Koffler M, Raskin P, Womble D, Helderman J H
Renal Division, University of Texas Southwestern Medical Center, Dallas.
Diabetes. 1991 Mar;40(3):364-70. doi: 10.2337/diab.40.3.364.
Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 +/- 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 +/- 4 at time 0 to 2 +/- 2% sp Cr release (P less than 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence.(ABSTRACT TRUNCATED AT 250 WORDS)
体内胰岛素的急性调控可调节同种异体抗原呈递后活化T淋巴细胞上诱导的胰岛素受体的表达。本研究探讨了在健康正常个体和肥胖受试者的高胰岛素-正常血糖钳夹过程中，通过急性调控胰岛素来调节胰岛素受体表达所产生的免疫生物学后果。在高胰岛素血症的0、1和4小时，从7名正常志愿者和7名肥胖个体中分离出T淋巴细胞，并研究其1）在细胞膜上合成胰岛素受体的能力，2）在混合淋巴细胞培养中对同种异体抗原的反应（一种与完全培养基中胰岛素浓度的调控无关的免疫活性），以及3）对淋巴细胞介导的细胞毒性反应的反应（一种已知受胰岛素调节的免疫活性）。在正常个体中，受体数量降至基线的25%时，混合淋巴细胞培养中的同种异体反应性未受影响（高胰岛素血症4小时后为0小时时的95±9%），而淋巴细胞介导的细胞毒性从0小时时的14±4降至2±2%的特异性肌酐释放（P<0.02）。通过钳夹在7名肥胖受试者中实现的高胰岛素血症在同种异体抗原呈递后并未改变细胞膜上胰岛素受体的合成。在胰岛素受体膜表达没有进一步降低的情况下，混合淋巴细胞培养和淋巴细胞介导的细胞毒性反应均未受影响。得出的结论是，淋巴细胞中那些可被胰岛素调节的免疫活性受活化淋巴细胞上胰岛素受体表达调控的影响。因此，受体调控并非无效，而是具有重要的免疫生物学后果。（摘要截短于250字）
