Endocrinology, Vol 137, 2968-2978, Copyright © 1996 by Endocrine Society

ARTICLES

Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor

BP Bullock, RS Heller and JF Habener
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, Massachusetts 02114.

The incretin hormone glucagon-like peptide-1 (GLP-1) is an important regulator of postprandial insulin secretion. In addition to its insulinotropic actions on pancreatic beta-cells, GLP-1 enhances glucose disposal by insulin-independent mechanisms, suggesting that GLP-1 receptors are located on extrapancreatic tissues. In this study, we examined the tissue distribution of GLP-1 receptor (GLP-lR) messenger RNA (mRNA) in rat by RNAse protection, RT-PCR, and in situ hybridization. We identified GLP-1R mRNA in the lung, pancreatic islets, stomach, and kidney by the RNAse protection assay. RT-PCR analysis also detected GLP-1R mRNA in the hypothalamus and heart. In situ hybridization experiments identified receptor mRNA in the gastric pits of the stomach, large nucleated cells in the lung, crypts of the duodenum, and pancreatic islets. No localized specific grains were found in kidney, skeletal muscle, heart, liver, or adipocytes. These results indicate that sequences corresponding to the cloned rat islet GLP-1 receptor are expressed in the pancreatic islets, lung, hypothalamus, stomach, heart, and kidney but not in adipose, liver, and skeletal muscle. Further, the GLP-1 receptor expressed in the kidney and heart may be structural variants of the known receptor. Therefore, the observed extrapancreatic actions of GLP-1 may not be strictly confined to interactions with the defined GLP-1 receptor.

This article has been cited by other articles:

				M. R. Hayes, K. P. Skibicka, and H. J. Grill Caudal Brainstem Processing Is Sufficient for Behavioral, Sympathetic, and Parasympathetic Responses Driven by Peripheral and Hindbrain Glucagon-Like-Peptide-1 Receptor Stimulation Endocrinology, August 1, 2008; 149(8): 4059 - 4068. [Abstract] [Full Text] [PDF]

				K. Ban, M. H. Noyan-Ashraf, J. Hoefer, S.-S. Bolz, D. J. Drucker, and M. Husain Cardioprotective and Vasodilatory Actions of Glucagon-Like Peptide 1 Receptor Are Mediated Through Both Glucagon-Like Peptide 1 Receptor-Dependent and -Independent Pathways Circulation, May 6, 2008; 117(18): 2340 - 2350. [Abstract] [Full Text] [PDF]

				M. Salehi, B. A. Aulinger, and D. A. D'Alessio Targeting {beta}-Cell Mass in Type 2 Diabetes: Promise and Limitations of New Drugs Based on Incretins Endocr. Rev., May 1, 2008; 29(3): 367 - 379. [Abstract] [Full Text] [PDF]

				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]

				K. G. Kumar, L. O. Byerley, J. Volaufova, D. J. Drucker, G. A. Churchill, R. Li, B. York, A. Zuberi, and B. K. S. Richards Genetic variation in Glp1r expression influences the rate of gastric emptying in mice Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R362 - R371. [Abstract] [Full Text] [PDF]

				S. E. Inzucchi and D. K. McGuire New Drugs for the Treatment of Diabetes: Part II: Incretin-Based Therapy and Beyond Circulation, January 29, 2008; 117(4): 574 - 584. [Abstract] [Full Text] [PDF]

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

				M. Tang-Christensen and M. A. Cowley GLP-1 analogs: satiety without malaise? Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R981 - R982. [Full Text] [PDF]

				J. J. Meier, J. J. Holst, W. E. Schmidt, and M. A. Nauck Reduction of hepatic insulin clearance after oral glucose ingestion is not mediated by glucagon-like peptide 1 or gastric inhibitory polypeptide in humans Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E849 - E856. [Abstract] [Full Text] [PDF]

				A. V. Andreeva, M. A. Kutuzov, and T. A. Voyno-Yasenetskaya Regulation of surfactant secretion in alveolar type II cells Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L259 - L271. [Abstract] [Full Text] [PDF]

				L. Simonsen, S. Pilgaard, C. Orskov, M. M. Rosenkilde, B. Hartmann, J. J. Holst, and C. F. Deacon Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal mass in GK rats Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G288 - G295. [Abstract] [Full Text] [PDF]

				G. L. Sowden, D. J. Drucker, D. Weinshenker, and S. J. Swoap Oxyntomodulin increases intrinsic heart rate in mice independent of the glucagon-like peptide-1 receptor Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R962 - R970. [Abstract] [Full Text] [PDF]

				D. Perez-Tilve, L. Gonzalez-Matias, M. Alvarez-Crespo, R. Leiras, S. Tovar, C. Dieguez, and F. Mallo Exendin-4 Potently Decreases Ghrelin Levels in Fasting Rats Diabetes, January 1, 2007; 56(1): 143 - 151. [Abstract] [Full Text] [PDF]

				K. G. Kumar, A. C. Poole, B. York, J. Volaufova, A. Zuberi, and B. K. S. Richards Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r) Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R207 - R216. [Abstract] [Full Text] [PDF]

				T. Zhao, P. Parikh, S. Bhashyam, H. Bolukoglu, I. Poornima, Y.-T. Shen, and R. P. Shannon Direct Effects of Glucagon-Like Peptide-1 on Myocardial Contractility and Glucose Uptake in Normal and Postischemic Isolated Rat Hearts J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1106 - 1113. [Abstract] [Full Text] [PDF]

				L. A. Nikolaidis, D. Elahi, Y.-T. Shen, and R. P. Shannon Active metabolite of GLP-1 mediates myocardial glucose uptake and improves left ventricular performance in conscious dogs with dilated cardiomyopathy Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2401 - H2408. [Abstract] [Full Text] [PDF]

