Proliferation of adult rat hepatocytes in primary culture induced by insulin is potentiated by cAMP-elevating agents

European Journal of Pharmacology
M Kimura, Masahiko Ogihara

Abstract

We investigated whether or not insulin and cAMP-elevating agents induce the proliferation of adult rat hepatocytes during the early and late phases of primary culture. Adult rat hepatocytes synthesized a significant amount of DNA when cultured in the presence of 10(-7) M insulin for 3 h. Under these conditions, the number of nuclei increased within 4 h. Hepatocyte DNA synthesis and proliferation were not essentially affected by the initial plating densities. Other cAMP-elevating agents, such as glucagon, forskolin and dibutyryl cAMP, as well as beta-adrenoceptor agonists (i.e., metaproterenol and isoproterenol) alone had no effect on either hepatocyte DNA synthesis or proliferation in primary culture. In contrast, these agents potentiated both processes at concentrations as low as 10(-7) M when cultured in combination with 10(-7) M insulin. The stimulatory effects of beta-adrenoceptor agonists and other cAMP-elevating agents were significantly blocked by the cAMP-dependent protein kinase inhibitor, H-89 (N-[2-(p-(bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10(-7) M). The mitogenic effect of insulin upon hepatocytes was almost completely suppressed by genistein (5 x 10(-6) M), wortmannin (10(-7) M) and b...Continue Reading

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Citations

Apr 28, 2000·Gastroenterology·F SchliessD Häussinger
Nov 6, 2001·The Journal of Biological Chemistry·Matthew N PoySonia M Najjar
Aug 7, 2003·American Journal of Physiology. Endocrinology and Metabolism·Ilham El-KhattabiBrigitte Reusens

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