Induction of Heme Oxygenase-1 Improves Glucose Tolerance and Enhances Insulin Sensitivity in Obese Diabetic Rats

Abstract

Aims: Obesity is a worldwide problem. It is considered to be a major risk factor for many systemic diseases like type 2 diabetes mellitus (T2D), cardiovascular, renal and orthopedic diseases. Recent evidence has underscored the emerging role of the heme oxygenase system in many diseases. The present study was designed to investigate the effects of induction of the HO system by hemin on glucose tolerance and insulin sensitivity in obese diabetic albino rats as an experimental model of T2D. Methodology: 18 male albino rats were divided into three groups: 1- Control group: fed standard pellet chow diet and injected with the vehicle. 2- T2D group: animals were fed high fat diet (HFD) and received single i.p. injection of STZ (35 mg/kg) for induction of diabetes. 3- T2D+Hemin treated group: animals were fed HFD Then, animals received single i.p. injection of STZ (35 mg/kg) for induction of T2D. Hemin (15 mg/kg i.p.) was given twice weekly for 4 weeks after induction of diabetes. Pancreatic tissues and serum were collected and evaluated by Histopathological and biochemical assay for histopatological lesions and biochemical parameters (blood glucose level, insulin level and sensitivity, hemoxygenase activity, lipid peroxides, TNF-α and total anti-oxidant capacity). Results: Pancreatic tissues of diabetic group show severe inflammation with loss of pancreatic architecture, interstitial edema, and marked vacuolization. Hemin therapy preserves pancreatic architecture and reduced the inflammatory lesions and greatly reduced vacuolization in diabetic rats. Hemin treatment decreased the elevated glucose level in diabetic rats from 37.75±2.37 to 22.23±1.69 (mmol/L), lipid peroxides decreased from 22.23±1.69 to1.85±0.24 (µmol/L), TNF- α decreased from 58.95±5.29 to 35.17±3.52 (pg/ml). On the hand hemin treatment increased the total antioxidant activity in diabetic rats from 22.38±2.75 to 70.33±5.29 (µm/mg) and increased insulin level from 3.16±0.48 in diabetic group to 9.21±0.8 (µU/L), hemin treatment also enhanced insulin sensitivity. Conclusion: The results of the present study demonstrated that treatment with hemin induced protection against obesity induced type 2 diabetes most probably by its antioxidant effect and its effect on insulin production and insulin sensitivity. These findings are likely to motivate further research and indicate new approaches for treatment of diabetes.