AJP - Cell Physiology, Vol 260, Issue 5 C1046-C1051, Copyright © 1991 by American Physiological Society
TGF-beta stimulates insulin secretion and blocks mitogenic response of pancreatic beta-cells to glucose
A. Sjoholm and C. Hellerstrom
Department of Medical Cell Biology, Uppsala University, Sweden.
The long-term influence of transforming growth factor-beta (TGF-beta) on
replication and insulin secretion by insulin-producing pancreatic
beta-cells was investigated. For this purpose, fetal rat pancreatic islets
containing a high proportion of beta-cells were isolated and maintained in
tissue culture for 3 days at different concentrations of TGF-beta. TGF-beta
(5-500 pM) at a glucose concentration of 11.1 mM did not affect the
replication of the beta-cells or their insulin content but enhanced
secretion of insulin from these cells. TGF-beta (500 pM) counter-acted the
mitogenic action of 16.7 mM glucose but failed to affect the
glucose-induced increase in islet insulin content or secretion. Growth
hormone (GH) also stimulated beta-cell DNA synthesis and insulin secretion,
but TGF-beta was unable to prevent these effects. It was found, moreover,
that TGF-beta did not prevent the increase in islet polyamine content which
occurred in response to glucose or GH, indicating that the effects of
TGF-beta are not mediated through this pathway. Addition of neutralizing
antibodies to TGF-beta did not affect the mitogenic or secretory responses
to glucose or GH, suggesting that TGF-beta does not exert any autocrine or
paracrine function in islets.
