Obese Zucker (fa/fa) rats are resistant to insulin's inhibitory effect on hepatic apo B secretion.
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.
Sparks
J D
JD
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Sparks
C E
CE
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002478:Cells, Cultured; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
D001055:Apolipoproteins B; D007328:Insulin