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

TitleActivin B regulates islet composition and islet mass but not whole body glucose homeostasis or insulin sensitivity.
Publication TypeJournal Article
Year of Publication2012
AuthorsBonomi L, Brown M, Ungerleider N, Muse M, Matzuk MM, Schneyer A
JournalAm J Physiol Endocrinol Metab
Volume303
Issue5
PaginationE587-96
Date Published2012 Sep 1
ISSN1522-1555
KeywordsActivins, Aging, Animals, Blood Glucose, Cell Count, Follistatin, Glucagon-Secreting Cells, Homeostasis, Inhibin-beta Subunits, Insulin, Insulin Resistance, Islets of Langerhans, Male, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Myostatin, Organ Size, Tissue Culture Techniques
Abstract

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 α-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 β-cell function but does influence islet mass and proportion of α-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.

DOI10.1152/ajpendo.00177.2012
Alternate JournalAm. J. Physiol. Endocrinol. Metab.
PubMed ID22739106