Geffner M E, Bersch N, Nakamoto J M, Scott M, Johnson N B, Golde D W
Department of Pediatrics, University of California, Los Angeles, Medical Center 90024.
Diabetes. 1991 Jan;40(1):28-36. doi: 10.2337/diab.40.1.28.
Insulin resistance may be due directly to genetically programmed disorders of insulin action or acquired defects in which environmental factors influence insulin action. To address the issue of this distinction, we studied the ability of insulin to stimulate colony formation in primary cultures of erythroid progenitors (assumed to retain environmental influences) and immortalized T lymphocytes (presumed to reflect only genetic influences). Four patients with hyperinsulinemia and disturbed glucose metabolism were studied (2 patients with acanthosis nigricans, 1 of whom had circulating anti-insulin-receptor antibodies, 1 with partial lipodystrophy, and 1 with Cushing's syndrome). The mean colony-forming ability of their erythroid progenitor cells in response to insulin stimulation (less than or equal to 1.6 pM) was significantly blunted compared with control cells (P less than 0.05). The mean responsiveness of their immortalized T-lymphoblast cell lines to similar insulin concentrations was no different than that of control T-lymphocyte lines, consistent with an acquired cause for the observed insulin resistance in each case. A T-lymphocyte line from a patient with leprechaunism, however, showed no stimulation in response to physiological concentrations of insulin. With these same in vitro methodologies, there was normal T-lymphocyte line responsiveness to insulinlike growth factor I (IGF-I) or insulin concentrations greater than 8.6 pM; both of these responses could be completely blocked by preincubation with an antibody to the IGF-I receptor. These findings suggest that, despite resistance to physiological levels of insulin, the high circulating insulin concentrations present in the serum of these patients could mediate unwanted tissue-specific growth through an intact IGF-I receptor-effector mechanism.
胰岛素抵抗可能直接归因于胰岛素作用的基因程序性紊乱或后天性缺陷，其中环境因素会影响胰岛素作用。为了探讨这种区别，我们研究了胰岛素刺激红系祖细胞原代培养物（假定保留环境影响）和永生化T淋巴细胞（假定仅反映遗传影响）中集落形成的能力。研究了4例高胰岛素血症和糖代谢紊乱患者（2例黑棘皮病患者，其中1例有循环抗胰岛素受体抗体，1例部分脂肪营养不良，1例库欣综合征）。与对照细胞相比，他们的红系祖细胞对胰岛素刺激（小于或等于1.6 pM）的平均集落形成能力明显减弱（P小于0.05）。他们的永生化T淋巴细胞系对相似胰岛素浓度的平均反应性与对照T淋巴细胞系没有差异，这与每种情况下观察到的胰岛素抵抗的后天性原因一致。然而，来自一名妖精貌综合征患者的T淋巴细胞系对生理浓度的胰岛素没有刺激反应。使用相同的体外方法，T淋巴细胞系对胰岛素样生长因子I（IGF-I）或大于8.6 pM的胰岛素浓度有正常反应；这两种反应都可以通过与IGF-I受体抗体预孵育而完全阻断。这些发现表明，尽管对生理水平的胰岛素有抵抗，但这些患者血清中存在的高循环胰岛素浓度可通过完整的IGF-I受体-效应器机制介导不必要的组织特异性生长。
