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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 2 847-851
Copyright © 2004 by The Endocrine Society

Insulin-Degrading Activity in Wound Fluid

William C. Duckworth, Janet Fawcett, Sreedevi Reddy and Jeffrey C. Page

Carl T. Hayden Veterans Affairs Medical Center, Phoenix, Arizona 85012

Address all correspondence and requests for reprints to: William C. Duckworth, M.D., Carl T. Hayden Veterans Affairs Medical Center (CS111E), 650 East Indian School Road, Phoenix, Arizona 85012

Patients with diabetes are at great risk of developing lower extremity ulcers. The management of diabetic foot ulcers typically includes early recognition and appropriate clinical care. Recent advances in wound treatment include topical growth factor therapy, which has been successful in diabetic wounds. Growth factors are decreased in wound fluid; this may be due to decreased supply, increased binding, or increased degradation of the naturally occurring growth factors. This study investigates the activity of the insulin-degrading enzyme in wound fluid. Wound fluid was obtained from patients with (n = 17) and without (n = 4) diabetes. Insulin degradation was assayed by incubating [125I]insulin with wound fluid and precipitation in trichloroacetic acid. Fluid from nondiabetics degraded 2.22 ± 0.73%, whereas diabetic fluid degraded significantly more (6.13 ± 1.48%; P < 0.05). In patients with diabetes, the degradation of insulin by wound fluid correlated with glucose control (hemoglobin A1c; r2 = 0.5353; P < 0.001), and patients with worse outcomes (i.e. amputation) had higher wound fluid insulin degradation. The biochemical characteristics of insulin degradation in the wound fluid were consistent with the characteristics of insulin-degrading enzyme. These data suggest that glucose control is a critical factor in wound healing, but a reduction in the insulin-degrading activity in the wound fluid is also a potential therapeutic target.

This work was supported in part by a Veterans Affairs Merit Review (to W.C.D.).

Abbreviations: HbA1c, Hemoglobin A1c; IDE, insulin-degrading enzyme; NEM, N-ethylmaleimide; PDGF, platelet-derived growth factor; TCA, trichloroacetic acid; V.A.C., Vacuum-Assisted Closure.




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S. M. Bauer, R. J. Bauer, and O. C. Velazquez
Angiogenesis, Vasculogenesis, and Induction of Healing in Chronic Wounds
Vascular and Endovascular Surgery, July 1, 2005; 39(4): 293 - 306.
[Abstract] [PDF]




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Copyright © 2004 by The Endocrine Society