Activin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity

作者：Bonomi Lara; Brown Melissa; Ungerleider Nathan; Muse Meghan; Matzuk Martin M; Schneyer Alan^*

来源：American Journal of Physiology - Endocrinology And Metabolism, 2012, 303(5): E587-E596.

DOI：10.1152/ajpendo.00177.2012

• myostatin
• beta-cell
• alpha-cell
• follistatin
• activin A

Bonomi L, Brown M, Ungerleider N, Muse M, Matzuk MM, Schneyer A. Activin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity. Am J Physiol Endocrinol Metab 303: E587-E596, 2012. First published June 26, 2012; doi:10.1152/ajpendo.00177.2012.-Based on the phenotype of the activin-like kinase-7 (ALK7)-null mouse, activins A and B have been proposed to play distinct roles in regulating pancreatic islet function and glucose homeostasis, with activin A acting to enhance islet function and insulin release while activin B antagonizes these actions. We therefore hypothesized that islets from activin B-null (BBKO) mice would have enhanced glucose-stimulated insulin secretion. In addition, we hypothesized that this enhanced islet function would translate into increased whole body glucose tolerance. We tested these hypotheses by analyzing glucose homeostasis, insulin secretion, and islet function in BBKO mice. No differences were observed in fasting glucose or insulin levels, glucose tolerance, or insulin sensitivity compared with weight-matched young or older males. Similarly, there were no significant differences in insulin secretion comparing islets from WT or BBKO males at either age. However, BBKO islets were more sensitive to activin A, myostatin (MSTN), and follistatin (FST) treatments, so that activin A and FST inhibited and MSTN enhanced glucose stimulated insulin secretion. While mean islet area and the distribution of islet areas were not different between the genotypes, islet mass, islet number, and the proportion of alpha-cells/islet were significantly reduced in BBKO islets. These results indicate that activin B does not antagonize activin A to influence whole body glucose homeostasis or beta-cell function but does influence islet mass and proportion of alpha-cells/islet. Therefore, loss of activin B signaling alone does not account for the ALK7-null phenotype, but activin B may have important roles in modulating islet mass, islet number, and the cellular composition of islets.

• 出版日期2012-9