Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 30, Pages 13246-13251Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1005704107
Keywords
protein folding; hyperglycemia; normoglycemia; insulin-like growth factor-1
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Diabetes is a chronic disease requiring continuous medical supervision and patient education to prevent acute secondary complications. In this study, we have harnessed the inherent property of insulin to aggregate into an oligomeric intermediate on the pathway to amyloid formation, to generate a form that exhibits controlled and sustained release for extended periods. Administration of a single dose of the insulin oligomer, defined here as the supramolecular insulin assembly II (SIA-II), to experimental animals rendered diabetic by streptozotocin or alloxan, released the hormone capable of maintaining physiologic glucose levels for > 120 days for bovine and > 140 days for recombinant human insulin without fasting hypoglycemia. Moreover, the novel SIA-II described here not only improved the glycemic control, but also reduced the extent of secondary diabetic complications.
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