TGF-BETA STIMULATES INSULIN-SECRETION AND BLOCKS MITOGENIC RESPONSE OF PANCREATIC BETA-CELLS TO GLUCOSE

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 (500 pM). 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) counteracted 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.