Members of the TGFß superfamily, including
activins and TGFß, modulate
glucose-stimulated insulin secretion (GSIS) in vitro using rat islets while genetic manipulations that reduce TGFß superfamily signaling in vivo in mice produced hypoplastic islets and/or
hyperglycemia. Moreover, deletion of Fstl3, an antagonist of
activin and
myostatin, resulted in enlarged islets and ß-cell
hyperplasia. These studies suggest that endogenous TGFß superfamily
ligands regulate ß-cell generation and/or function. To test this hypothesis, we examined endogenous TGFß
ligand synthesis and action in isolated rat and mouse islets. We found that
activin A, TGFß1, and
myostatin treatment enhanced rat islet GSIS but none of the
ligands tested enhanced GSIS in mouse islets. However,
follistatin inhibited GSIS, consistent with a role for endogenous TGFß superfamily
ligands in regulating insulin secretion. Endogenous expression of TGFß superfamily members was different in rat and mouse islets with
myostatin being highly expressed in mouse islets and not detectable in rats. These results indicate that TGFß superfamily members directly regulate islet function in a species-specific manner while the
ligands produced by islets differ between mice and rats. The lack of in vitro actions of
ligands on mouse islets may be mechanical or result from species-specific actions of these
ligands.