Pioneer Valley Life Science Institute, University of Massachusetts-Amherst, Springfield, MA, USA.
Islets. 2011 Nov-Dec;3(6):367-75. doi: 10.4161/isl.3.6.18013. Epub 2011 Nov 1.
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.
TGFß 超家族成员，包括激活素和 TGFß，在体外使用大鼠胰岛调节葡萄糖刺激的胰岛素分泌 (GSIS)，而体内减少 TGFß 超家族信号转导的基因操作导致胰岛发育不良和/或高血糖。此外，激活素和肌生成抑制素的拮抗剂 Fstl3 的缺失导致胰岛增大和ß细胞增生。这些研究表明，内源性 TGFß 超家族配体调节ß细胞的生成和/或功能。为了验证这一假说，我们研究了分离的大鼠和小鼠胰岛中内源性 TGFß 配体的合成和作用。我们发现激活素 A、TGFß1 和肌生成抑制素处理增强了大鼠胰岛的 GSIS，但在小鼠胰岛中没有一种测试的配体增强了 GSIS。然而，卵泡抑素抑制 GSIS，这与内源性 TGFß 超家族配体在调节胰岛素分泌中的作用一致。TGFß 超家族成员在大鼠和小鼠胰岛中的表达不同，肌生成抑制素在小鼠胰岛中高度表达，而在大鼠中不可检测。这些结果表明，TGFß 超家族成员以物种特异性的方式直接调节胰岛功能，而胰岛产生的配体在小鼠和大鼠之间存在差异。这些配体在体外对小鼠胰岛没有作用可能是机械的，也可能是由于这些配体的物种特异性作用。
