| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amylin Pharmaceuticals, Inc., San Diego, California 92121
Address all correspondence and requests for reprints to: Andrew A. Young, M.D., Ph.D., Amylin Pharmaceuticals, Inc., 9360 Towne Centre Drive, Suite 110, San Diego, California 92121. E-mail: ayoung{at}amylin.com.
The effects of the incretin mimetic exenatide (exendin-4) on metabolic parameters, insulin sensitivity, and ß-cell mass were examined in nondiabetic, insulin-resistant obese fa/fa Zucker rats. After 6 wk of treatment, ad libitum-fed exenatide-treated (EX) and pair-fed vehicle control (PF) rats had comparable food intake, body weight, hemoglobin A1c (HbA1c), and fasting plasma concentrations of glucose, insulin, and lipids. Concurrent decreases in food intake and weight gain were observed in EX and PF rats, compared with ad libitum-fed vehicle control (CON) rats (P < 0.001). The increases in HbA1c and fasting plasma insulin concentrations that occur during the normal progression of this disease model were significantly reduced in EX and PF rats, compared with CON rats (P < 0.001). The insulin sensitivity index (ISI; glucose infusion rate to plasma insulin concentration) measured during a hyperinsulinemic euglycemic clamp was 224% higher in EX rats than CON rats (P < 0.001) and 61% higher in EX rats than PF rats (P < 0.004). The latter difference was despite comparable HbA1c, fasting glucose, fasting insulin, total cholesterol, high-density lipoprotein, and daily food consumption between EX and PF animals. In the absence of exenatide, ß-cell mass was hyperbolically related to ISI (ß-cell mass * ISI was constant). Analogous to the disposition index, the ß-cell mass * ISI product was 63% greater in EX than PF rats (P < 0.05). Thus, exenatide increased ß-cell mass to a greater extent than would be expected in animals of comparable insulin resistance, suggesting a direct trophic effect on islet neogenesis in obese fa/fa rats independent of body weight and glycemia.
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
 |
|
 M. S. Winzell and B. Ahren Durable islet effects on insulin secretion and protein kinase A expression following exendin-4 treatment of high-fat diet-fed mice J. Mol. Endocrinol., February 1, 2008; 40(2): 93 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Goldfine, E. C. Mun, E. Devine, R. Bernier, M. Baz-Hecht, D. B. Jones, B. E. Schneider, J. J. Holst, and M. E. Patti Patients with Neuroglycopenia after Gastric Bypass Surgery Have Exaggerated Incretin and Insulin Secretory Responses to a Mixed Meal J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4678 - 4685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chen, S. Turner, E. Tsang, J. Stark, H. Turner, A. Mahsut, K. Keifer, M. Goldfinger, and M. K. Hellerstein Measurement of pancreatic islet cell proliferation by heavy water labeling Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1459 - E1464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Bray and F. L. Greenway Pharmacological Treatment of the Overweight Patient Pharmacol. Rev., June 1, 2007; 59(2): 151 - 184. [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Lee, S. Shin, T. Shigihara, E. Hahm, M.-J. Liu, J. Han, J.-W. Yoon, and H.-S. Jun Glucagon-Like Peptide-1 Gene Therapy in Obese Diabetic Mice Results in Long-Term Cure of Diabetes by Improving Insulin Sensitivity and Reducing Hepatic Gluconeogenesis Diabetes, June 1, 2007; 56(6): 1671 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsunekawa, N. Yamamoto, K. Tsukamoto, Y. Itoh, Y. Kaneko, T. Kimura, Y. Ariyoshi, Y. Miura, Y. Oiso, and I. Niki Protection of pancreatic {beta}-cells by exendin-4 may involve the reduction of endoplasmic reticulum stress; in vivo and in vitro studies J. Endocrinol., April 1, 2007; 193(1): 65 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chen, J. Liao, N. Li, C. Zhou, Q. Liu, G. Wang, R. Zhang, S. Zhang, L. Lin, K. Chen, et al. From the Cover: A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db/db mice PNAS, January 16, 2007; 104(3): 943 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Kang, M.-J. Kim, H.-I. Jang, K.-H. Koh, K.-S. Yum, D.-J. Rhie, S. H. Yoon, S. J. Hahn, M.-S. Kim, and Y.-H. Jo Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E215 - E222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. L. Williams, D. G. Baskin, and M. W. Schwartz Leptin Regulation of the Anorexic Response to Glucagon-Like Peptide-1 Receptor Stimulation Diabetes, December 1, 2006; 55(12): 3387 - 3393. [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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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 | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
