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. 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.
Sjöholm
A
A
Department of Medical Cell Biology, Uppsala University, Sweden.
Hellerström
C
C
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D005333:Fetus; D005947:Glucose / Q000494:pharmacology*; D013006:Growth Hormone / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007328:Insulin; D011073:Polyamines; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D013006:Growth Hormone; D005947:Glucose