1 Supplemental Figure Legend 2 3 Figure S1 (related to Figure 3). 4 Gallery display of rich islet sympathetic innervation in young obese db/db mice. Three 5 channels of fluorescence signals are presented in parallel to illustrate the islet microstructure, 6 vasculature, and innervation in an integrated fashion. White: TH+ sympathetic nerves and 7 endocrine cells. Red: blood vessels. Green/blue: nuclear signals and autofluorescence. 8 9 Supplemental Movie Legends 10 11 Movie S1 (related to Figures 1A-F). 12 Whole-islet histology. A hyperplastic db/db islet is presented in the first half of the movie. The 13 second half of the movie shows the 360° panoramic projection of the db/db islet sympathetic 14 innervation. White: TH+ sympathetic nerves and endocrine cells. Red: blood vessels. Green: 15 nuclear signals and autofluorescence of acini. Depth: 325 m. Specimen is immersed in the RI: 16 1.52 solution. 17 18 Movie S2 (related to Figures 1G-I). 19 Matching the transmitted light and fluorescence signals in islet characterization. This movie 20 presents the middle section of a hyperplastic ob/ob islet. Pancreatic specimen is immersed in the 21 RI: 1.46 solution to improve the contrast in transmitted light microscopy. The islet and the 22 surrounding pancreatic structures are recorded with matched transmitted light and fluorescence 23 signals to verify the immunohistochemistry. White: TH+ sympathetic nerves and endocrine cells. 24 Red: blood vessels. Green: nuclei. Depth: 100 m. 25 26 Movie S3 (related to Figures 2D-I). 27 Two examples of the peri- and intra-islet ducts in db/db pancreas. Both the large, 28 hyperplastic islet (>300 m; the first half of the movie) and the medium islet (~100 m; second 29 half) are identified with the ingrowth of ductal epithelium. Green: ductal marker CK19. Red: 30 blood vessels. Blue: nuclear signals and autofluorescence of acini. 31 32 Movie S4 (related to Figures 3A-C and G-J). 33 Peri-ductal sympathetic innervation of the islet-duct complex in obesity. Two db/db islets 34 related to Figures 3A-C and 3G-H were recorded in the first two-thirds of the movie. The last 2 35 third of the movie shows the sympathetic innervation of the control islet in the db/+ lean 36 littermate (Figures 3I-J). In the control (db/+ lean littermate), the nuclear signals on the left side 37 of islet indicate a nearby duct around the arteriole(s). Prominent peri-ductal sympathetic 38 innervation can be seen but the nerves are not directly associated with the islet. White: TH+ 39 sympathetic nerves and endocrine cells. Red: blood vessels. Cyan: nuclear signals and 40 autofluorescence of acini. 41 42 Movie S5 (related to Figures 3D-F). 43 The neuro-insular-ductal complex. This movie shows the in-depth recording and 360° 44 panoramic projection of the neuro-insular-ductal complex in the obese db/db pancreas. Abundant 45 TH+ sympathetic axons and varicosities are seen concentrating at the islet-duct boundary, 46 forming the unique complex. Blue: insulin. White: TH. Red: blood vessels. 47 48 Movie S6 (related to Figures 6M-O). 49 Pericyte remodeling in the ob/ob islet. First half: tile scanning and in-depth projection of the 50 large, hyperplastic islet presented in Figure 6M. Second half: 360° projection of the NG2 signals 51 to reveal the drastic difference between the pericytes in the islet and that of the acini. The former 52 becomes hypertrophic with circular expansion of the processes to enclose the microvessels; the 53 latter stays intact with their processes extending toward the longitudinal direction of the 54 capillary. Green: pericyte surface marker NG2. Red: blood vessels. Blue: nuclear signals and 55 autofluorescence of acini. 56 3