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Quercetin, a Lead Compound against Type 2 Diabetes Ameliorates Glucose Uptake via AMPK Pathway in Skeletal Muscle

R Dhanya1, A D Arya2, P Nisha1

  • 1Agroprocessing and Technology Division, National Institute for Interdisciplinary Science and Technology, Council of Scientific and Industrial ResearchPappanamcode, India.

Frontiers in Pharmacology
|June 24, 2017
PubMed

Insights

The citrus flavonoid, quercetin, enhances glucose uptake in muscle cells by activating the adenosine monophosphate kinase (AMPK) pathway, not the insulin pathway. This mechanism offers potential for managing type 2 diabetes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cellular Metabolism

Background:

  • Skeletal muscle glucose uptake is critical for metabolic health.
  • Insulin resistance underlies type 2 diabetes, necessitating novel therapeutic targets.
  • Flavonoids, like quercetin, are plant compounds with potential health benefits.

Purpose of the Study:

  • To elucidate the molecular mechanism by which quercetin influences glucose uptake in skeletal muscle cells.
  • To determine if quercetin's effects involve the insulin signaling pathway or alternative mechanisms.
  • To explore quercetin's potential as a therapeutic agent for type 2 diabetes.

Main Methods:

  • Utilized L6 myotubes (skeletal muscle cells) as an in vitro model.
  • Employed protein kinase inhibitors to dissect signaling pathways.
  • Measured 2-NBDG uptake to assess glucose uptake.
  • Analyzed cellular AMP/ATP ratios and mitochondrial membrane potential.
  • Investigated intracellular calcium levels.

Main Results:

  • Quercetin-induced glucose uptake in L6 myotubes is independent of the insulin signaling pathway.
  • Quercetin activates the adenosine monophosphate kinase (AMPK) pathway and its downstream target p38 MAPK.
  • AMPK activation correlates with increased cellular AMP/ATP ratio and altered mitochondrial membrane potential.
  • Quercetin elevates intracellular calcium, suggesting a role for calcium-calmodulin-dependent protein kinase kinase (CaMKK).

Conclusions:

  • Quercetin promotes glucose uptake in skeletal muscle cells via the AMPK/p38 MAPK pathway, bypassing the insulin signaling pathway.
  • The mechanism is similar to that of metformin, suggesting quercetin's potential for type 2 diabetes management.
  • Quercetin may correct insulin resistance by facilitating GLUT4 translocation independently of insulin regulation.
Keywords:
AMPKCaMMKL6 myotubesquercetintype 2 diabetes

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