help button home button Endocrine Society JCEM JCEM Call for Nominations for EIC
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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 Egan, J. M.
Right arrow Articles by Elahi, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Egan, J. M.
Right arrow Articles by Elahi, D.
The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 3 1282-1290
Copyright © 2002 by The Endocrine Society

Other Original Articles

The Insulinotropic Effect of Acute Exendin-4 Administered to Humans: Comparison of Nondiabetic State to Type 2 Diabetes

Josephine M. Egan, Astrid R. Clocquet and Dariush Elahi

Diabetes and Metabolism Section (J.M.E., D.E.), Laboratory of Clinical Investigation, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224; and Geriatric Research Laboratory (A.R.C., D.E.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Dariush Elahi, Ph.D., Massachusetts General Hospital, Geriatric Research Laboratory, GRBSB-015, 55 Fruit Street, Boston, Massachusetts 02114. E-mail: . elahi.dariush{at}mgh.harvard.edu

Abstract

Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol·kg-1·min-1) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects.




This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
L. F Van Gaal, S. W Gutkin, and M. A Nauck
Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control?
Eur. J. Endocrinol., June 1, 2008; 158(6): 773 - 784.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Azuma, Z. Radikova, J. Mancino, F. G. S. Toledo, E. Thomas, C. Kangani, C. Dalla Man, C. Cobelli, J. J. Holst, C. F. Deacon, et al.
Measurements of Islet Function and Glucose Metabolism with the Dipeptidyl Peptidase 4 Inhibitor Vildagliptin in Patients with Type 2 Diabetes
J. Clin. Endocrinol. Metab., February 1, 2008; 93(2): 459 - 464.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
D. Kim, L. MacConell, D. Zhuang, P. A. Kothare, M. Trautmann, M. Fineman, and K. Taylor
Effects of Once-Weekly Dosing of a Long-Acting Release Formulation of Exenatide on Glucose Control and Body Weight in Subjects With Type 2 Diabetes
Diabetes Care, June 1, 2007; 30(6): 1487 - 1493.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
B. Zinman, B. J. Hoogwerf, S. Duran Garcia, D. R. Milton, J. M. Giaconia, D. D. Kim, M. E. Trautmann, and R. G. Brodows
The Effect of Adding Exenatide to a Thiazolidinedione in Suboptimally Controlled Type 2 Diabetes: A Randomized Trial
Ann Intern Med, April 3, 2007; 146(7): 477 - 485.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 The Diabetes EducatorHome page
P. S. Odegard, S. M. Setter, and J. L. Iltz
Update in the pharmacologic treatment of diabetes mellitus: focus on pramlintide and exenatide.
The Diabetes Educator, September 1, 2006; 32(5): 693 - 712.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Fehse, M. Trautmann, J. J. Holst, A. E. Halseth, N. Nanayakkara, L. L. Nielsen, M. S. Fineman, D. D. Kim, and M. A. Nauck
Exenatide Augments First- and Second-Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes
J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5991 - 5997.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
D. M. Kendall, M. C. Riddle, J. Rosenstock, D. Zhuang, D. D. Kim, M. S. Fineman, and A. D. Baron
Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Patients With Type 2 Diabetes Treated With Metformin and a Sulfonylurea
Diabetes Care, May 1, 2005; 28(5): 1083 - 1091.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
R. A. DeFronzo, R. E. Ratner, J. Han, D. D. Kim, M. S. Fineman, and A. D. Baron
Effects of Exenatide (Exendin-4) on Glycemic Control and Weight Over 30 Weeks in Metformin-Treated Patients With Type 2 Diabetes
Diabetes Care, May 1, 2005; 28(5): 1092 - 1100.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
E. Blase, K. Taylor, H.-y. Gao, M. Wintle, and M. Fineman
Pharmacokinetics of an Oral Drug (Acetaminophen) Administered at Various Times in Relation to Subcutaneous Injection of Exenatide (Exendin-4) in Healthy Subjects
J. Clin. Pharmacol., May 1, 2005; 45(5): 570 - 577.
[Abstract] [Full Text] [PDF]

