Besitzt die Proinsulinverunreinigung kommerzieller Insulinpräparate Bedeutung für die Stimulierung von Insulinantikörpern?

Kerp, L.; Steinhilber, S.; Kasemtr, H.

doi:10.1007/bf01583916

Cited by 10 publications

(2 citation statements)

References 4 publications

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“…Commercial preparations of mixtures of bovineporcine insulin have small and variable amounts of contaminating bovine and porcine proinsulin (17)(18)(19)(20). The se(quences of the C-segments of the precursor molecules differ from each other and from their human counterpart to a much larger extent than the insulin A and B chains (18,21,22) and have been shown to be potent antigens in both experimental animals (23)(24)(25)(26) and humans (27)(28)(29)(30). A survey of insulin-treated diabetic patients demonstrated specific proinsulin antibodies in 80% of the cases (29).…”

Section: Discussionmentioning

confidence: 99%

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

Goldman¹,

Baldwin²,

Rubenstein³

et al. 1979

J. Clin. Invest.

137

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A B S T R A C T Five patients with fasting and(or) postprandial hypoglycemia were found to have insulin antibodies in the absence of previously documented immunization. Studies on the equilibrium-binding of insulin to the autoantibodies revealed two classes of binding sites with association constants and binding capacities analogous to those of insulin antibodies from insulin-treated diabetic patients. Similarly, no consistent differences in these parameters were found in both groups of patients with insulins ofbovine, porcine, and human origin. Proinsulin (C-segment directed) antibodies capable ofbinding bovine or porcine proinsulin were present in 10 of 10 and 9 of 10 insulin-treated diabetics serving as controls, respectively, and, when present, provide incontrovertible evidence of exogenous insulin administration. No such antibodies could be detected in the hypoglycemic patients with autoimmune insulin antibodies.The kinetics of dissociation of the insulin-antibody complexes were consistent with the existence of two classes of antibody sites. The corresponding dissociation rate constants were large enough to predict that significant amounts of free hormone may be generated by this mechanism and provide a plausible pathogenesis for the hypoglycemia in these patients.

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Section: Discussionmentioning

confidence: 99%

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

Goldman¹,

Baldwin²,

Rubenstein³

et al. 1979

J. Clin. Invest.

137

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“…administration of proinsulin, present in therapeutic insulin will induce proinsulin-specific antibodies in diabetie patients. Although a small concentration of such antibodies have been demonstrated in a pooled human sera (Kerp, Steinhilber and Kasemir 1970), their ineidence in the individual patients remains uninvestigated.…”

mentioning

confidence: 99%

The Prevalence of Proinsulin-Specific Antibodies in Diabetic Patients

Kumar

1973

Horm Metab Res

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To establish the prevalence of proinsulin-specific antibodies in diabetic patients, thirty serum sampies were analyzed.Among the insulin-treated group, proinsulin antibodies were demonstrated in 20 cases (80%) by the significant binding of 1251-bovine proinsulin to the sera pretreated with excess of insulin and reduced binding when these sera were preincubated with unlabelled bovine proinsulin. Five other sera (20%) bound tracer pro insulin, but did not bind significantly after preincubation with insulin indicating tbat only cross-reacting insulin antibodies were present and there were no detectable proinsulin antibodies. Sera from five diet-controlled patients bad no antibodies. IntroduetionComrnercia! preparations of insulin contain variable amounts of proinsulin and related substances (Steiner, HaI/und, Rubenstein, Cho and Bayliss 1968, Chance 1972) which have been shown to have significant immunogenicity in anima! experiments (Rubenstein, Steiner, Lawrence and Kirsteins 1969, Kerp 1971, Schlichtkrull, Brange, Christiansen, Hallund, Heding and Jorgensen 1972. I t is very likely that the daily administration of proinsulin, present in therapeutic insulin will induce proinsulin-specific antibodies in diabetie patients. Although a small concentration of such antibodies have been demonstrated in a pooled human sera (Kerp, Steinhilber and Kasemir 1970), their ineidence in the individual patients remains uninvestigated.The purpose of this report is to establish the prevalence of proinsulin-specific antibodies in diabetic patients. Materials and MethodsFisher Endocrinology Laboratories, Chicago) were purified by gel filtration (Sephadex G-50, 0.5 x 20 in. column, borate buffer pH 7.4) and diluted to 0.2 ng/mL The same preparations of labelIed tracers were used for alI the tests.80vine proinsulin (lot no. 615-10708-212-2) and insulin (lot no. 615-10828-244) were supplied by Dr. R. Chance, Lilly Research Laboratories, Indianapolis. These proteins were dissolved in borate buffer, pH 7.4, containing 1% bovine serum albumin (Mann Laboratories, New York) and diluted to 500 ng/mL Anti-human immunoglobulin serum (AHI-RS) was prepared by hyperimmunizing rabbits to purified plasma Cohn fraction 11. This sera reacted strongly with both the antigenie types K and A light chains and was therefore a polyvalent anti-immunoglobulin (Feinstein, Rapaport and Chong 1969). A seven-fold concentration of this sera produced maximal precipitation of immunoglobulins.Detection of proinsulin and insulin antibodies: Two sets of tubes, each containing 0.1 ml of diluted (1: 16) serum were preincubated for 20 hr at 4 0 C with 0.1 ml of buffer, insulin (500 ng/mq or proinsulin (500 ng/ml). To one set of tubes, 0.1 ml of I 51-bovine proinsulin (0.2 ng/ml) and to the other set, 0.1 ml of 12SI_bovine insulin (0.2 !Jg/ml) were added. Tubes were reincubated for 40 hr at 4 0 C. To precipitate the immune complexes, 0.1 ml of AHI-RS 0:2) was then added. Forty hours later precipitate was filtered and washed on oxoid membrane (Amersham Searle). The radi...

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Insulin Allergy, “Cellular” Antibodies and Insulitis

Federlin¹

1975

Insulin

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Besitzt die Proinsulinverunreinigung kommerzieller Insulinpräparate Bedeutung für die Stimulierung von Insulinantikörpern?

Cited by 10 publications

References 4 publications

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

Characterization of circulating insulin and proinsulin-binding antibodies in autoimmune hypoglycemia.

The Prevalence of Proinsulin-Specific Antibodies in Diabetic Patients

Insulin Allergy, “Cellular” Antibodies and Insulitis

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