| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diabeteszentrum Bad Lauterberg (F.F., M.A.N.), D-37431 Bad Lauterberg im Harz, Germany; Eli Lilly & Co. (M.T.), Hamburg, Germany, and Indianapolis, Indiana 46285; Department of Medical Physiology (J.J.H.), Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark; and Amylin Pharmaceuticals (A.E.H., N.N., L.L.N., M.S.F., D.D.K.), San Diego, California 92121
Address all correspondence and requests for reprints to: Professor Dr. Med. Michael Nauck, Diabeteszentrum Bad Lauterberg, Kirchberg 21, D-37431 Bad Lauterberg im Harz, Germany. E-mail: m.nauck{at}diabeteszentrum.de.
Context: First-phase insulin secretion (within 10 min after a sudden rise in plasma glucose) is reduced in type 2 diabetes mellitus (DM2). The incretin mimetic exenatide has glucoregulatory activities in DM2, including glucose-dependent enhancement of insulin secretion.
Objective: The objective of the study was to determine whether exenatide can restore a more normal pattern of insulin secretion in subjects with DM2.
Design: Fasted subjects received iv insulin infusion to reach plasma glucose 4.4–5.6 mmol/liter. Subjects received iv exenatide (DM2) or saline (DM2 and healthy volunteers), followed by iv glucose challenge.
Patients: Thirteen evaluable DM2 subjects were included in the study: 11 males, two females; age, 56 ± 7 yr; body mass index, 31.7 ± 2.4 kg/m2; hemoglobin A1c, 6.6 ± 0.7% (mean ± SD) treated with diet/exercise (n = 1), metformin (n = 10), or acarbose (n = 2). Controls included 12 healthy, weight-matched subjects with normal glucose tolerance: nine males, three females; age, 57 ± 9 yr; and body mass index, 32.0 ± 3.0 kg/m2.
Setting: The study was conducted at an academic hospital.
Main Outcome Measures: Plasma insulin, plasma C-peptide, insulin secretion rate (derived by deconvolution), and plasma glucagon were the main outcome measures.
Results: DM2 subjects administered saline had diminished first-phase insulin secretion, compared with healthy control subjects. Exenatide-treated DM2 subjects had an insulin secretory pattern similar to healthy subjects in both first (0–10 min) and second (10–180 min) phases after glucose challenge, in contrast to saline-treated DM2 subjects. In exenatide-treated DM2 subjects, the most common adverse event was moderate nausea (two of 13 subjects).
Conclusions: Short-term exposure to exenatide can restore the insulin secretory pattern in response to acute rises in glucose concentrations in DM2 patients who, in the absence of exenatide, do not display a first phase of insulin secretion. Loss of first-phase insulin secretion in DM2 patients may be restored by treatment with exenatide.
This article has been cited by other articles:
 |
|
 |
|
  C. W. Chia and J. M. Egan Incretin-Based Therapies in Type 2 Diabetes Mellitus J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3703 - 3716. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Elkind-Hirsch, O. Marrioneaux, M. Bhushan, D. Vernor, and R. Bhushan Comparison of Single and Combined Treatment with Exenatide and Metformin on Menstrual Cyclicity in Overweight Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2670 - 2678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 L R Ranganath Incretins: pathophysiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 J. Clin. Pathol., April 1, 2008; 61(4): 401 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Davis, D. Johns, D. Maggs, H. Xu, J. H. Northrup, and R. G. Brodows Exploring the Substitution of Exenatide for Insulin in Patients With Type 2 Diabetes Treated With Insulin in Combination With Oral Antidiabetes Agents Diabetes Care, November 1, 2007; 30(11): 2767 - 2772. [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]
|
|
|
|
 |
|
 L. E. John, M. P. Kane, R. S. Busch, and R. A. Hamilton Expanded Use of Exenatide in the Management of Type 2 Diabetes Diabetes Spectr, January 1, 2007; 20(1): 59 - 63. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ogata, K. Tokuyama, S. Nagasaka, A. Ando, I. Kusaka, N. Sato, A. Goto, S. Ishibashi, K. Kiyono, Z. R. Struzik, et al. Long-range negative correlation of glucose dynamics in humans and its breakdown in diabetes mellitus Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1638 - R1643. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hinnen, L. L. Nielsen, A. Waninger, and P. Kushner Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes J Am Board Fam Med, November 1, 2006; 19(6): 612 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Gambert and S. Pinkstaff Emerging Epidemic: Diabetes in Older Adults: Demography, Economic Impact, and Pathophysiology Diabetes Spectr, October 1, 2006; 19(4): 221 - 228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Yoo, D. M. Triller, and D. J. Yoo Exenatide: A New Option for the Treatment of Type 2 Diabetes Ann. Pharmacother., October 1, 2006; 40(10): 1777 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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 | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
