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- Title
Induction of hyperinsulinemia combined with hyperglycemia and hypertriglyceridemia increases plasminogen activator inhibitor 1 in blood in normal human subjects.
- Authors
Calles-Escandon, Jorge; Mirza, Shirwan A.; Sobel, Burton E.; Schneider, David J.; Calles-Escandon, J; Mirza, S A; Sobel, B E; Schneider, D J
- Abstract
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 h in ten normal lean individuals (54 +/- 3 years) resulting in increased insulin (42 +/- 5 microU/dl), glucose (200 +/- 24 mg/dl), and triglycerides (425 +/- 45 mg/dl), simulating changes in type 2 diabetes. In contrast to results with infusion of saline alone (n = 16) and euglycemic-hyperinsulinemic clamps (n = 10, serum insulin = 89 +/- 7 microU/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 hyperinsulinemia, 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 well as achieving glycemic and lipidemic control in individuals with type 2 diabetes.
- Subjects
INSULIN shock; HYPERGLYCEMIA; HYPERTRIGLYCERIDEMIA
- Publication
Diabetes, 1998, Vol 47, Issue 2, p290
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diab.47.2.290