Insulin‐resistance associated hyperinsulinemia activates MEK/ERK signaling and promotes prostatic growth: Reversal of effect with the intervention of PPAR γ agonist pioglitazone

Obesity, dyslipidemia, hyperinsulinemia and insulin‐resistance are the key features of metabolic syndrome and are considered as risk factors for prostatic hyperplasia and type 2 diabetes. The present study was aimed to determine whether or not insulin‐resistance associated hyperinsulinemia contributes to the prostatic hyperplasia. Methods Spargue‐dawley rats were kept on normal‐pellet‐diet/high‐fat‐diet (HFD) for 12 weeks with/without pioglitazone treatment. Effect of diet and pioglitazone was evaluated on the insulin‐sensitivity, lipid‐distribution, cell proliferation and apoptosis. Results Increased cell proliferation, MEK/ERK signaling and alpha‐adrenoceptor mediated contractility was observed in the prostate of insulin‐resistant rats. Pioglitazone treatment led to altered fat distribution, normalization of insulin level and resetting of the cellualr equilibrium in the prostate of HFD‐fed rats. The role of insulin in cellular prliferation was confirmed with insulin‐receptor antagonist S961. Conclusions Diet‐induced hyperinsulinemic condition leads to the increased cellular proliferation, enhanced contractility and enlargement of the prostate in rats. Further, our results suggest that targeting distribution of lipid and insulin signaling could be new objectives for the treatment of prostatic hyperplasia. Source of research support: National Institute of Pharmaceutical Education and Research (NIPER), S.A. S. Nagar, Mohali, Punjab‐160 062, India.