The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice.

Research output: Contribution to journalJournal articleResearchpeer-review

Bidda Rolin, Marianne O Larsen, Carsten F Gotfredsen, Carolyn F Deacon, Richard D Carr, Michael Wilken, Lotte Bjerre Knudsen

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 beta-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. beta-Cell proliferation rate and mass were significantly increased with NN2211, but with exendin-4, only the beta-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 beta-cell mass and proliferation in db/db mice. NN2211 is currently in phase 2 clinical development.
Original languageEnglish
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume283
Issue number4
Pages (from-to)E745-52
ISSN0193-1849
DOIs
Publication statusPublished - 2002

Bibliographical note

Keywords: Animals; Blood Glucose; Body Weight; Cell Division; Diabetes Mellitus, Type 2; Eating; Female; Glucagon; Glucagon-Like Peptide 1; Hyperglycemia; Insulin; Islets of Langerhans; Mice; Mice, Inbred C57BL; Mice, Obese; Peptide Fragments; Peptides; Protein Precursors; Venoms

ID: 8417539