Glutamate Receptors in Pancreatic Cells as a Pharmacological Target for Prevention of Hypoglycemia in Diabetes
Per-Olof Berggren, Alejandro Caicedo and Over Cabrera
Problem
Most cases of hypoglycemia seen in clinical practice are diabetics over-treated with insulin or sulfonylureas. Were it not for the devastating effects of hypoglycemia on the brain, diabetes would be easy to treat. Insulin excess causes glucose concentrations in the blood to fall to low levels in diabetic patients. In these patients however, glucagon secretion, in response to low glucose levels, is not stimulated as would be the case in people without diabetes.
Solution
The novel finding that these receptors are present in alpha cells of the human pancreas and that the cells retain their potential to secrete glucagon points to an alternative pathway and treatment approach in modulating glucose levels. Because hypoglycemia is the limiting factor in the management of diabetes, therapies that arise from this invention may improve the treatment of diabetes in millions of affected people. It might also reduce the likelihood of recurrent hypoglycemia with its attendant morbidity and potential mortality.
Competitive Advantage
In contrast to current approaches to treat hypoglycemia, this therapy enhances endogenous glucagon secretion and would prevent recurrent occurrences of hypoglycemia.
Applications
The application of drugs that positively modulate glutamate receptors in pancreatic alpha cells will increase their ability to efficiently secrete glucagon in response to hypoglycemia. We expect this treatment approach will reduce recurrent hypoglycemia associated with drug-treated diabetes.
Patent Status
International Patent Application No. PCT/US2009/037002 was filed on March 12, 2009.
Licensing Opportunity
We are seeking a commercialization partnership for improving the treatment of diabetes and preventing the recurrence of hypoglycemia.
About the Inventors
Per-Olof Berggren, Ph.D., is Professor and Head of Cell Biology and Signal Transduction at the Diabetes Research Institute (DRI). He holds a joint appointment as Professor and Head, Experimental Endocrinology at Karolinska Institutet in Stockholm, Sweden. His research interests are in Type 1 diabetes, Type 2 diabetes and signal-transduction in the endocrine pancreas.
Alejandro Caicedo, Ph.D., is Assistant Professor of Surgery in the Cell Biology and Signal Transduction laboratory at the DRI.
Over Cabrera, Ph.D., is Senior Research Associate at the DRI.
Selected References
Cabrera O, Jacques-Silva MC, Speier S, Yang S-N, Kohler M, Berman DM, Kenyon NS, Ricordi C, Caicedo A, Berggren P, Glutamate is a positive autocrine signal for glucagon release, Cell Metab. 2008 Jun;7(6):545-54.
