Sinha M K, Taylor L G, Pories W J, Flickinger E G, Meelheim D, Atkinson S, Sehgal N S, Caro J F
Department of Medicine, School of Medicine, East Carolina University, Greenville, North Carolina 27834-4354.
J Clin Invest. 1987 Oct;80(4):1073-81. doi: 10.1172/JCI113163.
We have tested the hypothesis that in vitro exposure of insulin-resistant adipocytes with insulin results in improved insulin action. A primary culture system of adipocytes from obese subjects with or without non-insulin-dependent diabetes mellitus (NIDDM) and nonobese control subjects has been developed. The adipocytes when cultured in serum-free medium do not lose their original characteristics in regard to insulin binding and glucose transport. The adipocytes from three groups were incubated with insulin (0, 10(-10) M, and 10(-7) M) for 24 h at 37 degrees C, receptor-bound insulin was dissociated, and basal and insulin (1 X 10(-11)-10(-7) M)-stimulated glucose transport and 125I-insulin binding were determined. The 24-h insulin exposure of adipocytes from control subjects decreased basal and insulin-stimulated glucose transport. The effects of 1 X 10(-7) M insulin were more pronounced than 1 X 10(-10) M insulin. Similarly, insulin exposure decreased insulin sensitivity and responsiveness of cultured adipocytes from obese and NIDDM patients. The insulin-induced reduction in insulin sensitivity and responsiveness for glucose transport in three groups were due to alterations at insulin binding and postbinding levels. In conclusion, insulin induces insulin resistance in control adipocytes and further worsens the insulin resistance of adipocytes from obese and NIDDM subjects. For insulin to improve the insulin resistance of adipocytes from NIDDM patients, either more prolonged in vitro insulin exposure and/or other hormonal factors might be required.
胰岛素抵抗的脂肪细胞在体外与胰岛素接触会使胰岛素作用得到改善。我们建立了来自患有或未患有非胰岛素依赖型糖尿病（NIDDM）的肥胖受试者以及非肥胖对照受试者的脂肪细胞原代培养系统。当在无血清培养基中培养时，脂肪细胞在胰岛素结合和葡萄糖转运方面不会丧失其原始特性。将三组脂肪细胞在37℃下与胰岛素（0、10⁻¹⁰ M和10⁻⁷ M）孵育24小时，解离受体结合的胰岛素，并测定基础及胰岛素（1×10⁻¹¹ - 10⁻⁷ M）刺激的葡萄糖转运以及¹²⁵I胰岛素结合。对照受试者的脂肪细胞经24小时胰岛素暴露后，基础及胰岛素刺激的葡萄糖转运均降低。1×10⁻⁷ M胰岛素的作用比1×10⁻¹⁰ M胰岛素更明显。同样，胰岛素暴露降低了肥胖和NIDDM患者培养的脂肪细胞的胰岛素敏感性和反应性。三组中胰岛素诱导的葡萄糖转运胰岛素敏感性和反应性降低是由于胰岛素结合及结合后水平的改变。总之，胰岛素在对照脂肪细胞中诱导胰岛素抵抗，并使肥胖和NIDDM受试者的脂肪细胞的胰岛素抵抗进一步恶化。要使胰岛素改善NIDDM患者脂肪细胞的胰岛素抵抗，可能需要更长时间的体外胰岛素暴露和/或其他激素因素。
