|
 |
|
|||||||
|
|||||||||
© 2002 by the American Diabetes Association, Inc.
Chronic Inhibition of Circulating Dipeptidyl Peptidase IV by FE 999011 Delays the Occurrence of Diabetes in Male Zucker Diabetic Fatty Rats
1 Ferring Research Institute and Division of Biology of Growth and Reproduction, Department of Pediatrics, University of Geneva School of Medicine, Geneva, Switzerland
2 Ferring Research, Southampton, U.K.
Acute suppression of dipeptidyl peptidase IV (DPP-IV) activity improves glucose tolerance in the Zucker fatty rat, a rodent model of impaired glucose tolerance, through stabilization of glucagon-like peptide (GLP)-1. This study describes the effects of a new and potent DPP-IV inhibitor, FE 999011, which is able to suppress plasma DPP-IV activity for 12 h after a single oral administration. In the Zucker fatty rat, FE 999011 dose-dependently attenuated glucose excursion during an oral glucose tolerance test and increased GLP-1 (7-36) release in response to intraduodenal glucose. Chronic treatment with FE 999011 (10 mg/kg, twice a day for 7 days) improved glucose tolerance, as suggested by a decrease in the insulin-to-glucose ratio. In the Zucker diabetic fatty (ZDF) rat, a rodent model of type 2 diabetes, chronic treatment with FE 999011 (10 mg/kg per os, once or twice a day) postponed the development of diabetes, with the twice-a-day treatment delaying the onset of hyperglycemia by 21 days. In addition, treatment with FE 999011 stabilized food and water intake to prediabetic levels and reduced hypertriglyceridemia while preventing the rise in circulating free fatty acids. At the end of treatment, basal plasma GLP-1 levels were increased, and pancreatic gene expression for GLP-1 receptor was significantly upregulated. This study demonstrates that DPP-IV inhibitors such as FE 999011 could be of clinical value to delay the progression from impaired glucose tolerance to type 2 diabetes.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Chahal and T.A. Chowdhury Gliptins: a new class of oral hypoglycaemic agent QJM, November 1, 2007; 100(11): 671 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Drucker Dipeptidyl Peptidase-4 Inhibition and the Treatment of Type 2 Diabetes: Preclinical biology and mechanisms of action Diabetes Care, June 1, 2007; 30(6): 1335 - 1343. [Full Text] [PDF]
|
|
|
|
 |
|
 B. E. Dunning and J. E. Gerich The Role of {alpha}-Cell Dysregulation in Fasting and Postprandial Hyperglycemia in Type 2 Diabetes and Therapeutic Implications Endocr. Rev., May 1, 2007; 28(3): 253 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. McKennon and R. K. Campbell The Physiology of Incretin Hormones and the Basis for DPP-4 Inhibitors The Diabetes Educator, January 1, 2007; 33(1): 55 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R K. Campbell Rationale for Dipeptidyl Peptidase 4 Inhibitors: A New Class of Oral Agents for the Treatment of Type 2 Diabetes Mellitus Ann. Pharmacother., January 1, 2007; 41(1): 51 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. F. Deacon, A. Plamboeck, M. M. Rosenkilde, J. de Heer, and J. J. Holst GIP-(3-42) does not antagonize insulinotropic effects of GIP at physiological concentrations Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E468 - E475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mu, J. Woods, Y.-P. Zhou, R. S. Roy, Z. Li, E. Zycband, Y. Feng, L. Zhu, C. Li, A. D. Howard, et al. Chronic Inhibition of Dipeptidyl Peptidase-4 With a Sitagliptin Analog Preserves Pancreatic {beta}-Cell Mass and Function in a Rodent Model of Type 2 Diabetes Diabetes, June 1, 2006; 55(6): 1695 - 1704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Riddle and D. J. Drucker Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1 Diabetes Care, February 1, 2006; 29(2): 435 - 449. [Full Text] [PDF]
|
|
|
|
 |
|
 B. F. Burkey, X. Li, L. Bolognese, B. Balkan, M. Mone, M. Russell, T. E. Hughes, and P. R. Wang Acute and Chronic Effects of the Incretin Enhancer Vildagliptin in Insulin-Resistant Rats J. Pharmacol. Exp. Ther., November 1, 2005; 315(2): 688 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xu, B. Zhu, Y. Teffera, D. E. Pan, C. G. Caldwell, G. Doss, R. A. Stearns, D. C. Evans, and M. G. Beconi METABOLIC ACTIVATION OF FLUOROPYRROLIDINE DIPEPTIDYL PEPTIDASE-IV INHIBITORS BY RAT LIVER MICROSOMES Drug Metab. Dispos., January 1, 2005; 33(1): 121 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Chien, L.-H. Huang, C.-Y. Chou, Y.-S. Chen, Y.-S. Han, G.-G. Chang, P.-H. Liang, and X. Chen One Site Mutation Disrupts Dimer Formation in Human DPP-IV Proteins J. Biol. Chem., December 10, 2004; 279(50): 52338 - 52345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Holst and C. Orskov The Incretin Approach for Diabetes Treatment: Modulation of Islet Hormone Release by GLP-1 Agonism Diabetes, December 1, 2004; 53(suppl_3): S197 - S204. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. F. Deacon Therapeutic Strategies Based on Glucagon-Like Peptide 1 Diabetes, September 1, 2004; 53(9): 2181 - 2189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Yasuda, T. Inoue, T. Nagakura, K. Yamazaki, K. Kira, T. Saeki, and I. Tanaka Metformin Causes Reduction of Food Intake and Body Weight Gain and Improvement of Glucose Intolerance in Combination with Dipeptidyl Peptidase IV Inhibitor in Zucker fa/fa Rats J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 614 - 619. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
L. Zhu, C. Tamvakopoulos, D. Xie, J. Dragovic, X. Shen, J. E. Fenyk-Melody, K. Schmidt, A. Bagchi, P. R. Griffin, N. A. Thornberry, et al. The Role of Dipeptidyl Peptidase IV in the Cleavage of Glucagon Family Peptides: IN VIVO METABOLISM OF PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE-(1-38) J. Biol. Chem., June 13, 2003; 278(25): 22418 - 22423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Pospisilik, J. Martin, T. Doty, J. A. Ehses, N. Pamir, F. C. Lynn, S. Piteau, H.-U. Demuth, C. H.S. McIntosh, and R. A. Pederson Dipeptidyl Peptidase IV Inhibitor Treatment Stimulates {beta}-Cell Survival and Islet Neogenesis in Streptozotocin-Induced Diabetic Rats Diabetes, March 1, 2003; 52(3): 741 - 750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. MacDonald, W. El-kholy, M. J. Riedel, A. M. F. Salapatek, P. E. Light, and M. B. Wheeler The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion Diabetes, December 1, 2002; 51(90003): S434 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Pospisilik, S. G. Stafford, H.-U. Demuth, C. H.S. McIntosh, and R. A. Pederson Long-Term Treatment With Dipeptidyl Peptidase IV Inhibitor Improves Hepatic and Peripheral Insulin Sensitivity in the VDF Zucker Rat: A Euglycemic-Hyperinsulinemic Clamp Study Diabetes, September 1, 2002; 51(9): 2677 - 2683. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |