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Biochem Biophys Res Commun. 1994 Nov 30;205(1):417-22.

Obese Zucker (fa/fa) rats are resistant to insulin's inhibitory effect on hepatic apo B secretion.

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Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.


Hepatocytes derived from lean Zucker rats have reduced secretion of apo B and lowered cellular apo B in response to a physiologic range of insulin (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. Decreased sensitivity and responsiveness of hepatocytes derived from obese rats suggests insulin resistance and dose-response curves are consistent with coexistent binding and post-binding defects. Inability to inhibit hepatic apo B secretion in the presence of short-term high levels of insulin may have important implications to the balance of intestinal and hepatic triglyceride-rich lipoprotein secretion post-prandially.

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