Diabetes, Vol 39, Issue 6 728-733, Copyright © 1990 by American Diabetes Association

ARTICLES

Persistent cutaneous insulin allergy resulting from high-molecular-weight insulin aggregates

RE Ratner, TM Phillips and M Steiner
Department of Medicine, George Washington University Medical Center, Washington, DC 20037.

Cutaneous insulin allergy remains a clinical problem despite the use of highly purified human insulins. We used in vitro lymphocyte-transformation studies to examine the reactivity of various insulin formulations in diabetic patients with (n = 4) and without (n = 8) cutaneous allergies. Nonspecific response to concanavalin A demonstrated a greater than 40-fold response in both groups. Control patients did not respond to the addition of commercial insulin preparations (stimulation index [SI] less than 4), whereas allergic patients had an 11-fold response to beef (P less than 0.01), a 10-fold response to pork (P less than 0.01), and a 6-fold response to human (P less than 0.01) insulins. This response was limited to a single insulin manufacturer's preparations and was uniform in all three species tested. Efforts to identify the offending agent revealed no lymphoblast transformation when crystalline insulin was used or when commercial preparations were purified to a single peak by high-performance liquid chromatography (HPLC). Pure crystalline insulin dimers of beef, pork, and human species were tested; control subjects responded with mean SIs of 1.9, 1.9, and 1.8, respectively, whereas allergic patients showed greater reactivity to beef (SI 7.3) and pork (SI 14.8). The lymphoblast-transformation response to crystalline human dimer was dose dependent with mean SIs of 0.9 at low concentration (2.8 ng/ml) and 19.2 at a higher concentration (20.4 ng/ml). The commercial insulin preparations were run on size-exclusion HPLC to determine high-molecular-weight aggregate content. Independent of species, a single manufacturer had products demonstrating aggregate levels 3- to 6-fold higher than those found in other manufacturers' preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. E. Fineberg, T. T. Kawabata, D. Finco-Kent, R. J. Fountaine, G. L. Finch, and A. S. Krasner Immunological Responses to Exogenous Insulin Endocr. Rev., October 1, 2007; 28(6): 625 - 652. [Abstract] [Full Text] [PDF]

				S. M. Park, K. J. Ahn, H. Y. Jung, J. H. Park, and J. Kim Effects of novel peptides derived from the acidic tail of synuclein (ATS) on the aggregation and stability of fusion proteins Protein Eng. Des. Sel., March 1, 2004; 17(3): 251 - 260. [Abstract] [Full Text] [PDF]

				S. E. Fineberg, J. Huang, R. Brunelle, K. S. Gulliya, and J. H. Anderson Jr Effect of Long-Term Exposure to Insulin Lispro on the Induction of Antibody Response in Patients With Type 1 or Type 2 Diabetes Diabetes Care, January 1, 2003; 26(1): 89 - 96. [Abstract] [Full Text] [PDF]

				R. J. St. John, J. F. Carpenter, C. Balny, and T. W. Randolph High Pressure Refolding of Recombinant Human Growth Hormone from Insoluble Aggregates. STRUCTURAL TRANSFORMATIONS, KINETIC BARRIERS, AND ENERGETICS J. Biol. Chem., December 7, 2001; 276(50): 46856 - 46863. [Abstract] [Full Text] [PDF]

				R. J. St. John, J. F. Carpenter, and T. W. Randolph High pressure fosters protein refolding from aggregates at high concentrations PNAS, November 9, 1999; 96(23): 13029 - 13033. [Abstract] [Full Text] [PDF]