Abstract
Recent developments indicate that the regeneration of beta cell function and mass in patients with diabetes is possible. A regenerative approach may represent an alternative treatment option relative to current diabetes therapies that fail to provide optimal glycemic control. Here we report that the inactivation of GSK3 by small molecule inhibitors or RNA interference stimulates replication of INS-1E rat insulinoma cells. Specific and potent GSK3 inhibitors also alleviate the toxic effects of high concentrations of glucose and the saturated fatty acid palmitate on INS-1E cells. Furthermore, treatment of isolated rat islets with structurally diverse small molecule GSK3 inhibitors increases the rate beta cell replication by 2-3-fold relative to controls. We propose that GSK3 is a regulator of beta cell replication and survival. Moreover, our results suggest that specific inhibitors of GSK3 may have practical applications in beta cell regenerative therapies.
Highlights
In the course of the study, we investigated the effects of other known small molecule GSK3 inhibitors on beta cell function (Table 1)
The concentrations at which certain GSK3 inhibitors were toxic to INS-1E cell are indicated
The treatment periods are given in hours or days
Summary
In the course of the study, we investigated the effects of other known small molecule GSK3 inhibitors on beta cell function (Table 1). Both agents were toxic for INS-1E cells (Table 1) at concentration levels at which these agents have been reported to be tolerated or effective in other cell types (40, 54 –56). Summary of effects of small molecule GSK3 inhibitors on INS-1E cell functions
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