OBESE ZUCKER (FA FA) RATS ARE RESISTANT TO INSULINS INHIBITORY EFFECTON HEPATIC APO-B SECRETION/

Hepatocytes derived from lean Zucker rats have reduced secretion of ap o B and lowered cellular apo B in response to a physiologic range of i nsulin (0.1 nM - 10 nM). Effects are attenuated in hepatocytes derived from Zucker obese rats and seen only at higher insulin concentrations (>100 nM) with a significant shifting of the dose-response curve. Dec reased sensitivity and responsiveness of hepatocytes derived from obes e rats suggests insulin resistance and dose-response curves are consis tent with coexistent binding and post-binding defects. Inability to in hibit hepatic apo B secretion in the presence of short-term high level s of insulin may have important implications to the balance of intesti nal and hepatic triglyceride-rich lipoprotein secretion post-prandiall y. (C) 1994 Academic Dress, Inc.