Sulfonylureas May Inhibit K_ATP Channel Neuroprotection

Treatment with sulfonylureas may increase the risk of stroke mortality in patients with type 2 diabetes

FRIDAY, May 20, 2016 (HealthDay News) — Treatment with sulfonylureas (ATP-sensitive potassium [K_ATP] channel blockers) may inhibit the neuroprotective effects of K_ATP channel activation and increase the risk of stroke, according to an experimental study published online May 13 in Diabetes.

Rui Liu, from the University of Toronto, and colleagues examined the effect of sulfonylureas on K_ATP channels and whether they impact the outcomes of stroke in diabetes.

The researchers found that there was larger brain damage and poorer behavioral outcomes for streptozotocin-induced diabetic mice subjected to transient middle cerebral artery occlusion. Neuronal injury induced by oxygen-glucose deprivation (OGD) in vitro and permanent middle cerebral artery occlusion (pMCAO) in vivo was increased by blocking K_ATP channel by tolbutamide. The OGD and pMCAO effects were reduced by activating K_ATP channel by diazoxide. Early increases were seen in protein levels of N-methyl D-aspartate receptor 2B and postsynaptic density protein-9 in streptozotocin-induced diabetic mice; there was a subsequent decrease in phosphorylation of glycogen synthase kinase 3β. The odds ratio for stroke morbidity was increased in type 2 diabetes mellitus (T2DM) patients treated with sulfonylureas versus comparator drugs in systematic meta-analysis.

“These results suggest that sulfonylurea treatment in T2DM patients may inhibit neuroprotective effects of K_ATP channels and increase the risk of stroke,” the authors write.

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