Regenerate Beta cells — prevent diabetes
Type 2 diabetes (T2D) is an autoimmune disease that develops after destruction of the insulin-producing pancreatic beta cells. The disease commences with insulin resistance, a stage where the body tries to compensate for its inability to use insulin effectively. This gradually leads to either a decrease in beta cell numbers or impaired insulin production. To shed light on the molecular mechanisms responsible for the impaired beta cell proliferation, the EU-funded BCELL-T2D project performed a time course analysis on a diabetic transgenic mouse model. The idea was to identify molecular targets that could be exploited therapeutically to regenerate the impaired beta cell mass. The different stages observed in human diabetes were recapitulated in the mouse model. At 4–9 weeks of age animals developed insulin resistance, frank diabetes was seen at 10–18 weeks of age, while advanced diabetes and its complications were observed only in animals over 19 weeks old. Interestingly, during the insulin resistance phase an increase in beta cell mass was observed. This proliferative expansion of beta cells coincided with an increase in cells expressing glucagon. Glucagon is a hormone that converts glycogen into glucose and stimulates the release of insulin. Mice expressing glucagon managed to compensate for insulin resistance and did not develop diabetes. Based on this interesting finding, BCELL-T2D researchers explored various approaches for inducing beta cell proliferation, including cell cycle inducers (cyclin C). Furthermore, through a library of small molecules, the coral-based compound epoxypukalide emerged as a candidate for supporting beta cell proliferation and function. Taken together, the outcomes of the BCELL-T2D study emphasised the potential of beta cell proliferation to revert the diabetic phenotype. Clinical validation of this approach may help prevent the onset of diabetes. Success would considerably reduce the healthcare burden associated with this disease and improve the quality of life of diabetic patients.
Keywords
Type 2 diabetes, mouse model, beta cell proliferation, epoxypukalide, insulin resistance
