Morus alba leaf extract stimulates 5'-AMP-activated protein kinase in isolated rat skeletal muscle

J Ethnopharmacol. 2009 Feb 25;122(1):54-9. doi: 10.1016/j.jep.2008.11.022. Epub 2008 Dec 3.

Abstract

Aim of the study: Morus alba (mulberry) leaf is a natural therapeutic agent that has been shown to have an antidiabetic effect. We explored the possibility that 5'-AMP-activated protein kinase (AMPK) is involved in metabolic enhancement by the Morus alba leaf.

Materials and methods: Isolated rat epitrochlearis muscle was incubated in a buffer containing Morus alba leaf hot water extract (MLE) and the AMPK activation and related events were examined.

Results: In response to MLE treatment, the Thr(172) phosphorylation of the catalytic alpha subunit of AMPK, an essential step for full kinase activation increased in a dose- and time-dependent manner. Ser(79) phosphorylation of acetyl CoA carboxylase, an intracellular substrate of AMPK, increased similarly. Analysis of isoform-specific AMPK activity revealed that MLE activated both the alpha1 and alpha2 isoforms of the catalytic subunit. This increase in enzyme activity was associated with an increased rate of 3-O-methyl-D-glucose transport in the absence of insulin and with phosphorylation of AS160, a signaling intermediary leading to glucose transporter 4 translocation. The intracellular energy status, estimated from the ATP and phosphocreatine concentrations, was not affected by MLE.

Conclusion: MLE stimulates skeletal muscle AMPK activity acutely without changing the intracellular energy status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-O-Methylglucose / metabolism
  • AMP-Activated Protein Kinases / metabolism*
  • Acetyl-CoA Carboxylase / metabolism*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Biological Transport / drug effects
  • Dose-Response Relationship, Drug
  • GTPase-Activating Proteins / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Insulin / metabolism
  • Male
  • Morus* / chemistry
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology
  • Osmolar Concentration
  • Phosphocreatine / metabolism
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Protein Isoforms
  • Rats
  • Rats, Wistar

Substances

  • GTPase-Activating Proteins
  • Glucose Transporter Type 4
  • Insulin
  • Plant Extracts
  • Protein Isoforms
  • TBC1D4 protein, rat
  • Phosphocreatine
  • 3-O-Methylglucose
  • Adenosine Triphosphate
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase