Experimental diabetes mellitus was induced in adult male and female rats by injecting streptozocin (STZ; 60 mg/kg i.p.) in preparation for a screening survey of changes in the pattern of undenatured plasma proteins, as revealed by two-dimensional (2-D) gel electrophoresis followed by silver staining. As early as 8–12 days later, the 2-D gels revealed three high-molecular-weight plasma protein spots, which persisted for 150 days in the blood of untreated diabetic rats. Such spots were not seen in plasma of normal control rats. Evidence is presented for the presumptive characterization of these proteins as oligomers of immunoglobulin A (IgA). Specific measurement of total IgA content of diabetic plasma samples by single-radial immunodiffusion, after reduction with dithiothreitol and alkylation with iodoacetamide, reveals that IgA content increases linearly from control values of 11.1 ± 4.6 to 358 ± 249 mg/dl (means ± SE) 21 days after STZ and persists at these high levels for as long as 150 days. Diabetic rats injected daily with insulin showed IgA levels only two to four times higher than normal. Neither experiments designed to quantitate the rates of clearance (catabolism plus excretion) of 125I-labeled secretory IgA from the circulation of normal and diabetic rats nor measurement of total IgA in the bile from diabetic and normal bile fistula rats supports the view that slowed clearance from the circulation or impaired biliary excretion in the diabetic rat causes observed gross hyperimmunoglobulinemia A.

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