National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
Proc Natl Acad Sci U S A. 2010 Jul 27;107(30):13246-51. doi: 10.1073/pnas.1005704107. Epub 2010 Jul 13.
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.
糖尿病是一种慢性病，需要持续的医疗监督和患者教育，以预防急性继发性并发症。在这项研究中，我们利用胰岛素的固有性质，使其在形成淀粉样纤维的途径中聚集成为低聚物中间体，从而产生一种具有可控和持续释放特性的形式，可以延长释放时间。向链脲佐菌素或阿霉素诱导的糖尿病实验动物单次给予胰岛素低聚物（这里定义为超分子胰岛素组装 II [SIA-II]），可以释放出能够维持生理葡萄糖水平的激素，牛胰岛素的半衰期超过 120 天，重组人胰岛素的半衰期超过 140 天，且不会出现空腹低血糖。此外，这里描述的新型 SIA-II 不仅改善了血糖控制，还降低了继发性糖尿病并发症的程度。
