Anti-apoptotic effect of insulin on normal hepatocytes in vitro and in vivo |
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Authors: | M. Bilodeau J. Tousignant C. Éthier B. Rocheleau V.-A. Raymond R. Lapointe |
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Affiliation: | 1. Laboratoire d'hépatologie cellulaire, Centre de recherche du Centre hospitalier de l', Université de Montréal-H?pital Saint-Luc, USA 2. Département de chirurgie, Centre de recherche du Centre hospitalier de l'Université de Montréal-H?pital Saint-Luc, USA
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Abstract: | Liver growth factors are known to be anti-apoptotic for hepatocytes. The potential of insulin, a liver co-mitogen, has not been thoroughly evaluated. We studied the anti-apoptotic role of insulin on primary cultures of rat hepatocytes exposed to transforming growth factor-beta (TGF-beta) as the apoptotic agent and in the left portal vein ligation model (LVPL) of liver atrophy. Results show that insulin decreases apoptosis of TGF-beta-treated hepatocyte cultures by 43% (P < 0.002) and the alanine amino transferase (ALT) release by 49% (P < 0.001). Left lobes of LPVL animals displayed a significant increase in the levels of TGF-beta mRNA. In LPVL rats receiving continuous infusion of insulin in the left lobes, the weight of the atrophic lobes was higher over a 7-day period in comparison to control animals. This was associated with lower levels of serum ALT and with a five-fold decrease in the apoptotic index in the left lobes (P < 0.0001). Induction of Akt phosphorylation and increased expression of Bcl-xl were observed in the left lobes of insulin-treated animals. In conclusion, these results show that insulin is anti-apoptotic for normal hepatocytes both in vitro and in vivo and that the action of insulin is associated with increased Bcl-xl expression and Akt activation. |
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Keywords: | Akt apoptosis Bcl-xl growth factors insulin left portal vein ligation |
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