In Vivo Chemical Screen for Modifiers of Glucose Levels Identifies Alexidine as a Glucose-Lowering Agent

(A) Measurement of glucose levels in larval zebrafish after treatment with known hyper- and hypoglycemic agents (n = 3).

(B) S-score (log ratio of the fold change in glucose levels) ranking of the glucose-lowering ability of compounds in the Prestwick library. Alexidine’s score is depicted in red, and its chemical structure is shown on the graph.

(C) Alexidine dose-response curve (n = 5).

(D–G) Bright-field (D and E) and fluorescent (F and G) images of wild-type livers (D and F) and ablated livers (E and G).

(H) Glucose measurements in larvae with wild-type livers versus ablated livers.

(I) Glucose measurements in alexidine-treated larvae with ablated livers (n = 3).

(J–M) Bright-field (J and K) and fluorescent (L and M) images of wild-type (J and L) β cells and ablated β cells (K and M).

(N) Glucose measurements in larvae with wild-type β cells versus ablated β cells.

(O) Glucose measurements in alexidine-treated larvae with ablated β cells (n = 3).

Data are presented as mean ± SEM. p < 0.01. See also Figure S1.

Zebrafish Developmental Morphology and Mitochondrial Membrane Potential Remain Intact After Alexidine Treatment. Related to Figure 1.

Morpholino Oligonucleotide Knockdown of ptpmt1 and Generation of ptpmt1 Knockout Zebrafish. Related to Figure 2.