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Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes
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Carpachromene Ameliorates Insulin Resistance in HepG2 Cells via Modulating IR/IRS1/PI3k/Akt/GSK3/FoxO1 Pathway

Rania Alaaeldin1, Iman A M Abdel-Rahman2, Heba Ali Hassan3

  • 1Department of Biochemistry, Faculty of Pharmacy, Deraya University, Minia 61111, Egypt.

Molecules (Basel, Switzerland)
|December 24, 2021
PubMed

Insights

Carpachromene, a natural compound, enhances glucose metabolism and insulin signaling in liver cells. This study reveals its potential antidiabetic activity by improving insulin receptor function and key metabolic pathways.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Insulin resistance is a key factor in type 2 diabetes and cardiovascular diseases.
  • Carpachromene, a natural compound, is known to inhibit the alpha-glucosidase enzyme.
  • Understanding carpachromene's effects on glucose metabolism and insulin signaling is crucial for developing new antidiabetic therapies.

Purpose of the Study:

  • To investigate the effects of carpachromene on glucose consumption, metabolism, and insulin signaling.
  • To establish and utilize a HepG2 cell model of insulin resistance (HepG2/IRM).
  • To elucidate the molecular mechanisms underlying carpachromene's potential antidiabetic activity.

Main Methods:

  • Established a HepG2 insulin resistant cell model (HepG2/IRM).
  • Assessed cell viability, glucose concentration, and glycogen content following carpachromene treatment.
  • Utilized Western blot analysis to examine key proteins in the insulin signaling pathway (IR, IRS1, PI3K, Akt, GSK3, FoxO1) and measured PEPCK and HK enzyme activities.

Main Results:

  • Carpachromene treatment (6.3-20 µg/mL) showed over 90% cell viability in HepG2/IRM cells.
  • Carpachromene significantly decreased glucose concentration and increased glycogen content in a dose- and time-dependent manner.
  • Carpachromene enhanced insulin receptor signaling by increasing phosphorylated/total ratios of key proteins (IR, IRS1, PI3K, Akt, GSK3, FoxO1), decreased PEPCK activity, and increased HK activity.

Conclusions:

  • Carpachromene demonstrates significant antidiabetic potential by improving glucose metabolism and insulin signaling in an in vitro model.
  • The compound acts centrally on glucose metabolism and insulin signaling through the IR/IRS1/PI3K/Akt/GSK3/FoxO1 pathway.
  • Carpachromene's ability to modulate key components of insulin signaling and glucose metabolism warrants further investigation for therapeutic applications.
Keywords:
HepG2 cellsPI3K/Akt/GSK3/FoxO1 pathwaycarpachromeneinsulin receptorinsulin resistance

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