Hemin improves insulin sensitivity in skeletal muscle in high fat-fed mice.

Abstract

The present study examined whether hemin could prevent the development of high-fat diet-induced insulin resistance in the liver and skeletal muscle using a hyperinsulinemic-euglycemic clamp. A four-week high-fat feeding to mice increased the body weight, fat mass, and plasma levels of insulin and lipid, which were reduced by hemin. High-fat diet reduced whole body glucose uptake, which were increased by hemin. Insulin-stimulated hepatic glucose production (HGP) was increased by high-fat diet, but hemin had no significant effect on HGP. Skeletal muscle glucose uptake was reduced by high-fat diet, and hemin normalized the glucose uptake. High-fat diet increased triglyceride levels and mRNA levels of lipogenic enzymes, and decreased mRNA levels of enzymes involved in lipid β-oxidation, which was reversed by hemin. Phosphorylated AMP-activated protein kinase levels were increased in the skeletal muscle of high fat-fed hemin-injected mice. High-fat diet reduced mRNA levels of antioxidant enzymes and increased mRNA levels of inflammatory cytokines and nitrotyrosine levels, which was normalized by hemin in the skeletal muscle. However, hemin had no significant effect on these factors in the liver. These results suggest that hemin prevents the development of high-fat diet-induced insulin resistance by increased insulin sensitivity in the skeletal muscle.

• Authors: Tae-Jin Ju, Woo-Young Kwon, Yong-Woon Kim, Jong-Yeon Kim, Yong-Dae Kim, In-Kyu Lee, So-Young Park
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 126 Issue 2 Pg. 115-25 ( 2014) ISSN: 1347-8648 [Electronic] Japan
• PMID: 25341564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Triglycerides
• 3-nitrotyrosine
• Tyrosine
• Hemin
• Glutathione Peroxidase
• Heme Oxygenase (Decyclizing)
• Superoxide Dismutase
• superoxide dismutase 2
• AMP-Activated Protein Kinases
• Glucose
• Glutathione Peroxidase GPX1
• Gpx1 protein, mouse

Topics

• AMP-Activated Protein Kinases (metabolism)
• Adipose Tissue (metabolism)
• Animals
• Body Weight (drug effects)
• Cytokines (genetics, metabolism)
• Depression, Chemical
• Diet, High-Fat (adverse effects)
• Gene Expression (drug effects)
• Glucose (metabolism)
• Glucose Clamp Technique
• Glutathione Peroxidase (genetics, metabolism)
• Heme Oxygenase (Decyclizing) (genetics, metabolism)
• Hemin (administration & dosage, pharmacology)
• Hyperinsulinism (etiology, prevention & control)
• Hyperlipidemias (prevention & control)
• Insulin Resistance
• Liver (enzymology, metabolism)
• Male
• Mice, Inbred C57BL
• Muscle, Skeletal (metabolism)
• Superoxide Dismutase (genetics, metabolism)
• Triglycerides (metabolism)
• Tyrosine (analogs & derivatives, metabolism)
• Glutathione Peroxidase GPX1