AJP - Gastrointestinal and Liver Physiology, Vol 247, Issue 2 155-G160, Copyright © 1984 by American Physiological Society
Regulation of pancreatic acinar cell insulin receptors by insulin
J. Mossner, C. D. Logsdon, I. D. Goldfine and J. A. Williams
In vivo pancreatic acini from normal mice are exposed to very high
concentrations of insulin. To determine whether insulin receptors in these
acini are downregulated by this endogenous insulin, insulin receptors on
acini from both normal and diabetic mice were studied. Isolated acini from
normal mice, which have accompanying islets of Langerhans, were studied
under conditions where endogenous insulin was minimized. These acini bound
50% less 125I-insulin than acini from mice made diabetic with
streptozotocin. Computer analysis of competition-inhibition curves showed a
decrease in the number of insulin receptors in acini from normal mice when
compared with acini from diabetic mice; however, the IC50 (a measure of
receptor affinity) remained unchanged at approximately 1 nM. To study
further the regulation of acinar cell insulin receptors, acini from
diabetic mice were placed in suspension culture for 24 h. Addition of 1
microM insulin during the culture period led to a 30% decrease in
subsequent 125I-insulin binding; the presence or absence of either
epidermal growth factor or carbachol was without effect on insulin binding.
The decrease in binding induced by insulin resulted from a change in
receptor number without an alteration of the IC50. Measurement of total
acinar cell insulin receptors by solubilization of these acini in 1% Triton
X-100 showed that this insulin-induced decrease was due to a change in the
total number of cellular insulin receptors. The present study suggests,
therefore, that insulin can regulate its own receptor on pancreatic acini
and that in vivo insulin receptors in normal pancreatic cells are
downregulated, presumably due to high ambient insulin concentrations.
