Nutr Res Pract.  2014 Apr;8(2):146-150.

Naringenin stimulates cholecystokinin secretion in STC-1 cells

Affiliations
  • 1Division of Metabolism and Functionality Research, Korea Food Research Institute, 62 Road-1201 Anyang-Pangyo-Ro, Bundang, Sungnam, Gyeonggi 463-746, Korea. khyey@kfri.re.kr

Abstract

BACKGROUND/OBJECTIVES
Cholecystokinin (CCK), a hormone or neuropeptide, is secreted in response to intraluminal nutrients by enteroendocrine I-cells of the intestine and has important physiological actions related to appetite regulation and satiety. The stimulation on CCK secretion from the intestine is of potential relevance for body weight management. Naringenin (4',5,7-trihydroxyflavanone) and its glycoside naringin (naringenin 7-rhamnoglucoside) have been reported to have many biological functions. In the current study, we investigated the question of whether naringenin and naringin could stimulate CCK secretion and then examined the mechanisms involved in CCK release.
MATERIALS/METHODS
STC-1 cells were used as a model of enteroendocrine cells. CCK release and changes in intracellular Ca2+ ([Ca2+]i) were measured after incubation of cells with naringenin and naringin for 1 h.
RESULTS
Naringenin caused significant (P < 0.05) stimulation of CCK secretion, but naringin did not. In addition, regarding the secretory mechanisms, naringenin-induced CCK secretion involved increases in [Ca2+]i, influx of extracellular Ca2+, at least in part, and activation of TRP channels, including TRPA1.
CONCLUSION
Findings of this study suggest that naringenin could have a role in appetite regulation and satiety.

Keyword

Naringenin; cholecystokinin; TRPA1; enteroendocrine cells; appetite

MeSH Terms

Appetite
Appetite Regulation
Body Weight
Cholecystokinin*
Enteroendocrine Cells
Intestines
Neuropeptides
Cholecystokinin
Neuropeptides

Figure

  • Fig. 1 Effect of naringenin and naringin on CCK release in STC-1 cells. Naringenin and naringin were incubated in Hepes buffer with 1.2 mM Ca2+ at 37℃ for 60 min. AITC was used as a positive control. Values are expressed as mean ± SEM from three separate experiments performed in triplicate (n = 9). Bars not sharing the same letters differ significantly (P < 0.05) by Duncan's multiple range tests.

  • Fig. 2 Effect of naringenin and naringin on changes in [Ca2+]i. Cells were loaded with a calcium-indicator dye from the FLIPR Calcium 5 Assay Kit for 60 min. After placement of the cells into a Flex Station 3, naringenin and naringin were added at 20 sec. Values are expressed as mean ± SEM from three separate experiments performed in triplicate (n = 9). Bars not sharing the same letters differ significantly (P < 0.05) by Duncan's multiple range tests.

  • Fig. 3 Effect of extracelluar Ca2+-free conditions on naringenin-induced CCK release. Cells were exposed to naringenin in buffer containing 1.2 mM or 0 mM Ca2+ at 37℃ for 60 min. Values are expressed as mean ± SEM from three separate experiments performed in triplicate (n = 9). **P < 0.01, ***P < 0.001 vs. CCK release induced by naringenin in 1.2 mM Ca2+.

  • Fig. 4 Effect of extracelluar Ca2+-free conditions on naringenin-induced increases in [Ca2+]i. Cells were loaded with a calcium-indicator dye in the absence or presence of 1.25 mM Ca2+ for 60 min. Values are expressed as mean ± SEM from three separate experiments performed in triplicate (n = 9). ***P < 0.001 vs. [Ca2+]i increases induced by naringenin in 1.25 mM Ca2+.

  • Fig. 5 Effect of RR and HC-030031 on naringenin-induced CCK release. Cells were pre-incubated with 100 µM RR or 50 µM HC-030031 for 30 min before exposure to various concentrations of naringenin in Hepes buffer containing 1.2 mM Ca2+ at 37℃ for 60 min. Values are expressed as mean ± SEM from three separate experiments performed in triplicate (n = 9). *P < 0.05, **P < 0.01 vs. naringenin only.

  • Fig. 6 Effect of RR and HC-030031 on naringenin-induced increases in [Ca2+]i. Cells were loaded with a calcium-indicator dye in the absence or presence of 100 µM RR or 50 µM HC-030031 for 60 min. Values are expressed as mean ± SEM from three separate experiments performed in triplicate (n = 9). *P < 0.05, ***P < 0.001 vs. naringenin only.


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