Limits...
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

HERG channel proteins expressed in human pancreatic islets. (a) Cell nuclei were stained with DAPI and are illustrated in blue. (b) Insulin immunoreactive cells (red) in the same islet. (c) HERG protein-positive cells (green) in the same islet. (d) Colocalization of insulin and HERG protein.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4663361&req=5

fig1: HERG channel proteins expressed in human pancreatic islets. (a) Cell nuclei were stained with DAPI and are illustrated in blue. (b) Insulin immunoreactive cells (red) in the same islet. (c) HERG protein-positive cells (green) in the same islet. (d) Colocalization of insulin and HERG protein.

Mentions: Pancreatic β-cells, which are located in pancreatic islets, were visualized by insulin immunoreactivity (Figure 1(b)). HERG protein-positive cells were located in these islets (Figure 1(c)). Colocalization of insulin and HERG by immunostaining indicated that HERG is expressed in pancreatic β-cells (Figure 1(d)).


HERG Protein Plays a Role in Moxifloxacin-Induced Hypoglycemia.

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

HERG channel proteins expressed in human pancreatic islets. (a) Cell nuclei were stained with DAPI and are illustrated in blue. (b) Insulin immunoreactive cells (red) in the same islet. (c) HERG protein-positive cells (green) in the same islet. (d) Colocalization of insulin and HERG protein.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: HERG channel proteins expressed in human pancreatic islets. (a) Cell nuclei were stained with DAPI and are illustrated in blue. (b) Insulin immunoreactive cells (red) in the same islet. (c) HERG protein-positive cells (green) in the same islet. (d) Colocalization of insulin and HERG protein.
Mentions: Pancreatic β-cells, which are located in pancreatic islets, were visualized by insulin immunoreactivity (Figure 1(b)). HERG protein-positive cells were located in these islets (Figure 1(c)). Colocalization of insulin and HERG by immunostaining indicated that HERG is expressed in pancreatic β-cells (Figure 1(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