Association, Inc.
Defective Glucose-Dependent Insulinotropic Polypeptide Receptor Expression in Diabetic Fatty Zucker Rats
1 Department of Physiology, University of British Columbia, Vancouver
2 Departments of Medicine and Physiology, University of Alberta, Edmonton, Canada
Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released postprandially from the small intestine and acts in concert with glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion from the pancreatic ß-cell. In type 2 diabetes, there is a decreased responsiveness of the pancreas to GIP; however, the insulin response to GLP-1 remains intact. The literature suggests that the ineffectiveness of GIP in type 2 diabetes may be a result of chronic homologous desensitization of the GIP receptor. Yet, there has been no conclusive evidence suggesting that GIP levels are elevated in diabetes. The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet. This hypothesis was tested using a strain of diabetic fatty Zucker rats. The obese rats displayed basal GIP levels similar to the control animals; however, they were unresponsive to a GIP infusion (4 pmol · min–1 · kg–1), whereas the lean animals displayed a significant reduction in blood glucose (GIP levels, 50% control after 60 min, P < 0.05) as well as a significant increase in circulating insulin. GIP also potently stimulated first-phase insulin secretion from isolated perifused islets (10.3 ± 3.0 x basal), and GIP and GLP-1 potentiated insulin secretion from the perfused pancreas (6 x control area under the curve [AUC]) from lean animals. GIP yielded no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion from the perfused VDF pancreas. Islets from lean animals subjected to static incubations with GIP showed a 2.2-fold increase in cAMP, whereas GIP failed to increase islet cAMP in the VDF islets. Finally, the expression of both GIP receptor mRNA and protein was decreased in islets from VDF rats. These data suggest that the decreased effectiveness of GIP in the VDF rat and in type 2 diabetes may be a result of a decreased receptor expression in the islet.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Zhou, M. F. A. Livak, M. Bernier, D. C. Muller, O. D. Carlson, D. Elahi, S. Maudsley, and J. M. Egan Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E538 - E547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. P. M. O'Harte, K. Hunter, V. A. Gault, N. Irwin, B. D. Green, B. Greer, P. Harriott, C. J. Bailey, and P. R. Flatt Antagonistic effects of two novel GIP analogs, (Hyp3)GIP and (Hyp3)GIPLys16PAL, on the biological actions of GIP and longer-term effects in diabetic ob/ob mice Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1674 - E1682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Wajchenberg {beta}-Cell Failure in Diabetes and Preservation by Clinical Treatment Endocr. Rev., April 1, 2007; 28(2): 187 - 218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Boylan, L. I. Jepeal, and M. M. Wolfe Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1287 - E1295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 J. Nyberg, M. F. Anderson, B. Meister, A.-M. Alborn, A.-K. Strom, A. Brederlau, A.-C. Illerskog, O. Nilsson, T. J. Kieffer, M. A. Hietala, et al. Glucose-Dependent Insulinotropic Polypeptide Is Expressed in Adult Hippocampus and Induces Progenitor Cell Proliferation J. Neurosci., February 16, 2005; 25(7): 1816 - 1825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Nauck, B. Baller, and J. J. Meier Gastric Inhibitory Polypeptide and Glucagon-Like Peptide-1 in the Pathogenesis of Type 2 Diabetes Diabetes, December 1, 2004; 53(suppl_3): S190 - S196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Meier, B. Gallwitz, B. Kask, C. F. Deacon, J. J. Holst, W. E. Schmidt, and M. A. Nauck Stimulation of Insulin Secretion by Intravenous Bolus Injection and Continuous Infusion of Gastric Inhibitory Polypeptide in Patients With Type 2 Diabetes and Healthy Control Subjects Diabetes, December 1, 2004; 53(suppl_3): S220 - S224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Holst and J. Gromada Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans Am J Physiol Endocrinol Metab, August 1, 2004; 287(2): E199 - E206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hinke, S. Manhart, K. Kuhn-Wache, C. Nian, H.-U. Demuth, R. A. Pederson, and C. H. S. McIntosh [Ser2]- and [Ser(P)2]Incretin Analogs: COMPARISON OF DIPEPTIDYL PEPTIDASE IV RESISTANCE AND BIOLOGICAL ACTIVITIES IN VITRO AND IN VIVO J. Biol. Chem., February 6, 2004; 279(6): 3998 - 4006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J.-G. Kim, L. L. Baggio, D. P. Bridon, J.-P. Castaigne, M. F. Robitaille, L. Jette, C. Benquet, and D. J. Drucker Development and Characterization of a Glucagon-Like Peptide 1-Albumin Conjugate: The Ability to Activate the Glucagon-Like Peptide 1 Receptor In Vivo Diabetes, March 1, 2003; 52(3): 751 - 759. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. E. Mayo, L. J. Miller, D. Bataille, S. Dalle, B. Goke, B. Thorens, and D. J. Drucker International Union of Pharmacology. XXXV. The Glucagon Receptor Family Pharmacol. Rev., March 1, 2003; 55(1): 167 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.A. Pospisilik, S.G. Stafford, H-U. Demuth, R. Brownsey, W. Parkhouse, D.T. Finegood, C.H.S. McIntosh, and R.A. Pederson Long-Term Treatment With the Dipeptidyl Peptidase IV Inhibitor P32/98 Causes Sustained Improvements in Glucose Tolerance, Insulin Sensitivity, Hyperinsulinemia, and {beta}-Cell Glucose Responsiveness in VDF (fa/fa) Zucker Rats Diabetes, April 1, 2002; 51(4): 943 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hinke, R. W. Gelling, R. A. Pederson, S. Manhart, C. Nian, H.-U. Demuth, and C. H.S. McIntosh Dipeptidyl Peptidase IV-Resistant [D-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats Diabetes, March 1, 2002; 51(3): 652 - 661. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Meier, K. Hucking, J. J. Holst, C. F. Deacon, W. H. Schmiegel, and M. A. Nauck Reduced Insulinotropic Effect of Gastric Inhibitory Polypeptide in First-Degree Relatives of Patients With Type 2 Diabetes Diabetes, November 1, 2001; 50(11): 2497 - 2504. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |