| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-cell mass in diabetic mice
1 Novo Nordisk, DK-2880 Bagsvaerd; and 2 The Panum Institute, University of Copenhagen, DK-2200 Copenhagen, Denmark
NN2211 is a long-acting,
metabolically stable glucagon-like peptide-1 (GLP-1) derivative
designed for once daily administration in humans. NN2211 dose
dependently reduced the glycemic levels in ob/ob mice, with
antihyperglycemic activity still evident 24 h postdose. Apart from
an initial reduction in food intake, there were no significant
differences between NN2211 and vehicle treatment, and body weight was
not affected. Histological examination revealed that 
-cell
proliferation and mass were not increased significantly in
ob/ob mice with NN2211, although there was a strong tendency for increased proliferation. In db/db mice, exendin-4 and
NN2211 decreased blood glucose compared with vehicle, but NN2211 had a
longer duration of action. Food intake was lowered only on day 1 with both compounds, and body weight was unaffected. -Cell proliferation rate and mass were significantly increased with NN2211,
but with exendin-4, only the -cell proliferation rate was
significantly increased. In conclusion, NN2211 reduced blood glucose
after acute and chronic treatment in ob/ob and
db/db mice and was associated with increased -cell mass
and proliferation in db/db mice. NN2211 is currently in
phase 2 clinical development.
incretin hormones; diabetes; animal models; glucagon-like peptide-1
This article has been cited by other articles:
|
|
 |
|
  J. J Neumiller and R K. Campbell Liraglutide: A Once-Daily Incretin Mimetic for the Treatment of Type 2 Diabetes Mellitus Ann. Pharmacother., September 1, 2009; 43(9): 1433 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yan, W. Gu, J. Yang, V. Bi, Y. Shen, E. Lee, K. A. Winters, R. Komorowski, C. Zhang, J. J. Patel, et al. Fully Human Monoclonal Antibodies Antagonizing the Glucagon Receptor Improve Glucose Homeostasis in Mice and Monkeys J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 102 - 111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Nauck, A. Frid, K. Hermansen, N. S. Shah, T. Tankova, I. H. Mitha, M. Zdravkovic, M. During, D. R. Matthews, and for the LEAD-2 Study Group Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes: The LEAD (Liraglutide Effect and Action in Diabetes)-2 study Diabetes Care, January 1, 2009; 32(1): 84 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Nauck The modulating effects of GLP-1 in type 2 diabetes The British Journal of Diabetes & Vascular Disease, November 1, 2008; 8(2_suppl): S1 - S2. [PDF]
|
|
|
|
|
|
B. Gallwitz Managing the {beta}-cell with GLP-1 in type 2 diabetes The British Journal of Diabetes & Vascular Disease, November 1, 2008; 8(2_suppl): S19 - S25. [Abstract] [PDF]
|
|
|
|
|
|
M. A Nauck Liraglutide, a once-daily human GLP-1 analogue The British Journal of Diabetes & Vascular Disease, November 1, 2008; 8(2_suppl): S26 - S33. [Abstract] [PDF]
|
|
|
|
|
|
T. Vilsboll, M. Zdravkovic, T. Le-Thi, T. Krarup, O. Schmitz, J.-P. Courreges, R. Verhoeven, I. Buganova, and S. Madsbad Liraglutide, a Long-Acting Human Glucagon-Like Peptide-1 Analog, Given as Monotherapy Significantly Improves Glycemic Control and Lowers Body Weight Without Risk of Hypoglycemia in Patients With Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1608 - 1610. [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Park, H. W. Kim, S. H. Ko, J. H. Lim, G. R. Ryu, H. W. Chung, S. W. Han, S. J. Shin, B. K. Bang, M. D. Breyer, et al. Long-Term Treatment of Glucagon-Like Peptide-1 Analog Exendin-4 Ameliorates Diabetic Nephropathy through Improving Metabolic Anomalies in db/db Mice J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1227 - 1238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H Claus, C. Q Pan, J. M Buxton, L. Yang, J. C Reynolds, N. Barucci, M. Burns, A. A Ortiz, S. Roczniak, J. N Livingston, et al. Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes J. Endocrinol., February 1, 2007; 192(2): 371 - 380. [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]
|
|
|
|
 |
|
 K. Raun, P. von Voss, C. F. Gotfredsen, V. Golozoubova, B. Rolin, and L. B. Knudsen Liraglutide, a Long-Acting Glucagon-Like Peptide-1 Analog, Reduces Body Weight and Food Intake in Obese Candy-Fed Rats, Whereas a Dipeptidyl Peptidase-IV Inhibitor, Vildagliptin, Does Not Diabetes, January 1, 2007; 56(1): 8 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Bouwens and I. Rooman Regulation of Pancreatic Beta-Cell Mass Physiol Rev, October 1, 2005; 85(4): 1255 - 1270. [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]
|
|
|
|
|
|
L. L. Baggio, J.-G. Kim, and D. J. Drucker Chronic Exposure to GLP-1R Agonists Promotes Homologous GLP-1 Receptor Desensitization In Vitro but Does Not Attenuate GLP-1R-Dependent Glucose Homeostasis In Vivo Diabetes, December 1, 2004; 53(suppl_3): S205 - S214. [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. 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]
|
|
|
|
|
|
C. Thorkildsen, S. Neve, B. D. Larsen, E. Meier, and J. S. Petersen Glucagon-Like Peptide 1 Receptor Agonist ZP10A Increases Insulin mRNA Expression and Prevents Diabetic Progression in db/db Mice J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Brand, J. Sturis, C. F. Gotfredsen, J. Fleckner, C. Fledelius, B. F. Hansen, B. Andersen, J.-M. Ye, P. Sauerberg, and K. Wassermann Dual PPARalpha /gamma activation provides enhanced improvement of insulin sensitivity and glycemic control in ZDF rats Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E841 - E854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Stoffers, B. M. Desai, D. D. DeLeon, and R. A. Simmons Neonatal Exendin-4 Prevents the Development of Diabetes in the Intrauterine Growth Retarded Rat Diabetes, March 1, 2003; 52(3): 734 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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 | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
