Cod liver oil ameliorates sodium nitrite-induced insulin resistance and degradation of rat hepatic glycogen through inhibition of cAMP/PKA pathway

Life Sci. 2015 Jan 1;120:13-21. doi: 10.1016/j.lfs.2014.11.002. Epub 2014 Nov 11.


Aims: Sodium nitrite is used to inhibit the growth of microorganisms and is responsible for the desirable red color of meat; however, it can be toxic in high quantities for humans and other animals. Moreover, glycogen, a branched polysaccharide, efficiently stores and releases glucose monosaccharides to be accessible for metabolic and synthetic requirements of the cell. Therefore, we examined the impact of dietary sodium nitrite and cod liver oil on liver glycogen.

Main methods: Thirty-two Sprague-Dawley rats were treated daily with sodium nitrite (80 mg/kg) in the presence/absence of cod liver oil (5 ml/kg). Liver sections were stained with Periodic acid-Schiff. Hepatic homogenates were used for measurements of glycogen, cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), glycogen synthase, glycogen synthase kinase, pyruvate carboxylase, fructose 1,6-diphosphatase, glucose 6-phosphatase, phosphodiesterase and glycogen phosphorylase. Glucose, pyruvate tolerances and HOMA insulin resistance were also determined.

Key findings: Sodium nitrite significantly increased plasma glucose and insulin resistance. Moreover, sodium nitrite significantly reduced hepatic glycogen content as well as activities of glycogen synthase, glycogen synthase kinase-3, and phosphodiesterase. Sodium nitrite elevated hepatic cAMP, PKA, pyruvate carboxylase, fructose 1,6-diphosphatase, glucose 6-phosphatase and phosphorylase. Cod liver oil significantly blocked all of these except pyruvate carboxylase, fructose 1,6-diphosphatase and glucose 6-phosphatase.

Significance: Sodium nitrite inhibited liver glycogenesis and enhanced liver glycogenolysis and gluconeogenesis, which is accompanied by hyperglycemia and insulin resistance through the activation of cAMP/PKA and the inhibition of phosphodiesterase. Cod liver oil blocked the sodium nitrite effects on glycogenesis and glycogenolysis without affecting gluconeogenesis.

Keywords: Food additives; Fructose 1,6-diphosphatase; Glycogen phosphorylase; Glycogen synthase; Phosphodiesterase; Pyruvate carboxylase.

MeSH terms

  • Animals
  • Body Weight
  • Cod Liver Oil / chemistry*
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Fructose-Bisphosphatase / metabolism
  • Gluconeogenesis
  • Glycogen Synthase / metabolism
  • Insulin / metabolism
  • Insulin Resistance*
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Liver Glycogen / metabolism*
  • Phosphoric Diester Hydrolases / metabolism
  • Pyruvate Carboxylase / metabolism
  • Pyruvic Acid / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Nitrite / chemistry


  • Insulin
  • Liver Glycogen
  • Cod Liver Oil
  • Pyruvic Acid
  • Cyclic AMP
  • Glycogen Synthase
  • Cyclic AMP-Dependent Protein Kinases
  • Fructose-Bisphosphatase
  • Phosphoric Diester Hydrolases
  • Pyruvate Carboxylase
  • Sodium Nitrite