Pancreatic hormone receptors on islet cells.
To assess whether islet cells are equipped with recognition units which allow an intra-islet regulation via released hormones, the presence of insulin and glucagon receptors is investigated on purified pancreatic A and B cells. Mono-[125I]glucagon is shown to bind specifically to islet B cells, with similar binding characteristics as in isolated hepatocytes but involving less receptors per cell (2.10(4) per B cell vs. 8.10(5) per liver cell). Binding is half-maximally displaced by 5.10(-9) M glucagon, a concentration known to induce half-maximal biological effects in isolated B cells. These results are compatible with a regulatory role of glucagon in the insulin release process. No specific binding of [125I]tyr-A14-insulin is detected on pancreatic A cells. In order to increase receptor assay sensitivity, [123I]tyr-A14-insulin is prepared with at least 5-fold higher specific activity. Its validity for in vitro receptor analysis is demonstrated in IM-9 lymphocytes, where insulin binding is detectable down to 10(4) cells/ml. However, no insulin-binding sites are identified on pancreatic A cells, even at 10(6) cells/ml. If isolated A cells contain high affinity insulin receptors, their number should be inferior to 400 per cell, which is 50- to 500-fold lower than in classical insulin target cells. These findings explain the insensitivity of the glucagon release process to acute exposure to insulin.
Van Schravendijk
C F
CF
Foriers
A
A
Hooghe-Peters
E L
EL
Rogiers
V
V
De Meyts
P
P
Sodoyez
J C
JC
Pipeleers
D G
DG
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018027:Receptors, Glucagon
D007328:Insulin; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; C029491:insulin, 3-iodo-Tyr(A14)-; D005934:Glucagon; D011972:Receptor, Insulin