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We have measured the turnover rate ofthe polypeptide subunits of the insulin receptor in cultured human lymphocytes (IM-9 line) and have investigated the mechanism of insulin-induced receptor loss. To estimate the rate of receptor degradation, lymphocytes were either pulse-labeled with [asSimethionine or surface labeled with NaF4 and lactoperoxidase. The insulin receptor was isolated by immunoprecipitation with anti-receptor antibody, and the rate of loss of radioactivity from each receptor subunit was determined after sodium dodecyl sulfate/polyacrylamide gel electrophoresis. Two major (Mr 135,000 and 95,000) and one minor (Mr 210,000) subunits were found. By both labeling methods, the half-lives of the major insulin receptor subunits were 9-12 hr in normal media. When the cells were cultured in media containing 1 FAM insulin the turnover was accelerated 2.5-to 3.5-fold (half-life approximately 3 hr). The increase in degradation rate was dependent on the insulin concentration and correlated well with the ability to "down-regulate" the receptor. Guinea pig insulin was about 2% as active as porcine insulin in accelerating degradation, and human growth hormone was without effect. The acceleration of receptor degradation induced by insulin was partially blocked by 100 pM cycloheximide. The rate of biosynthesis of the insulin receptor did not appear to be altered in the presence of 1 jpM insulin after correction for the change in degradation rate. In conclusion, these data demonstrate that insulin-induced receptor loss in cultured lymphocytes is due to accelerated receptor degradation. The ability of hormones to regulate the concentration of their receptors on the surface of cells ("down-regulation") is a fundamental mechanism for the regulation of target cell sensitivity (1). Lymphocytes cultured in media containing various concentrations of insulin exhibit a time-and concentration-dependent decrease in insulin receptor concentration (2). Similarly, the number of insulin receptors on cells in vivo in many diseases is inversely related to the concentration ofinsulin to which the cells are exposed (3). This mechanism of insulin-induced loss of its own receptor is thought to play a major role in the pathogenesis of insulin resistance in many disease states, including obesity (3,4).Using autoantibodies against the insulin receptor, we have recently identified the receptor subunits by specific immunoprecipitation of either externally or biosynthetically labeled proteins (5-7). In the present study we have used these techniques to measure directly the turnover rate ofinsulin receptor subunits and to study the mechanism of down-regulation of insulin receptors in human cultured lymphocytes. MATERIALS AND METHODSMaterials. Porcine insulin was purchased from Elanco (Indianapolis, IN); guinea pig insulin and human growth hormone were gifts from the Research Resources Program, and the National Pituitary Agency, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health.Na'"I, [a...

Objective: To quantify the treatment effects of interradicular miniscrew anchorage and to confirm the validity of the clinical usage of interradicular miniscrews in the distal movement of maxillary molars in nonextraction treatment. Materials and Methods: Twenty-four maxillary molars were moved to the distal using miniscrews placed in the interradicular space between the second premolar and the first molar at an oblique angle of 20 to 30 degrees to the long axis of the proximal tooth. The teeth were evaluated as to how the molars were moved to the distal with the use of lateral cephalograms and dental casts. Results: Maxillary molars were moved to the distal by 2.8 mm with distal tipping of 4.8 degrees and intruded by 0.6 mm. Maxillary incisors were moved to the distal by 2.7 mm with palatal tipping of 4.3 degrees. Molar extrusion and/or consequent mandibular rotation was not observed in any patient. Conclusion: Miniscrews placed in the maxillary interradicular space provide successful molar distal movement of 2.8 mm without patient compliance and with no undesirable side effects such as incisor proclination, clockwise mandibular rotation, or root resorption. (Angle Orthod. 2009;79: 78-84.)

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