Geffner M E, Golde D W
Department of Pediatrics, UCLA Medical Center.
Diabetes Care. 1988 Jun;11(6):500-5. doi: 10.2337/diacare.11.6.500.
States of hyperinsulinemia with resistance to insulin action on glucose disposal are frequently associated with proliferative tissue abnormalities of the skin (acanthosis nigricans), ovary, and heart. That insulin may be involved in the pathogenesis of these growth-related abnormalities despite resistance to its metabolic effects mediated through the insulin receptor is suggested by the known ability of high concentrations of insulin to stimulate DNA synthesis and cell proliferation in vitro through the insulin-like growth factor I (IGF-I) receptor. IGF-I receptors are present in skin keratinocytes, some ovarian tissue compartments, and in the heart. Furthermore, ovarian tissue from hyperinsulinemic insulin-resistant women responds to supraphysiologic insulin concentrations in vitro by enhanced steroidogenesis. Cultured, transformed T-lymphocytes from an infant with leprechaunism fail to augment basal-colony formation in response to physiologic insulin concentrations in vitro (compared to a doubling seen in normal subjects), but respond normally to supraphysiologic insulin concentrations, the effect of which is competitively inhibited by a monoclonal antibody to the IGF-I receptor. Thus, insulin action mediated through the IGF-I receptor may initiate growth-promoting tissue effects in the face of limited insulin effect on glucose metabolism. Such spillover actions may add to the morbidity associated with states of clinical insulin resistance.
胰岛素抵抗导致葡萄糖代谢异常的高胰岛素血症状态，常与皮肤（黑棘皮症）、卵巢和心脏的增殖性组织异常相关。尽管存在通过胰岛素受体介导的代谢作用抵抗，但高浓度胰岛素能够通过胰岛素样生长因子I（IGF-I）受体在体外刺激DNA合成和细胞增殖，这提示胰岛素可能参与了这些与生长相关异常的发病机制。IGF-I受体存在于皮肤角质形成细胞、部分卵巢组织区域以及心脏中。此外，高胰岛素血症胰岛素抵抗女性的卵巢组织在体外对超生理浓度的胰岛素有反应，表现为类固醇生成增加。一名患妖精貌综合征婴儿的培养转化T淋巴细胞，在体外对生理浓度胰岛素无反应（正常受试者可使集落形成增加一倍），但对超生理浓度胰岛素反应正常，且该作用可被抗IGF-I受体单克隆抗体竞争性抑制。因此，在胰岛素对葡萄糖代谢作用有限的情况下，通过IGF-I受体介导的胰岛素作用可能启动促进组织生长的效应。这种溢出作用可能会增加与临床胰岛素抵抗状态相关的发病率。
