Berberine treatment attenuates the palmitate-mediated inhibition of glucose uptake and consumption through increased 1,2,3-triacyl-sn-glycerol synthesis and accumulation in H9c2 cardiomyocytes

Biochim Biophys Acta. 2016 Apr;1861(4):352-62. doi: 10.1016/j.bbalip.2015.12.017. Epub 2016 Jan 7.


Dysfunction of lipid metabolism and accumulation of 1,2-diacyl-sn-glycerol (DAG) may be a key factor in the development of insulin resistance in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid extract that has shown promise as a hypoglycemic agent in the management of diabetes in animal and human studies. However, its mechanism of action is not well understood. To determine the effect of BBR on lipid synthesis and its relationship to insulin resistance in H9c2 cardiomyocytes, we measured neutral lipid and phospholipid synthesis and their relationship to glucose uptake. Compared with controls, BBR treatment stimulated 2-[1,2-(3)H(N)]deoxy-D-glucose uptake and consumption in palmitate-mediated insulin resistant H9c2 cells. The mechanism was though an increase in protein kinase B (AKT) activity and GLUT-4 glucose transporter expression. DAG accumulated in palmitate-mediated insulin resistant H9c2 cells and treatment with BBR reduced this DAG accumulation and increased accumulation of 1,2,3-triacyl-sn-glycerol (TAG) compared to controls. Treatment of palmitate-mediated insulin resistant H9c2 cells with BBR increased [1,3-(3)H]glycerol and [1-(14)C]glucose incorporation into TAG and reduced their incorporation into DAG compared to control. In addition, BBR treatment of these cells increased [1-(14)C]palmitic acid incorporation into TAG and decreased its incorporation into DAG compared to controls. BBR treatment did not alter phosphatidylcholine or phosphatidylethanolamine synthesis. The mechanism for the BBR-mediated decreased precursor incorporation into DAG and increased incorporation into TAG in palmitate-incubated cells was an increase in DAG acyltransferase-2 activity and its expression and a decrease in TAG hydrolysis. Thus, BBR treatment attenuates palmitate-induced reduction in glucose uptake and consumption, in part, through reduction in cellular DAG levels and accumulation of TAG in H9c2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine / pharmacology*
  • Biological Transport
  • Cell Line
  • Diacylglycerol O-Acyltransferase / genetics
  • Diacylglycerol O-Acyltransferase / metabolism
  • Diglycerides / metabolism
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / metabolism
  • Hydrolysis
  • Hypoglycemic Agents / pharmacology*
  • Insulin Resistance
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Palmitic Acid / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Time Factors
  • Triglycerides / biosynthesis*
  • Up-Regulation


  • Diglycerides
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Slc2a4 protein, rat
  • Triglycerides
  • Berberine
  • Palmitic Acid
  • Dgat1 protein, rat
  • Dgat2 protein, rat
  • Diacylglycerol O-Acyltransferase
  • Proto-Oncogene Proteins c-akt
  • Glucose