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Two new radioimmunoassays for human proinsulin (hPI) have been developed and used to study patients with islet cell tumors and familial hyperproinsulinemia. Both antisera were adsorbed against human C-peptide conjugated to Sepharose, following which cross-reactivity to insulin and C-peptide was less than 0.001%. Antiserum 18D recognized the junction between the insulin B-chain and C-peptide and provided fivefold greater sensitivity than our previously reported hPI assay. Antiserum 11E recognized a determinant which includes or is adjacent to the A-chain-C-peptide junction or which is specified by the tertiary structure. In all 20 patients studied with surgically confirmed islet cell tumors, fasting plasma proinsulinlike material (PLM) was abnormal (greater than 3 SD from the mean measured in either lean or obese subjects) in both assays. This provided better discrimination than has been reported for PLM measured by gel filtration (abnormal in 13 of 14 of the present samples) with a considerably less laborious procedure. Samples from two families in which a mutant proinsulin is present in the circulation have immunoreactivity in the two assays consistent with previous identification of the molecule as an A-chain-C-peptide-linked intermediate of proinsulin conversion. The immunoreactivity of a sample from another family in which large amounts of proinsulin circulate are consistent with an intact molecule being the predominant form. This assay will be useful for confirming the diagnosis of insulin-secreting tumor in patients suspected of recurrent fasting hypoglycemia and in physiologic studies of proinsulin secretion.
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
June 1979,
Proceedings of the National Academy of Sciences of the United States of America,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
March 1984,
The Journal of clinical investigation,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
September 1984,
The New England journal of medicine,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
July 1985,
The Journal of clinical investigation,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
October 1989,
Diabetes care,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
September 2003,
Molecular endocrinology (Baltimore, Md.),
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
August 1989,
Endocrinologia japonica,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
October 2004,
Clinical endocrinology,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
April 1976,
The New England journal of medicine,
R M Cohen, and
B D Given, and
J Licinio-Paixao, and
S A Provow, and
P A Rue, and
B H Frank, and
M A Root, and
K S Polonsky, and
H S Tager, and
A H Rubenstein
May 1971,
The New England journal of medicine,
