Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia increases plasminogen activator inhibitor 1 in blood in normal human subjects
Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia increases plasminogen activator inhibitor 1 in blood in normal human subjects
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DOI：
10.2337/diabetes.47.2.290
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发表时间：
1998-02-01
期刊：
影响因子：
7.7
通讯作者：
Schneider, DJ
中科院分区：
文献类型：
--
作者：
Calles-Escandon, J;Mirza, SA;Schneider, DJ
纤溶酶原激活物抑制剂 1 (PAI-1) 增加引起的纤溶低下与 2 型糖尿病的血管病变有关，典型表现为胰岛素、葡萄糖和甘油三酯增加。然而，短期输注胰岛素并没有增加正常受试者的 PAI-1。我们假设诱导胰岛素增加伴随着葡萄糖和甘油三酯的增加会相应地增加 PAI-1；对 10 名正常瘦人（54 +/- 3 岁）进行 6 次输注 30% 葡萄糖和 10% 脂肪乳，导致胰岛素（42 +/- 5 mu U/dl）、葡萄糖（200 +/- 24 mg/dl）和甘油三酯（425 +/- 45 mg/dl）增加，模拟类型变化！ 2 型糖尿病，hn 与仅输注盐水 Cn = 16）和正常血糖高胰岛素钳夹（n = 10，血清胰岛素 = 89 +/- 7 mu U/dl）的结果相比，输注开始后 6 小时血液中的 PAI-1 显着增加（15 +/- 5 ng/ml，P < 0.05 与基线 = 7.4 +/- 1.1，盐水 6 h = 3.4 +/- 1.1，单独胰岛素 6 小时 = 3.7 +/- 0.8），并在另外 6 小时内保持升高（联合输注 = 13.8 +/- 3.8 ng/ml，盐水 = 6.7 +/- 2 ng/ml，单独胰岛素 = 7.8 +/- 1.7 ng/ml，P = 0.06），我们的数据表明，联合高胰岛素血症，高甘油三酯血症和高血糖可能通过增加血液中 PAI-1 水平而导致 2 型糖尿病纤溶低下。此外，这些结果强调了改变胰岛素抵抗以及实现 2 型糖尿病患者血糖和血脂控制的潜在重要性。
Hypofibrinolysis caused by increased plasminogen activator inhibitor 1 (PAI-1) has been implicated in the vasculopathy of type 2 diabetes, typified by increased insulin, glucose, and triglycerides. However, short-term infusions of insulin have not increased PAI-1 in normal subjects. We hypothesized that induction of increased insulin accompanied by increased glucose and triglycerides would increase PAI-1, accordingly; 30% glucose and 10% Intralipid were infused for 6 it int ten normal lean individuals (54 +/- 3 years) resulting in increased insulin (42 +/- 5 mu U/dl), glucose (200 +/- 24 mg/dl), and triglycerides (425 +/- 45 mg/dl), simulating changes in type! 2 diabetes, hn contrast to results with infusion of saline alone Cn = 16) and euglycemic-hyperinsulinemic clamps (n = 10, serum insulin = 89 +/- 7 mu U/dl), PAI-1 in blood increased significantly 6 h after the onset of infusion (15 +/- 5 ng/ml, P < 0.05 vs. baseline = 7.4 +/- 1.1, saline 6 h = 3.4 +/- 1.1, and insulin alone 6 h = 3.7 +/- 0.8) and remained elevated for an additional 6 h (combined infusion = 13.8 +/- 3.8 ng/ml, saline = 6.7 +/- 2 ng/ml, insulin alone = 7.8 +/- 1.7 ng/ml, P = 0.06), Our data suggest that combined hyperinsulemia, hypertriglyceridemia, and hyperglycemia are likely to contribute to hypofibrinolysis of type 2 diabetes by increasing the blood levels of PAI-1, Moreover, these results underscore the potential importance of modifying insulin resistance as n ell as achieving glycemic and lipidemic control in individuals with type 2 diabetes.