				S. Stanley, K. Wynne, B. McGowan, and S. Bloom Hormonal Regulation of Food Intake Physiol Rev, October 1, 2005; 85(4): 1131 - 1158. [Abstract] [Full Text] [PDF]

				V. Sancho, M. V Trigo, N. Gonzalez, I. Valverde, W. J Malaisse, and M. L Villanueva-Penacarrillo Effects of glucagon-like peptide-1 and exendins on kinase activity, glucose transport and lipid metabolism in adipocytes from normal and type-2 diabetic rats J. Mol. Endocrinol., August 1, 2005; 35(1): 27 - 38. [Abstract] [Full Text] [PDF]

				P. K. Chelikani, A. C. Haver, and R. D. Reidelberger Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1695 - R1706. [Abstract] [Full Text] [PDF]

				K. Wynne, S. Stanley, B. McGowan, and S. Bloom Appetite control J. Endocrinol., February 1, 2005; 184(2): 291 - 318. [Abstract] [Full Text] [PDF]

				J. A. Koehler, B. Yusta, and D. J. Drucker The HeLa Cell Glucagon-Like Peptide-2 Receptor Is Coupled to Regulation of Apoptosis and ERK1/2 Activation through Divergent Signaling Pathways Mol. Endocrinol., February 1, 2005; 19(2): 459 - 473. [Abstract] [Full Text] [PDF]

				T. Nystrom, M. K. Gutniak, Q. Zhang, F. Zhang, J. J. Holst, B. Ahren, and A. Sjoholm Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1209 - E1215. [Abstract] [Full Text] [PDF]

				J. F. List and J. F. Habener Glucagon-like peptide 1 agonists and the development and growth of pancreatic {beta}-cells Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E875 - E881. [Abstract] [Full Text] [PDF]

				D. A. D'Alessio and T. P. Vahl Glucagon-like peptide 1: evolution of an incretin into a treatment for diabetes Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E882 - E890. [Abstract] [Full Text] [PDF]

				R. L. Prigeon, S. Quddusi, B. Paty, and D. A. D'Alessio Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E701 - E707. [Abstract] [Full Text] [PDF]

				J. Zhou, D. S. Roane, X. Xi, I. Bogacka, B. Li, D. H. Ryan, and R. J. Martin Short-Term Food Restriction and Refeeding Alter Expression of Genes Likely Involved in Brain Glucosensing Experimental Biology and Medicine, September 1, 2003; 228(8): 943 - 950. [Abstract] [Full Text] [PDF]

				R. Gros, X. You, L. L. Baggio, M. G. Kabir, A. M. Sadi, I. N. Mungrue, T. G. Parker, Q. Huang, D. J. Drucker, and M. Husain Cardiac Function in Mice Lacking the Glucagon-Like Peptide-1 Receptor Endocrinology, June 1, 2003; 144(6): 2242 - 2252. [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]

				M. Nakazaki, A. Crane, M. Hu, V. Seghers, S. Ullrich, L. Aguilar-Bryan, and J. Bryan cAMP-Activated Protein Kinase-Independent Potentiation of Insulin Secretion by cAMP Is Impaired in SUR1 Null Islets Diabetes, December 1, 2002; 51(12): 3440 - 3449. [Abstract] [Full Text] [PDF]

				J. M. Egan, G. S. Meneilly, J. F. Habener, and D. Elahi Glucagon-Like Peptide-1 Augments Insulin-Mediated Glucose Uptake in the Obese State J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3768 - 3773. [Abstract] [Full Text] [PDF]

				T. Perry, D. K. Lahiri, D. Chen, J. Zhou, K. T. Y. Shaw, J. M. Egan, and N. H. Greig A Novel Neurotrophic Property of Glucagon-Like Peptide 1: A Promoter of Nerve Growth Factor-Mediated Differentiation in PC12 Cells J. Pharmacol. Exp. Ther., March 1, 2002; 300(3): 958 - 966. [Abstract] [Full Text] [PDF]

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

				S. Mojsov Glucagon-like Peptide-1 (GLP-1) and the Control of Glucose Metabolism in Mammals and Teleost Fish Integr. Comp. Biol., April 1, 2000; 40(2): 246 - 258. [Abstract] [Full Text] [PDF]

				R. J. Bollag, Q. Zhong, P. Phillips, L. Min, L. Zhong, R. Cameron, A. L. Mulloy, H. Rasmussen, F. Qin, K. H. Ding, et al. Osteoblast-Derived Cells Express Functional Glucose-Dependent Insulinotropic Peptide Receptors Endocrinology, March 1, 2000; 141(3): 1228 - 1235. [Abstract] [Full Text] [PDF]

				T. J. Kieffer and J. Francis Habener The Glucagon-Like Peptides Endocr. Rev., December 1, 1999; 20(6): 876 - 913. [Abstract] [Full Text]

				K. Meeran, D. O’Shea, C. M. B. Edwards, M. D. Turton, M. M. Heath, I. Gunn, S. Abusnana, M. Rossi, C. J. Small, A. P. Goldstone, et al. Repeated Intracerebroventricular Administration of Glucagon-Like Peptide-1-(7-36) Amide or Exendin-(9-39) Alters Body Weight in the Rat Endocrinology, January 1, 1999; 140(1): 244 - 250. [Abstract] [Full Text]

				E. Benito, E. Blazquez, and M. A. Bosch Glucagon-Like Peptide-1-(7-36)Amide Increases Pulmonary Surfactant Secretion through a Cyclic Adenosine 3',5'-Monophosphate-Dependent Protein Kinase Mechanism in Rat Type II Pneumocytes Endocrinology, May 1, 1998; 139(5): 2363 - 2368. [Abstract] [Full Text] [PDF]