Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P01275 (
glucagon
)
26,492
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated
glucagon-like peptide 1
(
GLP-1
) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated
GLP-1
release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of
GLP-1
levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-day gatifloxacin.
Gatifloxacin
-stimulated
GLP-1
release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K(ATP) channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated
GLP-1
without insulinotropic effect, effects of
GLP-1
and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2h) to
GLP-1
stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of
GLP-1
inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of
GLP-1
, in turn, high levels of
GLP-1
and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia.
...
PMID:Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats. 2320 Jul 76
