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Insulin Degradation: Progress and Potential¹

Veterans Affairs Medical Center (W.C.D., R.G.B., F.G.H.), Omaha, Nebraska 68105; and Departments of Medicine (W.C.D., F.G.H.), Biochemistry and Molecular Biology (W.C.D., R.G.B.), and Pharmacology (F.G.H.), University of Nebraska Medical Center, Omaha, Nebraska 68193-3020

I. Introduction

II. Insulin Clearance

A. Liver

B. Kidney

C. Other tissues

D. Extracellular insulin degradation

III. Cellular Insulin Uptake

IV. Cellular Insulin Degradation

A. Degradation products

B. Assay for insulin degradation

C. Insulin-degrading enzymes

V. Biological Role of Insulin Degradation

VI. Insulin-IDE-Proteasome Interactions and Control of Protein Degradation

VII. Summary and Conclusions