Extended Data Fig. 2: Treatment with AAV-Adipsin prevents beta cell failure without affecting body weight or insulin sensitivity.

(a) Cfd mRNA levels were quantified by qPCR in the indicated tissues from db/db mice transduced with AAV-Adipsin or AAV-GFP at 1 month post-transduction (iWAT: n = 3 db/db-Adipsin, n = 4 db/db-GFP. vWAT: n = 3 for both groups. Liver: n = 4 for both groups. Kidney: n = 6 db/db-Adipsin, n = 5 db/db GFP. Islets: n = 2 for both groups). (b) Mouse serum adipsin levels were measured by ELISA (n = 5 db/db-GFP, n = 5 db/db-Adipsin, n = 2 B6 WT, n = 3 Adipsin KO). (c) Body weights of db/db mice transduced with AAV-Adipsin versus AAV-GFP at the indicated time points (n = 8 mice per group at 1 month post transduction and n = 15-16 mice per group at 1.5-months post transduction). (d) Glucose infusion rate during hyperinsulinemic euglycemic clamp in db/db mice treated with adipsin versus controls (n = 5 db/db-Adipsin, n = 6 db/db-GFP). (e) Scatterplot of fasting glucose and beta cell mass in db/db mice transduced with AAV-Adipsin versus controls (n = 18-21 per group). (f) Scatterplot of fasting insulin and beta cell mass in db/db mice injected with AAV-Adipsin versus controls (n = 18-21 per group). (g) Representative IHC staining for insulin (brown) in pancreases of two control and two adipsin transduced db/db mice. Areas in the dashed boxes are amplified in the panels at the right of each image. IHC was repeated at least twice independently with similar results. Scale bars, 1 mm left panels, 100 µm amplified regions. Data are expressed as mean ± s.e.m.