Supramolecular insulin assembly II for a sustained treatment of type 1 diabetes mellitus

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 for...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-07, Vol.107 (30), p.13246-13251
Main Authors: Gupta, Sarika, Chattopadhyay, Tandrika, Singh, Mahendra Pal, Surolia, Avadhesha, Lennarz, William J.
Format: Article
Language:English
Subjects:
Adipocytes - cytology
Adipocytes - drug effects
Adipocytes - metabolism
Alloxan
Amyloid - chemistry
Amyloid - metabolism
Amyloid - ultrastructure
Amyloids
Animals
Biological Sciences
Blood Glucose - analysis
Cattle
Cells, Cultured
Congo Red - chemistry
Diabetes
Diabetes complications
Diabetes Mellitus, Experimental - blood
Diabetes Mellitus, Experimental - chemically induced
Diabetes Mellitus, Experimental - drug therapy
Diabetes Mellitus, Type 1 - blood
Diabetes Mellitus, Type 1 - drug therapy
Endocrinology
Glucose
Glucose Tolerance Test
Humans
Hypoglycemia
Hypoglycemic Agents - chemistry
Hypoglycemic Agents - therapeutic use
Insulin
Insulin - chemistry
Insulin - metabolism
Insulin - therapeutic use
Male
Medical treatment
Mice
Mice, Inbred C57BL
Microscopy, Atomic Force
Microscopy, Electron, Transmission
Molecular biology
Monomers
Protein Multimerization
Rabbits
Rats
Rats, Wistar
Spectroscopy, Fourier Transform Infrared
Streptozocin
Type 1 diabetes mellitus
Type 2 diabetes mellitus
Ungulates
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1005704107