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-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
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