Novel therapeutic interventions for management of diabetes

Diabetes is a chronic disease requiring continuous medical supervision and patient education to prevent acute secondary complications. For Type I Diabetes, current advocacy of intensive insulin therapy regimens involving multiple daily subcutaneous injections places a heavy burden of compliance on patients and has prompted interest in developing alternative, less invasive routes of delivery. Long acting insulin analogues, such as Glargine and Detemir achieve more constant glucose levels but suffered a setback due to induction of fasting hypoglycaemia. Thus the need for a suitable therapy, with the potential of improving the quality of patient life, still remains. In an attempt to address the issue of multiple injections and patient compliance, 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 as the supramolecular insulin assembly II (SIA-II), was capable of maintaining physiologic glucose levels in experimental diabetic animals without fasting hypoglycemia. Moreover, SIA-II not only improved the glycemic control, but also reduced the extent of secondary diabetic complications.
In case of Type II Diabetes, pharmacotherapy usually begins with oral agents such as sulfonylureas and thiazolidinediones, with multiple daily insulin injections being the last resort. As a novel interventional therapy utilizing endogenous cellular pathways, we found that BMP-7, a Bone Morphogenetic Protein, was able to augment glucose uptake in insulin sensitive tissues, by increasing Glut4 translocation, thereby aiding in lowering of blood glucose levels, and thus could function as an adjunct therapy and decrease hyperglycemia. This study delineates a novel and direct role of BMP signaling in the regulation of glucose homeostasis and insulin resistance. Improved metabolic parameters and restoration of glucose uptake upon BMP-7 administration to diabetic animals provides a new avenue for the treatment of metabolic syndrome.