Insulin promotes glucose consumption via regulation of miR-99a/mTOR/PKM2 pathway

PLoS One. 2013 Jun 10;8(6):e64924. doi: 10.1371/journal.pone.0064924. Print 2013.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cells, Cultured
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Glucose / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Insulin / pharmacology*
  • Lactates / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism
  • Luciferases / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • MicroRNAs / genetics*
  • Phosphorylation
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Thyroid Hormone-Binding Proteins
  • Thyroid Hormones / genetics
  • Thyroid Hormones / metabolism*

Substances

  • Antibiotics, Antineoplastic
  • Carrier Proteins
  • HIF1A protein, human
  • Hypoglycemic Agents
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Insulin
  • Lactates
  • MIRN99 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • Thyroid Hormones
  • Luciferases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Glucose
  • Sirolimus

Grants and funding

This work was supported in part by the National Key Basic Research Program of China (2011CB504003), by National Natural Science Foundation of China (81071642 and 30871296). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.