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 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.
Gupta
Sarika
S
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Chattopadhyay
Tandrika
T
Pal Singh
Mahendra
M
Surolia
Avadhesha
A
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000496:Alloxan; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002417:Cattle; D002478:Cells, Cultured; D003224:Congo Red / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000627:therapeutic use; D007328:Insulin / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D055503:Protein Multimerization; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013311:Streptozocin
D000682:Amyloid; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D003224:Congo Red; D013311:Streptozocin; D000496:Alloxan