Hemin Improves Insulin Sensitivity in Skeletal Muscle in High Fat–Fed Mice

Abstract

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 b-oxidation, which was reversed by hemin. Phosphorylated AMPactivated 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.

Modulation of heme oxygenase‐1 expression and activity affects streptozotocin‐induced diabetic nephropathy in rats

“…The current study shows that HM upregulated HO‐1 expression, as well as increased its enzymatic activity in rats having DN, which is in line with previous reports suggesting it as a potent inducer of HO‐1 . Interestingly, in the current study, HM did not significantly increase the activity of HO‐1 in non‐diabetic rats.…”

Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats

“…But it does not affect fatty acid oxidation processes in similar cells extracted from PPAR-a KO mice, which confirms that OEA regulates fatty acid metabolism by activating PPAR-a (13). Obesity and insulin resistance are often accompanied by lipid metabolic disorders (14), which are turned out to be the main cause of NAFLD. As OEA has been demonstrated to induce weight loss in association with improvements in body lipid metabolism, we hypothesize that OEA may play a protective role against NAFLD.…”

Hypoglycemic Activity and the Potential Mechanism of the Flavonoid Rich Extract from Sophora tonkinensis Gagnep. in KK-Ay Mice

“…Because insulin resistance is the main metabolic abnormality of T2DM, there has been considerable interest in insulin-sensitizing agents for the treatment of this disease (Moller, 2001; Ju et al, 2014). One of the most appealing targets for drug development is the insulin-responsive glucose transporter 4 (GLUT4), which is vital to glucose homeostasis (Bryant et al, 2002).…”