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Inhibitory effect of fructo‐oligosaccharides on inflammation‐associated apoptosis in GLP‐1 secreting L cells via inhibition of iNOS and cleaved caspase‐3 expression
Author(s) -
Wongkrasant Preedajit,
Muanprasat Chatchai
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00287
Subject(s) - inflammation , apoptosis , tumor necrosis factor alpha , secretion , glucagon like peptide 1 , pharmacology , cancer research , biology , medicine , endocrinology , diabetes mellitus , type 2 diabetes , biochemistry
Glucagon‐like peptide 1 (GLP‐1) released from enteroendocrine L‐cells regulate insulin secretion. Intestinal inflammation and GLP‐1 secretion impairment are the dominant phenotype in type 2 diabetes mellitus (T2DM) patients. Fructo‐oligosaccharides (FOS) is a prebiotic known to be associated with GLP‐1 release and glucose homeostasis. This study aimed to investigate effect of FOS on inflammation‐associated GLP‐1 unresponsiveness. Herein, using cell death assays, immunofluorescence staining, real time PCR and western blot analyses, we demonstrated that FOS suppressed the effect of tumor necrosis factor‐α (TNF‐α), a key pathogenic cytokine in T2DM, on L‐cells apoptosis. Interestingly, FOS did not suppress TNF‐α‐induced NF‐κB nuclear translocation, but inhibited expression of IL‐6, IL‐1β and TNF‐α mRNA levels and iNOS and cleaved caspase‐3. Of particular importance, GLP‐1 secretion assay revealed that FOS rescued TNF‐α‐mediated GLP‐1 unresponsiveness in L cells. In conclusion, our study demonstrated the beneficial effects of FOS in maintaining GLP‐1 level and its mechanistic insights. Therefore, FOS exerts a novel class of drug candidate for the treatment of T2DM, at least in part, by targeting GLP‐1 signaling. Support or Funding Information This work is supported by the Thailand Research Fund (DBG6180029), Faculty of Science Mahidol University and Faculty of Medicine Ramathibodi Hospital Mahidol University. Financial support from the Thailand Research Fund and Mahidol University through the Royal Golden Jubilee Ph.D. Program (Grant No. PHD/0045/2558) to P.W. and C.M.