Nov 1, 1991

Nutrition and somatomedin. XXVI. Molecular regulation of IGF-I by insulin in cultured rat hepatocytes

Diabetes
L S PhillipsC I Pao

Abstract

Although decreased levels of circulating insulinlike growth factor I (IGF-I) and hepatic IGF-I mRNA in diabetic animal models support a role for insulin in IGF-I regulation, it has been difficult to study the effects of insulin in vitro. Few immortal cell lines exhibit hormone-responsive production of IGF-I, and studies of cultured hepatocytes have often been inconclusive because conventional methods may not reproduce the IGF-I transcripts recognized in vivo. We have modified the hepatocyte isolation and RNA extraction procedures to circumvent this problem, resulting in transcripts of 1, 2, and 7.5 kb. With increasing insulin from 10(-10) to 10(-6) M, dexamethasone from 10(-10) to 10(-7) M, and amino acids from 1 to 10 x rat arterial levels, IGF-I release rose by 226, 257, and 447%, respectively (P less than 0.05), with correlated changes in IGF-I mRNA (r = 0.75, P less than 0.005). In the presence of 5 x amino acids and 10(-7) M dexamethasone, insulin-stimulated IGF-I release was dose dependent, increasing 183% at 10(-6) M (P less than 0.01). Across a broad range of amino acid concentrations (0.25-6.25 x), insulin provided consistent stimulation of both IGF-I mRNA content and release of IGF-I. Cells cultured for 2 days at 10(-...Continue Reading

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Mentioned in this Paper

Insulin-Like Growth Factor I
Recombinant Insulin-Like Growth Factor
Somatomedin Assay
Amino Acids, I.V. solution additive
August Rats
Somatomedins
Hepatic
Novolin
Hyperinsulinism
Northern Blot

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