title: Insulin promotes glucose consumption via regulation of miR-99a/mTOR/PKM2 pathway.
abstract: Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1α and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1α expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1α inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the role and mechanism of insulin in regulating glycolytic activities via miR-99a/mTOR.
authors.affiliation: Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Qiu-Dan
authors.initials: QD
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Yin
authors.forename: Zhu-Mei
authors.initials: ZM
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Liu
authors.forename: Bing-Hua
authors.initials: BH
authors.lastname: Jiang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D005947:Glucose; D007004:Hypoglycemic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D007773:Lactates; D008156:Luciferases; D008565:Membrane Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C497442:HIF1A protein, human; C561679:MIRN99 microRNA, human; C546842:MTOR protein, human