Activin A stimulates insulin secretion in cultured human pancreatic islets

Abstract

Activin A is a dimeric glycoprotein showing a high sequence homology with transforming growth factor-beta (TGF-beta) and playing autocrine/paracrine actions in reproductive tissues. However, since the synthesis of activin is ubiquitous it may have a role in regulating cell growth and differentiation in several tissues. Previous studies showed that activin A is expressed by insulin-positive B cells of human pancreatic islets, and women with gestational diabetes have higher serum activin A levels than healthy pregnant women at the same gestational age. The present study aimed to evaluate the effect of activin A on insulin secretion from cultured human pancreatic islets. With this purpose human pancreatic islets were incubated with varying concentrations of activin A (0.1 to 10.0 nM). In absence of glucose, activin A did not modify insulin secretion at the different concentrations used. In absence of activin A, 8.3 mM and 16.7 mM glucose significantly increased insulin secretion, with a dose-dependent pattern. In presence of a non stimulatory concentration of glucose (3.3 mM), activin A significantly increased insulin secretion starting from low concentration (0.1 nM). Furthermore, the addition of activin A to 8.3 mM and 16.7 mM glucose induced an additional effect of the dose-dependent glucose-mediated insulin secretion (p<0.001). The present data could support a role for activin A in human endocrine pancreas in modulating insulin response to different glucose concentrations.

Reciprocal modulation of adult beta cell maturity by activin A and follistatin

“…Acute activin A treatment of cultured rat and human islets was reported to increase insulin secretion [21,22]; however acutely treated MIN6 cells did not show increased secretion [29]. In our study, activin A had no acute stimulatory effect on glucose-stimulated insulin secretion in perifused isolated mouse islets, while prolonged activin A treatment significantly decreased insulin secretion.…”

“…Insulin secretion was also 14.5% lower from activin Atreated human islets (M. Szabat, unpublished data). Since previous studies have reported that acute activin A treatment of cultured rat and human islets increased insulin secretion [21,22], we also examined the acute effects of 4 nmol/l activin A in perifused mouse islets (Fig. 5c).…”

“…Activins control embryonic patterning of foregut-derived organs [19], have important roles in pancreatic development [20] and have been implicated in the control of insulin secretion [21,22]. Activins and their receptors are present in the developing pancreas and adult islet cells [23,24].…”

Differential regulation of mouse pancreatic islet insulin secretion and Smad proteins by activin ligands

“…Earlier studies indicated that activin A enhances insulin secretion [12,13,37]. However, more recent work reported that activin A has either no effect [4] or in fact decreases [15,16] GSIS by islets.…”

“…Immunohistochemical studies have localised activin A predominantly to alpha cells, while activin B was shown to be expressed by both alpha and beta cells [4]. Earlier work showed that exogenous activin A can increase the cytoplasmic free Ca 2+ concentration and stimulate insulin secretion in human and rat pancreatic islets, even at low levels of ambient glucose [12][13][14]. Those results have been challenged by more recent studies indicating that in mouse islets, activin A either has no effect [4] or may in fact decrease GSIS [15,16].…”