title: Altered insulin distribution and metabolism in type I diabetics assessed by [123I]insulin scanning.
abstract: Scintigraphic scanning with [123I]insulin provides a direct and quantitative assessment of insulin uptake and disappearance at specific organ sites. Using this technique, the biodistribution and metabolism of insulin were studied in type 1 diabetic patients and normal subjects. The major organ of [123I]insulin uptake in both diabetic and normal subjects was the liver. After iv injection in normal subjects, the uptake of [123I]insulin by the liver was rapid, with peak activity at 7 min. Activity declined rapidly thereafter, consistent with rapid insulin degradation and clearance. Rapid uptake of [123I]insulin also occurred in the kidneys, although the uptake of insulin by the kidneys was about 80% of that by liver. In type 1 diabetic patients, uptake of [123I]insulin in these organ sites was lower than that in normal subjects; peak insulin uptakes in liver and kidneys were 21% and 40% lower than those in normal subjects, respectively. The kinetics of insulin clearance from the liver was comparable in diabetic and normal subjects, whereas clearance from the kidneys was decreased in diabetics. The plasma clearance of [123I]insulin was decreased in diabetic patients, as was insulin degradation, assessed by trichloroacetic acid precipitability. Thirty minutes after injection, 70.9 +/- 3.8% (+/- SEM) of [123I]insulin in the plasma of diabetics was trichloroacetic acid precipitable vs. only 53.9 +/- 4.0% in normal subjects. A positive correlation was present between the organ uptake of [123I]insulin in the liver or kidneys and insulin degradation (r = 0.74; P less than 0.001). Both decreased insulin uptake in the liver and kidneys and decreased insulin degradation were inversely correlated to the binding capacity of antiinsulin antibodies in plasma of diabetics (r = -0.87 to -0.92; P less than 0.001). In summary, type 1 diabetic patients have altered patterns of insulin biodistribution and metabolism, with decreased organ uptake and slow degradation of [123I]insulin, which correlated with the insulin antibody-binding capacity of their serum. Thus, antiinsulin antibodies, even at subclinical concentrations, may modulate the metabolic effects of insulin in the diabetic by prolonging the biological half-life of the hormone as well as by altering its distribution and uptake at specific organ sites.
mesh_terms: D000328:Adult; D000915:Antibody Affinity; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000276:immunology / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D007328:Insulin; D007457:Iodine Radioisotopes