Somatostatin-14 blocks the hepatotrophic effects of insulin in the rat.
We hypothesized that somatostatin-14 (SS-14) might inhibit insulin-stimulated hepatic growth. Rat hepatocytes were isolated by a two-step collagenase perfusion technique and cultured on Matrigel. Differentiated hepatocyte function was documented by albumin synthesis. Hepatocytes were incubated with insulin in the presence or absence of SS-14. Hepatocyte proliferation was assessed by tritiated thymidine ([3H]thy) incorporation into DNA. [3H]thy incorporation was increased by 230% in the presence of insulin and was essentially abolished by the addition of SS-14. Insulin-stimulated cyclic-AMP accumulation was also decreased from 190 to 108% of control levels (P less than 0.05) by the addition of SS-14. Pretreatment with pertussis toxin, which inactivates the inhibitory G-protein, Gi, blocked the effect of SS-14.


CONCLUSIONS
(i) In the rat, SS-14 effectively blocks insulin-stimulated [3H]thy incorporation into DNA, possibly by blocking intracellular cAMP accumulation. (ii) Pertussis toxin blocks the growth inhibitory effects of SS-14, suggesting that inhibitory G proteins are involved in the mechanism of SS-14 action. Somatostatin may be useful in studying the role of second messengers in cell growth.
Raper
S E
SE
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109.
Kothary
P C
PC
Kokudo
N
N
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007329:Insulin Antagonists; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D037342:Pertussis Toxin; D013004:Somatostatin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007328:Insulin; D007329:Insulin Antagonists; D010566:Virulence Factors, Bordetella; D013004:Somatostatin; D004247:DNA; D000242:Cyclic AMP; D037342:Pertussis Toxin