Figure 2.

Distribution of liraglutide⁵⁹⁴ or exendin(9‐39)⁵⁹⁴ in the pancreas and brain. (a–l) Representative images of mouse islets stained with Hoechst nuclear stain (blue), insulin (green) and liraglutide⁵⁹⁴/exendin(9‐39)⁵⁹⁴ (red). (a, c, e, d) Insulin‐ and liraglutide⁵⁹⁴/exendin(9‐39)⁵⁹⁴‐positive cells. (b, d, f, h) The same images as in (a, c, e, d) with only Hoechst and liraglutide⁵⁹⁴/exendin(9‐39)⁵⁹⁴ signal. (a–d) In C57BL/6J mice, both liraglutide⁵⁹⁴ and exendin(9‐39)⁵⁹⁴ were detected in cells expressing insulin; (e–h) however, in mice lacking a functional glucagon‐like peptide‐1 receptor, no liraglutide⁵⁹⁴ or exendin(9‐39)⁵⁹⁴ signal could be detected in insulin expressing β‐cells. (i, j, n) High‐magnification images showed that liraglutide⁵⁹⁴ was internalized and the fluorescent signal was located in the cytoplasm, (k, l, p) while exendin(9‐39)⁵⁹⁴ remained at the plasma membrane. In the brain, (m, n) liraglutide⁵⁹⁴ had access to arcuate nucleus (ARC), in which it bound the glucagon‐like peptide‐1 receptor and internalized, (o, p) whereas exendin(9‐39)⁵⁹⁴ labeled the same population of cells, but without internalization. Scale bars, 100 μm (m, o), 50 μm (a–h), 10 μm (i–l, n, p). ©American Society for Clinical Investigation and reproduced from Secher et al.12 with permission.