Zinc-Chelating Small Molecules Preferentially Accumulate and Function within Pancreatic β Cells.

ABSTRACT: Diabetes is a hyperglycemic condition characterized by pancreatic β-cell dysfunction and depletion. Whereas methods for monitoring β-cell function in vivo exist, methods to deliver therapeutics to β cells are lacking. We leveraged the rare ability of β cells to concentrate zinc to preferentially trap zinc-binding molecules within β cells, resulting in β-cell-targeted compound delivery. We determined that zinc-rich β cells and islets preferentially accumulated TSQ (6-methoxy-8-p-toluenesulfonamido-quinoline) in a zinc-dependent manner compared with exocrine pancreas. Next, we asked whether appending a zinc-chelating moiety onto a β-cell replication-inducing compound was sufficient to confer preferential β-cell accumulation and activity. Indeed, the hybrid compound preferentially accumulated

SUBMITTER: Horton TM 

PROVIDER: S-EPMC6386607 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature