INSULIN BINDING IN DIABETES - RELATIONSHIPS WITH PLASMA-INSULIN LEVELS AND INSULIN SENSITIVITY
INSULIN BINDING IN DIABETES - RELATIONSHIPS WITH PLASMA-INSULIN LEVELS AND INSULIN SENSITIVITY
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DOI：
10.2337/diab.26.7.680
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发表时间：
1977-01-01
期刊：
影响因子：
7.7
通讯作者：
REAVEN, GM
中科院分区：
文献类型：
--
作者：
OLEFSKY, JM;REAVEN, GM
研究了胰岛素与正常受试者和成人糖尿病患者分离的循环单核细胞的结合。糖尿病受试者为非酮症患者，其糖耐量不耐受程度从口服糖耐量异常（化学性糖尿病）到明显的空腹高血糖不等。化学性糖尿病患者胰岛素与单核细胞的结合减少了45%，这种减少是继发于每个细胞受体位点数量的减少（正常人每个单核细胞15000个位点，而化学性糖尿病患者每个单核细胞8500个位点）。当检查正常和化学性糖尿病受试者的个人数据时，发现胰岛素结合量与空腹血浆胰岛素水平（r = 0.61, P > 0.001）和口服葡萄糖耐量试验期间的胰岛素增量面积（r = 0.49, P > 0.001）之间存在高度显著的负相关。胰岛素结合与胰岛素抵抗程度呈负相关（r = 0.65, P < 0.001）。结合胰岛素的能力与血浆胰岛素水平和胰岛素敏感性呈负相关，胰岛素抵抗和高胰岛素血症的化学性糖尿病患者结合胰岛素的能力下降。许多空腹高血糖患者的胰岛素结合也降低。虽然作为一个群体，这些患者有空腹高胰岛素血症，他们是低胰岛素血症，以应对葡萄糖的挑战。将他们的数据与正常和化学性糖尿病患者的数据相结合，增强了胰岛素结合与空腹胰岛素水平之间的关系（r = 0.68, P < 0.001），但消除了胰岛素结合与胰岛素增量面积之间的关系。在这些受试者中，胰岛素结合与胰岛素抵抗程度之间没有发现显著的相关性（r = 0.19， N.S.[无统计学意义]），提示这些受试者的全部或大部分胰岛素抵抗与胰岛素受体的变化无关。如果将受试者作为一个群体，在化学性糖尿病患者和空腹高血糖的糖尿病患者中，胰岛素与单核细胞的结合减少。在成人非酮症糖尿病的整个谱系中，空腹高胰岛素血症患者的胰岛素结合减少到单核细胞，而胰岛素水平正常的受试者的胰岛素结合正常。化学性糖尿病患者的胰岛素抵抗可能与胰岛素受体的减少有关，但空腹高血糖患者的情况似乎并非如此。血浆胰岛素水平与胰岛素结合呈负相关，但与胰岛素受体变化相关的是基础水平，而不是刺激水平。
Insulin binding to isolated circulating monocytes from normal subjects and adult patients with diabetes was studied. The diabetic subjects were nonketotic, and their degree of glucose intolerance varied from an abnormal oral glucose tolerance test (chemical diabetes) to significant fasting hyperglycemia. Patients with chemical diabetes had a 45% decrease in insulin binding to monocytes, and this decrease was secondary to a reduction in the number of receptor sites per cell (normals, 15,000 sites per monocyte vs. 8500 sites per monocyte for chemical diabetics). When the individual data from the normal and chemical diabetic subjects were examined, a highly significant inverse correlation was found between the amount of insulin bound and both the fasting plasma insulin level (r = 0.61, P > 0.001) and the incremental insulin area during an oral glucose tolerance test (r = 0.49, P > 0.001). Insulin binding was closely and inversely correlated to the degree of insulin resistance (r = 0.65, P > 0.001) among these subjects. The ability to bind insulin is inversely related to both the plasma insulin level and insulin sensitivity, and chemical diabetics who are insulin-resistant and hyperinsulinemic have a decreased ability to bind insulin. Many patients with fasting hyperglycemia also have decreased insulin binding. Although as a group these patients have fasting hyperinsulinemia, they are hypoinsulinemic in response to a glucose challenge. Inclusion of their data with that of the normal and chemical-diabetic patients enhances the relationship between insulin binding and fasting insulin level (r = 0.68, P > 0.001) but obliterates the relationship between insulin binding and incremental insulin area. In these subjects no significant correlation was found between insulin binding and the degree of insulin resistance (r = 0.19, N.S. [nonsignificant]), suggesting that all or most of the insulin resistance in these subjects was independent of changes in insulin receptors. If the subjects are taken as a group, in patients with chemical diabetes and in diabetic patients with fasting hyperglycemia, insulin binding to monocytes is decreased. Over the entire spectrum of adult, nonketotic diabetes, insulin binding is decreased to monocytes from patients with fasting hyperinsulinemia, while subjects with normal insulin levels have normal insulin binding. The insulin resistance of patients with chemical diabetes may be related to a decrease in insulin receptors, but this does not appear to be the case for patients with fasting hyperglycemia. Plasma insulin levels are inversely related to insulin binding, but it is the basal, not the stimulated levels that are associated with changes in insulin receptors.