In a set of mouse experiments, scientists attempt to learn more about why sulfonylureas eventually fail in the treatment of patients with type 2 diabetes, as reported in an article released on October 27, 2008 in the open-access journal PLoS Medicine.

Type 2 diabetes is often treated using sulfonylurea drugs such as glibencalmide. These medications inhibit the ATP-driven potassium channels in pancreatic beta cells, pushing calcium to enter the beta cells, inducing them to release insulin in a process known as depolarization. This insulin causes blood glucose levels to fall temporarily, but long-term treatment with these types of medications eventually fails through an unknown mechanism.

To investigate this mechanism, Maria Remedi and Colin Nichols from the Washington University School of Medicine examined the pancreatic beta cells in mice treated with sulfonylureas. In their results, they displayed that the treatment does not cause death of pancreatic beta cells, but rather causes them to become permanently depolarized across the cell’s channels. They additionally showed that, after being treated by slow-release sulfonylureas, this beta cell failure is actually reversible if the treatment is removed.

If applicable to the human model, these findings have strong implications for sulfonylurea dosing. For instance, further investigation should be made into the use of low-dose or pulsed dose treatments, which could help prevent treatment failure. This evaluation should first be more fully evaluated in animals before it reaches any clinical stages.

Erik Renstrom and colleagues from Lund University contributed an accompanying perspective in which they discuss the implications of this study.

Chronic antidiabetic sulfonylureas in vivo: Reversible effects on mouse pancreatic b-cells.
Remedi MS, Nichols CG
PLoS Med 5(10):e206.
doi:10.1371/journal.pmed.0050206
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Why treatment fails in type 2 diabetes.
Rosengren A, Jing X, Eliasson L, Renström E
PLoS Med 5(10): e215.
doi:10.1371/journal.pmed.0050215
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Written by Anna Sophia McKenney