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HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia.

Qiu HY, Yuan SS, Yang FY, Shi TT, Yang JK - J Diabetes Res (2015)

Bottom Line: The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents.In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice.Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China ; Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China.

ABSTRACT
The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 μmol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion.

No MeSH data available.


Related in: MedlinePlus

Glucose tolerance test in mice that received moxifloxacin or saline. (a and b) Blood glucose and serum insulin concentrations in wild-type mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. (c and d) Blood glucose and serum insulin concentrations in HERG knockout mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. ∗P < 0.05, ∗∗P < 0.01, n = 5.
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fig3: Glucose tolerance test in mice that received moxifloxacin or saline. (a and b) Blood glucose and serum insulin concentrations in wild-type mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. (c and d) Blood glucose and serum insulin concentrations in HERG knockout mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. ∗P < 0.05, ∗∗P < 0.01, n = 5.

Mentions: Blood glucose and insulin concentrations of mice that underwent the glucose tolerance test are shown in Figure 3. In wild-type mice, 200 mg/kg of moxifloxacin led to a reduction in the blood glucose concentration at 60 min (P = 0.0346) (Figure 3(a)). Insulin levels in the moxifloxacin group were higher than those in the saline group at 60 min (P = 0.0373) (Figure 3(b)). The areas under the blood glucose concentration versus time curve and the insulin concentration versus time curve differed (P = 0.0383  and 0.0383, resp.) (Figures 3(a) and 3(b)). There were no significant differences in blood glucose or insulin concentrations in HERG knockout mice treated with moxifloxacin or saline (Figures 3(c) and 3(d)).


HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia.

Qiu HY, Yuan SS, Yang FY, Shi TT, Yang JK - J Diabetes Res (2015)

Glucose tolerance test in mice that received moxifloxacin or saline. (a and b) Blood glucose and serum insulin concentrations in wild-type mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. (c and d) Blood glucose and serum insulin concentrations in HERG knockout mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. ∗P < 0.05, ∗∗P < 0.01, n = 5.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663361&req=5

fig3: Glucose tolerance test in mice that received moxifloxacin or saline. (a and b) Blood glucose and serum insulin concentrations in wild-type mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. (c and d) Blood glucose and serum insulin concentrations in HERG knockout mice that underwent a glucose tolerance test after treatment with 200 mg/kg of moxifloxacin or physiological saline. ∗P < 0.05, ∗∗P < 0.01, n = 5.
Mentions: Blood glucose and insulin concentrations of mice that underwent the glucose tolerance test are shown in Figure 3. In wild-type mice, 200 mg/kg of moxifloxacin led to a reduction in the blood glucose concentration at 60 min (P = 0.0346) (Figure 3(a)). Insulin levels in the moxifloxacin group were higher than those in the saline group at 60 min (P = 0.0373) (Figure 3(b)). The areas under the blood glucose concentration versus time curve and the insulin concentration versus time curve differed (P = 0.0383  and 0.0383, resp.) (Figures 3(a) and 3(b)). There were no significant differences in blood glucose or insulin concentrations in HERG knockout mice treated with moxifloxacin or saline (Figures 3(c) and 3(d)).

Bottom Line: The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents.In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice.Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China ; Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China.

ABSTRACT
The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 μmol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion.

No MeSH data available.


Related in: MedlinePlus