Osteoprotegerin Enhances Beta Cell Survival and Proliferation to Treat Diabetes

Beta cells, found in pancreatic islets, produce and secrete insulin and amylin. In patients with type I and type II diabetes, beta cell mass and function are diminished, leading to insufficient insulin secretion, hypoglycemia, and associated side effects that can be fatal, such as ketoacidosis, heart disease, stroke, kidney failure, amputation, and blindness. Treating diabetes with injections of supplementary insulin is often a financial and lifestyle burden on the patient.

Description

Osteoprotegerin (OPG), a soluble glycoprotein of the tumor necrosis factor superfamily and a key regulator in bone metabolism, has been identified as a potent enhancer of human beta cell proliferation and survival. Researchers have demonstrated that treatment with OPG can significantly ameliorate beta cell death and induce a significant increase in beta cells. OPG enhanced beta cell proliferation in young, aged, and diabetic mice alike, significantly delaying hyperglycemia in diabetic mice. OPG is one of the few known proteins with direct beneficial effects on human beta cells, and as such is a potential method to treat diabetic patients, metabolic syndrome, for ex vivo expansion of beta cells for transplant, and for in vitro expansion of beta cells derived from other sources.

Applications

· Treating diabetes and reducing the reliance on expensive insulin treatments

Advantages

· Reduces beta cell death
· Supports beta cell proliferation
· OPG is a downstream target of lactogens, which have been shown to protect beta cells against a variety of cell death inducers

Invention Readiness

In vivo data

IP Status

https://patents.google.com/patent/US9724386B2

Related Publication(s)

Kondegowda, N. G., Fenutria, R., Pollack, I. R., Orthofer, M., Garcia-Ocaña, A., Penninger, J. M., & Vasavada, R. C. (2015). Osteoprotegerin and Denosumab Stimulate Human Beta Cell Proliferation through Inhibition of the Receptor Activator of NF-κB Ligand Pathway. Cell Metabolism, 22(1), 77–85. https://doi.org/10.1016/j.cmet.2015.05.021