Cocoa flavonoids attenuate high glucose-induced insulin signalling blockade and modulate glucose uptake and

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Isabel Cordero-Herrera1, María Ángeles Martín2, Luis Goya1

  • 1Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), José Antonio Novais 10, Ciudad Universitaria, 28040 Madrid, Spain.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|November 23, 2013
PubMed

Insights

Cocoa flavanols like (-)-epicatechin (EC) and cocoa polyphenolic extract (CPE) can improve insulin sensitivity. These compounds help regulate glucose metabolism and insulin signaling in liver cells, potentially preventing hepatic dysfunction.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Metabolic Research

Background:

  • Insulin resistance is a hallmark of type 2 diabetes, impacting liver glucose metabolism.
  • The precise mechanisms by which cocoa flavanols prevent hepatic insulin resistance are not fully understood.
  • (-)-epicatechin (EC) and cocoa polyphenolic extract (CPE) show potential antidiabetic effects.

Purpose of the Study:

  • To investigate the preventive effects of EC and CPE on insulin signaling pathways in HepG2 cells.
  • To determine how EC and CPE modulate glucose production and uptake under high glucose conditions.
  • To elucidate the molecular mechanisms underlying the hepatic protective effects of cocoa compounds.

Main Methods:

  • Utilized human HepG2 liver cells treated with high glucose to mimic insulin resistance.
  • Assessed the impact of EC and CPE pre-treatment on key insulin signaling proteins (IR, IRS-1, IRS-2, PI3K/AKT).
  • Measured glucose production, glucose uptake, glycogen content, and AMPK/GLUT-2 levels.

Main Results:

  • EC and CPE pre-treatment restored insulin receptor (IR) and insulin receptor substrate (IRS) levels.
  • These compounds prevented the inactivation of the PI3K/AKT pathway and AMPK.
  • EC and CPE normalized high glucose-induced alterations in glucose production, uptake, and glycogen synthesis.

Conclusions:

  • EC and CPE enhance insulin sensitivity in high glucose-exposed HepG2 cells.
  • Cocoa compounds attenuate insulin signaling blockade and modulate glucose metabolism in the liver.
  • These findings suggest a potential role for cocoa flavanols in preventing hepatic dysfunction associated with diabetes.
Keywords:
(−)-epicatechin2-NBDG2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)5-bromo-2′-deoxyuridine5′-AMP-activated protein kinase7-o-MA7-o-methylaromadendrinAKT/PKBAMPKBrdUCPECa(2+)/calmodulin-dependent protein kinase kinaseCaMMKCocoaECEGCGERKEpicatechinFBSFOXO1G6PaseGLUTGSGSK-3GSPEGlucose productionGlucose uptakeHepG2 cellsIRIRSInsulin signalling pathwayJNKLKB1MAPKPEPCKPI3KPPARPSPPTP-1BT2DMc-Jun N-terminal Kinasecocoa phenolic extractepigallocatechin gallateextracellular regulated kinasefetal bovine serumforkhead box protein O1glucose transporterglucose-6-phosphataseglycogen synthaseglycogen synthase kinase-3grape-seed procyanidin extractinsulin receptorinsulin receptor substrateliver kinase B1mitogen-activated protein kinaseperoxisome proliferator-activated receptorphosphatase 1Bphosphatidylinositol-3-kinasephosphoenolpyruvate carboxykinaseprotein kinase Bpurple sweet potatotype 2 diabetes mellitus

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