HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/2/E269    most recent 90222.2008v2 90222.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Ionut, V. Articles by Bergman, R. N. Search for Related Content PubMed PubMed Citation Articles by Ionut, V. Articles by Bergman, R. N.

Exenatide can reduce glucose independent of islet hormones or gastric emptying

Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California

Submitted 11 February 2008 ; accepted in final form 14 May 2008

Exenatide is a long-acting glucagon-like peptide-1 (GLP-1) mimetic used in the treatment of type 2 diabetes. There is increasing evidence that GLP-1 can influence glycemia not only via pancreatic (insulinotropic and glucagon suppression) and gastric-emptying effects, but also via an independent mechanism mediated by portal vein receptors. The aim of our study was to investigate whether exenatide has an islet- and gastric-independent glycemia-reducing effect, similar to GLP-1. First, we administered mixed meals, with or without exenatide (20 µg sc) to dogs. Second, to determine whether exenatide-induced reduction in glycemia is independent of slower gastric emptying, in the same animals we infused glucose intraportally (to simulate meal test glucose appearance) with exenatide, exenatide + the intraportal GLP-1 receptor antagonist exendin-(9-39), or saline. Exenatide markedly decreased postprandial glucose: net 0- to 135-min area under the curve = +526 ± 315 and –536 ± 197 mg·dl^–1·min^–1 with saline and exenatide, respectively (P < 0.05). Importantly, the decrease in plasma glucose occurred without a corresponding increase in postprandial insulin but was accompanied by delayed gastric emptying and lower glucagon. Significantly lower glycemia was induced by intraportal glucose infusion with exenatide than with saline (92 ± 1 vs. 97 ± 1 mg/dl, P < 0.001) in the absence of hyperinsulinemia or glucagon suppression. The exenatide-induced lower glycemia was partly reversed by intraportal exendin-(9-39): 95 ± 3 and 92 ± 3 mg/dl with exenatide + antagonist and exenatide, respectively (P < 0.01). Our results suggest that, similar to GLP-1, exenatide lowers glycemia via a novel mechanism independent of islet hormones and slowing of gastric emptying. We hypothesize that receptors in the portal vein, via a neural mechanism, increase glucose clearance independent of islet hormones.

glucagon-like peptide-1; insulin-independent; glucose regulation

This article has been cited by other articles:

				R. A. DeFronzo From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus Diabetes, April 1, 2009; 58(4): 773 - 795. [Full Text] [PDF]

				Highlights From The Literature Physiology, February 1, 2009; 24(1): 4 - 7. [Full Text] [PDF]

				D. Zheng, V. Ionut, V. Mooradian, D. Stefanovski, and R. N. Bergman Exenatide Sensitizes Insulin-Mediated Whole-Body Glucose Disposal and Promotes Uptake of Exogenous Glucose by the Liver Diabetes, February 1, 2009; 58(2): 352 - 359. [Abstract] [Full Text] [PDF]

				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]