- A lab study in donated human pancreatic islets found that chronic exposure to glibenclamide (a sulphonylurea) reduced glucose responsive insulin release and increased beta cell stress and cell death
- The researchers report signs of loss of beta cell identity, meaning surviving cells looked less like healthy insulin producing cells over time
- Research could help explain why sulphonylureas often lose effectiveness with long term use
Sulphonylureas are among the older, widely used tablets for type 2 diabetes.
This class of drug works by pushing the pancreas to release more insulin.
They can be very effective at first – however many people find they do not last as well as newer options and they can come with a higher risk of hypos and weight gain.
A study published in Diabetes, Obesity and Metabolism has added a possible biological explanation for why their benefit can fade over time.
This was not a clinical trial in people. It was a laboratory study using human pancreatic islets from organ donors.
The team cultured the islets for 4 to 7 days under normal glucose conditions and compared islets exposed to glibenclamide (also known as glyburide) with islets not exposed to the drug.
Compared with control islets, the glibenclamide exposed islets showed:
- More insulin release at low glucose but worse glucose stimulated insulin secretion, meaning the cells responded less appropriately when glucose rose
- More cell stress in the endoplasmic reticulum, a part of the cell involved in handling proteins
- Higher levels of beta cell apoptosis (cell death)
- Lower expression of key genes and proteins linked to beta cell identity and insulin production
They also found that adding a chemical chaperone called 4 phenylbutyrate reduced ER stress and helped prevent some of the drop in key beta cell factors, suggesting ER stress is part of the pathway.
- Experimental insulin patch could replace injections
- New affordable insulin pen to be launched
- Plant-based eating may help some people with type 1 diabetes use less insulin
What does “loss of beta cell identity” mean in plain English?
In type 2 diabetes, beta cells can fail in two ways: they can die, or they can survive but become less able to behave like proper insulin producing cells.
This study suggests sulphonylureas may, over time, push beta cells towards that second problem as well as increasing cell stress and death.
That is one plausible reason for “secondary failure”, where sulphonylureas stop controlling glucose after a period of initial improvement.
