Dose Dependent Effect of Sulfamethoxazole on Inhibiting K ATP Channel of Mouse Pancreatic β Cell.

Dose-response : a publication of International Hormesis Society(2023)

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摘要
Sulfamethoxazole (SMX) is widely used as an antibiotic in the clinical application with side effects of hypoglycemia. This is because SMX contains the sulfonamide structure, which closes ATP-sensitive potassium (K) channels and induces insulin secretion. However, there are no detail reports that measure the effective dose that can close K channels and induce insulin secretion. In this study, whole-cell patch clamp recording was utilized to measure the effect of SMX on K channel activity on pancreatic β cells. Also, the static incubation assay with mice islets was assessed to measure the insulin secretion capacity of SMX. SMX was shown to inhibit the K channel in pancreatic β cell membrane and induce insulin secretion in relatively high concentration. The half maximal inhibitory concentration (IC) for K channel activity of SMX was .46 ± .08 mM. It was also shown that a near IC concentration of SMX (.5 mM) was able to nearly fully block the K channel when simultaneously applied with low concentration sulfonylurea, tolbutamide (.01 mM). Our present data provide important information for the clinical use of SMX to treat infection in diabetic patients using sulfonylureas.
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