Gatifloxacin affects GLUT1 gene expression and disturbs glucose homeostasis in vitro

Ge, Tian-Fang; Law, Pui Ying Peggy; Wong, Hau Yan; Ho, Yu‐Ling

doi:10.1016/j.ejphar.2007.07.038

Cited by 16 publications

(9 citation statements)

References 18 publications

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“…The target cDNAs were analyzed by real-time PCR with QuantiTest SYBR Green PCR kit (Takara) using ABI 7300 (Applied Biosystems, Foster City, CA) according to the protocols provided by the manufacturer. All primer sequences [24, 25] are presented in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Liver Plays a Major Role in FGF-21 Mediated Glucose Homeostasis

Liu

Cao

Hou

et al. 2018

Cell Physiol Biochem

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Background/Aims: The liver is a vital organ in vertebrates and has a wide range of functions, including glucose absorption, glycogen storage and glucose production. Fibroblast growth factor (FGF)-21 is a metabolic regulator that is primarily produced by the liver. In this paper, we studied the effect of FGF-21 on glucose metabolism in the liver. Methods: The glucose uptake of cells was detected by 2-Deoxy-d-[³H] glucose; the synergy between insulin and FGF-21 was evaluated. The mRNA expression of GLUT1-4, G6Pase and PEPCK was detected by real-time PCR. Glycogen synthesis was examined by the anthrone method. Blood samples to monitor glucose in db/db diabetic mice were obtained by tail snip. Glucose metabolism in the liver and adipose tissues was observed by fluorescence microscopy. Results: In this study, FGF-21 stimulated glucose uptake by liver cells in both a dose and time-dependent manner, and at the same time, FGF-21 specifically stimulated GLUT1 expression in the liver cells. Furthermore, FGF-21 demonstrated a synergistic effect with insulin on glucose absorption, which is in accordance with enhanced GLUT-1 and -4 expression. Treatment with FGF-21 increased glycogen storage in liver cells. Consistent with in vitro results, FGF-21 lowered the plasma glucose level and stimulated GLUT1 expression and glycogen synthesis in db/db diabetic mice. Simultaneously, FGF-21 inhibited the gene expression of G6Pase and PEPCK. Conclusion: Our results suggest that FGF-21 clears up plasma glucose by stimulating glucose absorption in the liver of diabetic animals and decreases glucose release from the liver by inhibiting gluconeogenesis. Overall, these data indicate that the liver is an important target organ of FGF-21 to regulate glucose metabolism.

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Section: Methodsmentioning

confidence: 99%

Liver Plays a Major Role in FGF-21 Mediated Glucose Homeostasis

Liu

Cao

Hou

et al. 2018

Cell Physiol Biochem

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“…Through the same pathway, fluoroquinolones could also trigger vacuolation of pancreatic b cells, so causing a reduction in insulin levels and hyperglycemia [94][95][96]. An inhibitory effect of fluoroquinolones toward the mRNA expression of glucose transporter type 1 (GLUT1) and the insulin biosynthesis has been described [97]. Accordingly, gatifloxacin, levofloxacin and ciprofloxacin have been shown in experimental models to decrease, in a dose-dependent manner, the cellular transport of glucose to 41, 28 and 21%, respectively [97,98].…”

Section: Discussionmentioning

confidence: 97%

“…An inhibitory effect of fluoroquinolones toward the mRNA expression of glucose transporter type 1 (GLUT1) and the insulin biosynthesis has been described [97]. Accordingly, gatifloxacin, levofloxacin and ciprofloxacin have been shown in experimental models to decrease, in a dose-dependent manner, the cellular transport of glucose to 41, 28 and 21%, respectively [97,98]. As reported for CV events, there are no clear explanations about the chemical structure of quinolone nucleus responsible for dysglycemia [9].…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular and metabolic safety profiles of the fluoroquinolones

Pugi

Bartoloni

et al. 2011

Expert Opinion on Drug Safety

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Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone. However, the benefit/risk profile of these agents could be stratified for the single compounds. Several predisposing factors, such as diabetes, heart illnesses and their related pharmacotherapies, might exacerbate the risk of potentially serious adverse events. In this context, the opportunity of the more appropriate choice among different fluoroquinolones could be applicable.

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“…Gatifloxacin 5, is a novel extended-spectrum fluoroquinolone (fourth-generation) with improved Gram-positive and anaerobe coverage compared with older agents such as ciprofloxacin 1 [9]. However, dysglycemia has been noted as the life-threatening adverse effect of gatifloxacin, which led to its withdrawal from the market in the United States in 2006 [10]. Thus, there exists continuous need for novel gatifloxacin derivatives, with better activity profile and tolerability, to overcome the limitations of gatifloxacin.…”

Section: Introductionmentioning

confidence: 98%