2. Academic Validation
  3. Dose Dependent Effect of Sulfamethoxazole on Inhibiting KATP Channel of Mouse Pancreatic β Cell

Dose Dependent Effect of Sulfamethoxazole on Inhibiting KATP Channel of Mouse Pancreatic β Cell

  • Dose Response. 2023 Sep 28;21(3):15593258231203611. doi: 10.1177/15593258231203611.
Hiroshi Ogata 1,  Shigeki Kitamura 1 2,  Makoto Fujiwara 1 3,  Masaru Shimizu 1 4,  Chengbo Tan 5,  Songji Zhao 5,  Yuko Maejima 1,  Kenju Shimomura 1
Affiliations

Affiliations

  • 1 Department of Bioregulation and Pharmacological Medicine, School of Medicine, Fukushima Medical University, Fukushima, Japan.
  • 2 Department of Plastic and Reconstructive Surgery, School of Medicine, Fukushima Medical University, Fukushima, Japan.
  • 3 Department of Diabetes, Endocrinology and Metabolism, Tsukuba Medical Center, Ibaragi, Japan.
  • 4 Department of Neurology, Matsumura General Hospital, Fukushima, Japan.
  • 5 Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, Fukushima, Japan.
PMID: 37780606 DOI: 10.1177/15593258231203611
Abstract

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 (KATP) channels and induces Insulin secretion. However, there are no detail reports that measure the effective dose that can close KATP channels and induce Insulin secretion. In this study, whole-cell patch clamp recording was utilized to measure the effect of SMX on KATP 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 KATP channel in pancreatic β cell membrane and induce Insulin secretion in relatively high concentration. The half maximal inhibitory concentration (IC50) for KATP channel activity of SMX was .46 ± .08 mM. It was also shown that a near IC50 concentration of SMX (.5 mM) was able to nearly fully block the KATP 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.

Keywords

KATP channel; hypoglycaemia; insulin secretion; sulfamethoxazole.

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