Diabetes, Vol 40, Issue 7 837-841, Copyright © 1991 by American Diabetes Association
Nutrition and somatomedin. XXV. Regulation of insulinlike growth factor binding protein 1 in primary cultures of normal rat hepatocytes
BC Villafuerte, S Goldstein, LJ Murphy and LS Phillips
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30303.
Although mRNAs encoding insulinlike growth factor (IGF) binding proteins
(BPs) are present in adult rat liver and IGF BP-1 circulates at elevated
levels in diabetic animals, there is little knowledge of the metabolic
regulation of IGF BPs in normal tissues. We examined the release of IGF BPs
by adult rat hepatocytes maintained in primary culture. When cultured for 2
days in the absence of added insulin, hepatocytes released a BP identified
as BP-1 on the basis of approximately 30,000-Mr on ligand blotting and
reactivity with antiserum to human BP-1 in immunoblotting and
immunoprecipitation studies. Release of BP-1 was sensitive to insulin with
suppression of 24 +/- 4, 73 +/- 5, and 64 +/- 14% at 10(-10), 10(-8), and
10(-6) M insulin, respectively; ED50 was approximately 1.7 x 10(-9) M,
which is within the physiological range. Suppression by insulin was
reversible and began within 3 h. Because normal hepatocytes in primary
culture exhibit insulin-responsive release of both BP-1 and IGF-1, this
system may be an ideal model for studies of molecular mechanisms of
metabolic regulation.