The research team from Washington University School of Medicine in St. Louis said that efficacy of drugs, sulfonylureas, used to treat type 2 diabetics substantially declines after several years of use, causing insulin secretion to shut down.
"Why this happens isn't clear yet, but we've found what may be cause for hope," said senior author Colin G. Nichols, Ph.D., the Carl F. Cori Professor and professor of cell biology and physiology.
"We've shown in a mouse model that whatever causes this shutdown doesn't kill the insulin-making beta cells of the pancreas or stop them from making insulin. Instead, it somehow stops them from secreting insulin," he said.
When they stopped receiving the drug, beta cells began secreting insulin again hours later, added Nichols.
"I find these experimental observations very exciting," said Alan Permutt, M.D., professor of medicine and of cell biology and physiology.
"But I'm very cautious that patients understand that the relevance of this model to human diabetes and its treatment still needs to be tested," he added.
Nichols said that if human beta cells also survive and could continue to produce insulin after long-term sulfonylurea exposure, it might be possible to rethink treatment strategies.
"Doctors now prescribe new long-acting sulfonylureas to establish a chronic presence of the drug in the bloodstream," he said.
"But it may be beneficial to use the older drugs that go away more quickly, allowing the beta cells time to recover," he added.
Nichols said that alternating periods of drug treatment with periods when the patient's symptoms are managed by insulin injection might help in treating the condition.
The researchers tested long-term failure of sulfonylureas with the availability of an implantable time-release capsule form of one of the drugs, glibenclamide.
They implanted the capsules in the necks of mice. The drugs initially caused mouse beta cells to release more insulin and blood sugar levels dropped rapidly.
Within a few days, though, the response to the drug reversed: Insulin secretion levels dropped, and blood sugar levels rose dramatically.
Examination of the pancreas showed that the animals' beta cells were still alive and contained normal levels of insulin.
The findings appear in Public Library of Science Medicine.