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Hydrogen sulfide disrupts insulin-induced glucose uptake in L6 skeletal muscle cells

Camila Donoso-Barraza1, Juan Carlos Borquez1, Carlos Sepúlveda1

  • 1Laboratorio de Investigación en Nutrición y Actividad Física (LABINAF), Instituto de Nutrición y Tecnología de Los Alimentos (INTA), Universidad de Chile, Santiago, 7830490, Chile.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|May 16, 2022
PubMed

Insights

Hydrogen sulfide (H2S) production increases during glucose restriction in skeletal muscle cells. This endogenous H2S inhibits insulin-stimulated glucose uptake, independent of the Akt pathway, potentially regulating blood glucose levels.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Endocrinology

Background:

  • Hydrogen sulfide (H2S) is recognized for its toxicity, but endogenous production and physiological roles are increasingly studied.
  • The specific function of H2S in insulin signaling and glucose homeostasis, particularly in skeletal muscle, remains largely undetermined.
  • Skeletal muscle is a critical site for glucose regulation in response to insulin.

Purpose of the Study:

  • To investigate the role of H2S in insulin signaling and glucose uptake within the L6 skeletal muscle cell line.
  • To determine how glucose restriction affects endogenous H2S production and its impact on insulin-mediated glucose transport.

Main Methods:

  • Endogenous H2S synthesis was measured using the fluorescent dye 7-azido-4-methyl coumarin (7-AzMC).
  • The activity of cystathionine γ-lyase (CSE) was assessed using its specific inhibitor, PAG.
  • mRNA levels of CSE were quantified.
  • Insulin-induced glucose uptake was measured following exposure to exogenous H2S.
  • Akt phosphorylation levels were analyzed.

Main Results:

  • Glucose restriction significantly increased endogenous H2S levels in L6 cells.
  • This increase was attributed to stimulated cystathionine γ-lyase (CSE) activity, as inhibition with PAG prevented the rise.
  • mRNA levels of CSE decreased under conditions of glucose and amino acid restriction.
  • Exogenous H2S exposure inhibited insulin-induced glucose uptake for up to 24 hours.
  • The inhibitory effect of H2S on glucose uptake was independent of changes in Akt phosphorylation.

Conclusions:

  • Glucose restriction stimulates endogenous H2S production in skeletal muscle cells, primarily via CSE.
  • H2S negatively impacts insulin-induced glucose uptake in skeletal muscle cells, independent of the Akt signaling pathway.
  • This H2S-mediated antagonism of insulin action may represent a mechanism to maintain plasma glucose levels during hypoglycemia by reducing glucose uptake in skeletal muscle.
Keywords:
Glucose uptakeHydrogen sulfideInsulinNutrient deprivationSkeletal muscle

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