Differential synthesis and action of TGFß superfamily ligands in mouse and rat islets.

TitleDifferential synthesis and action of TGFß superfamily ligands in mouse and rat islets.
Publication TypeJournal Article
Year of Publication2011
AuthorsBrown ML, Kimura F, Bonomi LM, Ungerleider NA, Schneyer AL
JournalIslets
Volume3
Issue6
Pagination367-75
Date Published2011 Nov-Dec
ISSN1938-2022
KeywordsActivins, Animals, Glucose, Immunohistochemistry, Insulin, Islets of Langerhans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Myostatin, Proteins, Rats, Rats, Inbred Lew, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Species Specificity, Transforming Growth Factor beta
Abstract

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.

DOI10.4161/isl.3.6.18013
Alternate JournalIslets
PubMed ID21964310