Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes …

JF Caro, O Ittoop, WJ Pories… - The Journal of …, 1986 - Am Soc Clin Investig
JF Caro, O Ittoop, WJ Pories, D Meelheim, EG Flickinger, F Thomas, M Jenquin…
The Journal of clinical investigation, 1986Am Soc Clin Investig
We have developed a method to isolate insulin-responsive human hepatocytes from an
intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from
obese patients with noninsulin-dependent diabetes were resistant to maximal insulin
concentration, and those from obese controls to submaximal insulin concentration in
comparison to nonobese controls. Insulin binding per cell number was similar in all groups.
However, insulin binding per surface area was decreased in the two obese groups because …
We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per cell number was similar in all groups. However, insulin binding per surface area was decreased in the two obese groups because their hepatocytes were larger. In addition, the pool of detergent-extractable receptor was further decreased in diabetics. Insulin receptors in all groups were unaltered as determined by affinity-labeling methods. However, insulin-stimulated insulin receptor kinase activity was decreased in diabetics. Thus, in obesity, decreased surface binding could explain resistance to submaximal insulin concentrations. In diabetes, diminished insulin-stimulated protein kinase activity and decreased intracellular pool of receptors could provide an explanation for postinsulin-binding defect(s) of insulin action in human liver.
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The Journal of Clinical Investigation