Promising Target for Diabetes Treatment Discovered by Scientists

Model of insulin inhibitory receptor ‘inceptor’ (in black) desensetizing the insulin recptor (in color) on a pancreatic beta cell. Insulin in blue.
Credit: Helmholtz Zentrum München

Researchers have discovered a novel and druggable insulin inhibitory receptor, named inceptor. The latest study from Helmholtz Zentrum Muenchen, the Technical University of Munich, and the German Center for Diabetes Research is a significant milestone for diabetes research as the scientific community celebrates 100 years of insulin and 50 years of insulin receptor discovery. The blocking of inceptor function leads to an increased sensitization of the insulin signaling pathway in pancreatic beta cells. This might allow protection and regeneration of beta cells for diabetes remission.

Diabetes mellitus is a complex disease characterized by the loss or dysfunction of insulin-producing beta cells in the islets of Langerhans, a specialist “micro-organ” in the pancreas that controls systemic blood sugar levels. Diabetes complications, such as chronic high blood sugar, systemic metabolic failure and, in the long-term, multi-organ damage, create enormous medical and social burdens and leads to premature death. Currently no pharmacological treatment can stop or reverse disease progression. Previous studies have demonstrated that intensive insulin therapy has the potential for improved blood sugar control and diabetes remission but also leads to unintended weight gain and even more severe side effects, such as an increased risk of deep drop in blood sugar causing unawareness.

Heiko Lickert’s research focuses on the development of regenerative approaches to treat diabetes complementary and alternative to the classical immunological and metabolic therapies. “Insulin resistance in pancreatic beta cells causes diabetes. Therapies that sensitize those cells to insulin may protect patients with diabetes against beta cell loss and failure,” says Lickert. With the discovery of the insulin inhibitory receptor, his research group has found a promising molecular target for beta cell protection and regeneration therapy that does not carry the unintended side effects of intensive insulin therapy.

In experiments with mice, the researchers showed that the function of inceptor is to shield the insulin-producing beta cells from constitutive insulin pathway activation. Remarkably, inceptor is upregulated in diabetes and by blocking insulin signaling it might contribute to insulin resistance.

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