Home page
 Clin. DiabetesHome page
K. Dungan and J. B. Buse
Glucagon-Like Peptide 1-Based Therapies for Type 2 Diabetes: A Focus on Exenatide
Clin. Diabetes, April 1, 2005; 23(2): 56 - 62.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. R. Gedulin, S. E. Nikoulina, P. A. Smith, G. Gedulin, L. L. Nielsen, A. D. Baron, D. G. Parkes, and A. A. Young
Exenatide (Exendin-4) Improves Insulin Sensitivity and {beta}-Cell Mass in Insulin-Resistant Obese fa/fa Zucker Rats Independent of Glycemia and Body Weight
Endocrinology, April 1, 2005; 146(4): 2069 - 2076.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
O. G. Kolterman, D. D. Kim, L. Shen, J. A. Ruggles, L. L. Nielsen, M. S. Fineman, and A. D. Baron
Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus
Am. J. Health Syst. Pharm., January 15, 2005; 62(2): 173 - 181.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
S. V Joy, P. T Rodgers, and A. C Scates
Incretin Mimetics as Emerging Treatments for Type 2 Diabetes
Ann. Pharmacother., January 1, 2005; 39(1): 110 - 118.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. E. Mager, D. R. Abernethy, J. M. Egan, and D. Elahi
Exendin-4 Pharmacodynamics: Insights from the Hyperglycemic Clamp Technique
J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 830 - 835.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
J. B. Buse, R. R. Henry, J. Han, D. D. Kim, M. S. Fineman, A. D. Baron, and for the Exenatide-113 Clinical Study Group
Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Sulfonylurea-Treated Patients With Type 2 Diabetes
Diabetes Care, November 1, 2004; 27(11): 2628 - 2635.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
L. A. Nikolaidis, D. Elahi, T. Hentosz, A. Doverspike, R. Huerbin, L. Zourelias, C. Stolarski, Y.-t. Shen, and R. P. Shannon
Recombinant Glucagon-Like Peptide-1 Increases Myocardial Glucose Uptake and Improves Left Ventricular Performance in Conscious Dogs With Pacing-Induced Dilated Cardiomyopathy
Circulation, August 24, 2004; 110(8): 955 - 961.
[Abstract] [Full Text] [PDF]

Home page
 JRSMHome page
C M. B Edwards
GLP-1: target for a new class of antidiabetic agents?
J R Soc Med, June 1, 2004; 97(6): 270 - 274.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
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]

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
 Diabetes CareHome page
M. S. Fineman, T. A. Bicsak, L. Z. Shen, K. Taylor, E. Gaines, A. Varns, D. Kim, and A. D. Baron
Effect on Glycemic Control of Exenatide (Synthetic Exendin-4) Additive to Existing Metformin and/or Sulfonylurea Treatment in Patients With Type 2 Diabetes
Diabetes Care, August 1, 2003; 26(8): 2370 - 2377.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
O. G. Kolterman, J. B. Buse, M. S. Fineman, E. Gaines, S. Heintz, T. A. Bicsak, K. Taylor, D. Kim, M. Aisporna, Y. Wang, et al.
Synthetic Exendin-4 (Exenatide) Significantly Reduces Postprandial and Fasting Plasma Glucose in Subjects with Type 2 Diabetes
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3082 - 3089.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. M. Egan, G. S. Meneilly, and D. Elahi
Effects of 1-mo bolus subcutaneous administration of exendin-4 in type 2 diabetes
Am J Physiol Endocrinol Metab, June 1, 2003; 284(6): E1072 - E1079.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
F. M. Gribble, L. Williams, A. K. Simpson, and F. Reimann
A Novel Glucose-Sensing Mechanism Contributing to Glucagon-Like Peptide-1 Secretion From the GLUTag Cell Line
Diabetes, May 1, 2003; 52(5): 1147 - 1154.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 Pharmacol. Rev.Home page
M. E. Doyle and J. M. Egan
Pharmacological Agents That Directly Modulate Insulin Secretion
Pharmacol. Rev., March 1, 2003; 55(1): 105 - 131.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
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]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Perry, N. J. Haughey, M. P. Mattson, J. M. Egan, and N. H. Greig
Protection and Reversal of Excitotoxic Neuronal Damage by Glucagon-Like Peptide-1 and Exendin-4
J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 881 - 888.
[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 © 2002 by The Endocrine Society