Item
#6
How
High-Dose Aspirin Improves Glucose Metabolism in Type 2
Salicylates
have recently been shown to ameliorate insulin resistance and improve
glucose tolerance in patients with type 2 diabetes.
Recent
studies have implicated fatty acid-dependent activation of the serine
kinase IKKbeta, which plays a key role in tissue inflammation, in the
pathogenesis of insulin resistance. High doses of salicylates have
recently been shown to inhibit IKKbeta activity and might therefore
ameliorate insulin resistance and improve glucose tolerance in
patients with type 2 diabetes.
To
rest this hypothesis, we studied nine type 2 diabetic subjects before
and after 2 weeks of treatment with aspirin (similar to7 g/d).
Subjects underwent mixed-meal tolerance tests and hyperinsulinemic-
euglycemic clamps with [6, 6-H-2(2)]glucose to assess glucose turnover
before and after treatment.
High-dose
aspirin treatment resulted in a similar to 25% reduction in fasting
plasma glucose, associated with a similar to15% reduction in total
cholesterol and C-reactive protein, a similar to 50% reduction in
triglycerides, and a similar to 30% reduction in insulin clearance,
despite no change in body weight. During a mixed-meal tolerance test,
the areas under the curve for plasma glucose and fatty acid levels
decreased by similar to 20% and similar to 50%, respectively. Aspirin
treatment also resulted in a similar to 20% reduction in basal rates
of hepatic glucose production and a similar to 20% improvement in
insulin-stimulated peripheral glucose uptake under matched plasma
insulin concentrations during the clamp. In conclusion, these data
support the hypothesis that IKKbeta represents a new target for
treating type 2 diabetes mellitus.
Journal of
Clinical Investigation, 2002 109/10
(1321-1326)
