Hjøllund E, Pedersen O, Richelsen B, Beck-Nielsen H, Sørensen N S
J Clin Invest. 1985 Dec;76(6):2091-6. doi: 10.1172/JCI112213.
Previous studies have shown cellular insulin resistance in conventionally treated insulin-dependent diabetics. To determine whether insulin resistance is also present in insulin-dependent diabetics before the commencement of insulin therapy, we studied nine newly diagnosed untreated insulin-dependent diabetics and nine control subjects. Insulin binding to adipocytes, monocytes, and erythrocytes was normal in the diabetic individuals. Basal (noninsulin stimulated) glucose transport rate was normal, whereas the maximal insulin responsiveness of glucose transport was severely impaired (P less than 0.02). Insulin sensitivity as judged by left or rightward shifts in the insulin dose-response curves was unchanged. Moreover, the basal lipogenesis rate measured at a glucose concentration of 0.5 mmol/liter was decreased in the diabetics (P less than 0.05), and the maximal insulin responsiveness of lipogenesis was also reduced (P less than 0.05). We conclude that fat cells from untreated insulin-deficient diabetics are insulin resistant. The major defects are (1) reduced maximal insulin responsiveness of glucose transport and conversion to lipids that are postbinding abnormalities, and (2) reduced basal glucose conversion to lipids.
以往的研究表明,接受常规治疗的胰岛素依赖型糖尿病患者存在细胞胰岛素抵抗。为了确定在开始胰岛素治疗之前胰岛素依赖型糖尿病患者是否也存在胰岛素抵抗,我们研究了9名新诊断的未经治疗的胰岛素依赖型糖尿病患者和9名对照受试者。糖尿病个体中胰岛素与脂肪细胞、单核细胞和红细胞的结合正常。基础(非胰岛素刺激)葡萄糖转运率正常,而葡萄糖转运的最大胰岛素反应性严重受损(P<0.02)。根据胰岛素剂量反应曲线的左移或右移判断的胰岛素敏感性未改变。此外,在葡萄糖浓度为0.5 mmol/升时测量的基础脂肪生成率在糖尿病患者中降低(P<0.05),脂肪生成的最大胰岛素反应性也降低(P<0.05)。我们得出结论,未经治疗的胰岛素缺乏型糖尿病患者的脂肪细胞存在胰岛素抵抗。主要缺陷是:(1)葡萄糖转运和转化为脂质的最大胰岛素反应性降低,这是结合后异常,以及(2)基础葡萄糖转化为脂质减少。