title: Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway.
abstract: Lipotoxicity of pancreatic β-cells is the pathological manifestation of obesity-linked type II diabetes. We intended to determine the cytoprotective effect of kaempferol on pancreatic β-cells undergoing apoptosis in palmitic acid (PA)-stressed condition. The data showed that kaempferol treatment increased cell viability and anti-apoptotic activity in PA-stressed RIN-5F cells and murine pancreatic islets. Furthermore, kaempferol's ability to instigate autophagy was illustrated by MDC-LysoTracker red staining and TEM analysis which corroborated well with the observed increase in LC3 puncta and LC3-II protein expressions along with the concomitant decline in p62 expression. Apart from this, the data showed that kaempferol up/down-regulates AMPK/mTOR phosphorylation respectively. Subsequently, upon inhibition of AMPK phosphorylation by AMPK inhibitors, kaempferol-mediated autophagy was abolished which further led to the decline in β-cell survival. Such observations collectively lead to the conclusion that, kaempferol exerts its cytoprotective role against lipotoxicity by activation of autophagy via AMPK/mTOR pathway.
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India.
authors.forename: Ritu
authors.initials: R
authors.lastname: Varshney
authors.affiliation: College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala 133 207, Haryana, India.
authors.forename: Sumeet
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Molecular Endocrinology Laboratory, Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247 667, Uttarakhand, India. Electronic address: paroyfbs@iitr.ac.in.
authors.forename: Partha
authors.initials: P
authors.lastname: Roy
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D044949:Kaempferols / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008954:Models, Biological; D019308:Palmitic Acid / Q000633:toxicity*; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D044949:Kaempferols; D020011:Protective Agents; D019308:Palmitic Acid; C006552:kaempferol; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK/ mTOR; Apoptosis; Autophagy; Kaempferol; Palmitic acid; Pancreatic β-cell