The prevalence of type 2 diabetes is growing in the United States and around the world. The disease afflicts an estimated 504 million individuals globally, including 20.9 million Americans. Because of its characteristic insulin resistance, type 2 diabetes not only leads to short-term problems with glucose uptake, but it can also lead to long-term complications including other metabolic problems, cardiovascular disease, renal disease, loss of lower limb circulation/mobility, visual impairment, and eventually death. One culprit behind type 2 diabetes is the body’s reduced responsiveness to a hormone called glucagon-like peptide-1 (GLP-1), which normally stimulates insulin secretion. While GLP-1 treatment improves insulin secretion in studies of patients with type 2 diabetes, the short half-life of the active form of the hormone (less than 2 minutes) indicates that it is degraded rapidly, requiring continuous administration of high concentrations over the course of hours. To avoid the impracticalities of this strategy, a treatment that mimics the effects of the active form of GLP-1 but that remains intact longer would be highly desirable.
A metabolized variant of GLP-1 fused with an immunoglobulin increases insulin secretion and has cardiovascular protective effects
Recent research demonstrates that a breakdown product of the active form of GLP-1 holds promise as a potential treatment for type 2 diabetes. Because the product, which was originally thought to be an inactive form of GLP-1, is already broken down, it is less susceptible to degradation. It therefore lasts longer than the “active” form. When fused to an immunoglobulin, this GLP-1 variant is a potent stimulator of glucose-dependent insulin secretion in humans. Transgenic expression of this GLP-1/immunoglobulin fusion protein in mice increases serum insulin and enhances responsiveness to both glucose and insulin. As an added benefit, studies of the GLP-1 breakdown product have also shown cardiovascular protective effects in mouse models of either cardiac hypertrophy or myocardial infarction. Together, these data support the GLP-1/immunoglobulin fusion protein as a powerful potential treatment for both type 2 diabetes and cardiovascular disease.
- Treatment for type 2 diabetes
- Treatment for cardiovascular disease