| Diabetes is a pandemic affecting over 171 million people worldwide, and experts expect this number to double by 2030. It is a disease in which pancreatic beta cells do not produce, or the body becomes resistant to, insulin. Insulin injections have been used in the treatment of diabetes since 1922. Insulin is a protein that will not survive the digestive tract and thus therapy is an invasive treatment that requires the patient to be subjected to repeated injection. Here we show that a non-invasive oral delivery route can be achieved for insulin by utilizing the preexisting uptake pathway of vitamin B 12. We found in STZ-diabetic rat models that insulin conjugated to vitamin B12 has the capacity to lower blood glucose levels when administered orally. Investigations into the structure of this derivative and the nature of its interaction with the insulin receptor have also been carried out with molecular dynamics and immunoelectron microscopy. We anticipate our findings to be a significant step toward developing an orally active, non-invasive application for basal insulin therapy in type 1 diabetes. |
