Researchers at ZymoGenetics, a wholly owned subsidiary ofNovo Nordisk A/S, reported in today's issue of Science thatthey have cloned the gene for the glucagon receptor.
"It's not just another receptor," author Gary Rosenberg toldBioWorld, "because it's important in diabetes, and everythingthat happens downstream from the receptor has been knownfor years. The receptor itself remained an enigma."
Glucagon causes the conversion of fat reserves and the releaseof glucose into the bloodstream, while insulin regulates theuptake of glucose by cells.
"We'll use the glucagon receptor to set up screens to look fororganic compounds that bind to it that may have a role intreating type II diabetes," said Chuck Gray, scientific affairsmanager of the 12-year-old Seattle research company.
Current treatments for type II, non-insulin dependent diabetesare not effective for long, he said. Novo Nordisk is a leadingsupplier of insulin to patients who rely on injections of thishormone to moderate their glucose metabolism.
Besides diabetes, ZymoGenetics focuses on protein therapeuticsfor wound healing, blood clotting, and coagulation andosteoporosis, Gray said, and has a second focus in medicinalchemistry.
The glucagon receptor, cloned from an expression cloninglibrary of rat liver cDNAs, has eluded researchers for yearsbecause it cannot be detected for purification after themembrane where it resides is disrupted, Rosenberg said. It is asmall, sticky peptide that cannot be easily kept in solution. "For10 or 15 years people tried to get their hands on it," he said. "Ithink most people just abandoned it."
Because type II diabetes is more widespread than type I, thereceptor's potential assistance in finding new treatments"represents a big opportunity," Gray added.
The researchers may examine the pancreas to see if a similarreceptor to the liver version is located there, where specializedcells also produce insulin.
The receptor belongs to a class of G-coupled, 7-transmembranedomain receptors, which are already well-characterized.However, its nature is not therapeutically important since thereis no evidence for aberrant forms in the disease.
-- Nancy Garcia Associate Editor
(c) 1997 American Health Consultants. All rights reserved.